title: Transcriptome-wide mRNA condensation precedes stress granule formation and excludes stress-induced transcripts

status: Public on Apr 26 2024

first: D Allan

last: Drummond

state: IL

address: 929 E 57th Street

institute: University of Chicago

summary: Stress-induced condensation of mRNA and proteins into stress granules is conserved across eukaryotes, yet the function, formation mechanisms, and relation to well-studied conserved transcriptional responses remain largely unresolved. Stress-induced exposure of ribosome-free mRNA following translational shutoff is thought to cause condensation by allowing new multivalent RNA-dependent interactions, with RNA length and associated interaction capacity driving increased condensation. Here we show that, in striking contrast, virtually all mRNA species condense in response to multiple unrelated stresses in budding yeast, length plays a minor role, and instead, stress-induced transcripts are preferentially excluded from condensates, enabling their selective translation. Using both endogenous genes and reporter constructs, we show that translation initiation blockade, rather than resulting ribosome-free RNA, causes condensation. These translation initiation-inhibited condensates (TIICs) are biochemically detectable even when stress granules, defined as microscopically visible foci, are absent or blocked. TIICs occur in unstressed yeast cells, and, during stress, grow before the appearance of visible stress granules. Stress-induced transcripts are excluded from TIICs primarily due to the timing of their expression, rather than their sequence features. Together, our results reveal a simple system by which cells redirect translational activity to newly synthesized transcripts during stress, with broad implications for cellular regulation in changing conditions.

overall_design: S. cerevisiae cells were stressed, and their RNA was fractionated either using Sed-Seq (to identify RNA which sediments in a non-ribosome dependent fashion) or Polysome-Seq (to identify the ribosome association of RNA).

first: Jared

middle: A

last: Bard

first: D

first: Edward

last: Wallace

first: Hendrik

last: Glauninger


title: Multiomic Profile Integration Reveals Early Signatures of Amyotrophic Lateral Sclerosis and Suggests the MAPK Pathway as a Therapeutic Target

status: Public on Apr 22 2024

city: Munich

first: Paul

last: Lingor

address: Ismaninger Str. 22

department: Department of Neurology – Lingor Lab

country: Germany

institute: Rechts der Isar Hospital of the Technical University Munich

type: Non-coding RNA profiling by high throughput sequencing

type: Expression profiling by high throughput sequencing

summary: This SuperSeries is composed of the SubSeries listed below.

overall_design: Refer to individual Series


title: YAP targets TEAD4-NF-κB complex and inhibits ccRCC tumor growth

status: Public on May 31 2024

city: Jinan

first: Tianwei

last: Jia

state: Shandong

address: 天桥区

country: China

institute: Shandong university

type: Genome binding/occupancy profiling by high throughput sequencing

summary: The prevalent understanding of Hippo signaling is one inhibitory pathway in tumor growth via deactivating the potential of YAP-TEAD transcriptional complex. The aberrant activation of YAP was observed in a series of human malignancies. However, recent studies implicate that in certain cancer types, YAP could be a tumor suppressor. Here, we reported a context-dependent function of YAP in clear cell renal carcinoma (ccRCC). Inhibition of Hippo kinase activity impeded ccRCC tumor growth and NF-κB transcriptional programs. Pharmacological blocking Hippo kinase activity or ectopic activation of YAP suppressed tumor growth in xenograft and PDX models. Mechanism studies revealed that TEAD could synchronize with P65 for NF-κB signaling activation, while YAP disrupted TEAD-NF-κB interactions and dissociated P65 from its target gene promoter, thereby inhibiting NF-κB transcriptional programs and ccRCC tumor growth. Our study identified a novel crosstalk between Hippo and NF-κB pathway, uncovered a non-canonical regulation of Hippo/YAP axis in renal cancer and suggested a novel strategy to ccRCC treatments by YAP activation.

overall_design: Chromatin Immunoprecipitation DNA-sequencing  of p65 and TEAD using siTEAD and XMU-MP-1 treatment in 786-O cells

first: Zhongbo

last: Li

first: Miao

last: YU

first: Jian

last: Zhu


title: Multiomic Profile Integration Reveals Early Signatures of Amyotrophic Lateral Sclerosis and Suggests the MAPK Pathway as a Therapeutic Target [miRNA-Seq]

summary: The study conducted a multiomic analysis of the prefrontal cortex from 51 sporadic ALS patients and 50 control subjects, as well as four  transgenic mouse models ( C9orf72, SOD1, TDP-43 and FUS) of ALS with each 5 males/females and 5 case/control samples. The analysis  identified sex-specific differences in early disease mechanisms.

overall_design: Comparative small RNA expression profiling analysis for four transgenic mouse models ( C9orf72, SOD1, TDP-43 and FUS) of ALS with each 5 males/females and 5 case/control samples. For FUS one male control sample was excluded.

first: Lucas

last: Caldi Gomes

first: R

middle: J

last: Pasterkamp

first: Valentina

last: Bonnetto

first: Dieter

last: Edbauer

first: Hubert

last: Rehrauer

first: Ralph

last: Schlapbach

first: Sonja

last: Hänzelmann

first: Stefan

last: Bonn

first: Fabian

last: Hausmann

first: Robin

last: Khatri


title: Transcriptome analysis of murine lung epithelial cells and fibroblasts derived from bleomycin-injured alveolospheres

status: Public on Apr 01 2024

city: Kashiwa

first: BIN

last: WU

state: Chiba

address: #304, 6-6-2, Kashiwanoha

department: Research

country: Japan

institute: ImmunoGeneTeqs

summary: Pulmonary fibrosis is a devatating lung disease with limited effective treatment. Because fibrotic responses are considered to be regulated by complex cellular and molecular circuits, it is difficult to demonstrate a causal relationship of cells, molecules, and cell-cell interactions with diseases in vivo. To overcome this issue, we established bleomycin (BLM)-stimulated alveolosphere model as an ex vivo culture model. To clarify whether our ex vivo model recapitulates the cellular and molecular response to BLM-induced lung injury, we performed RNA-seq (Bulk RNA-seq) analysis of the BLM-stimulated alveolospheres generated by co-culturing murine lung epithelial cells and lung fibroblasts.

overall_design: Alveolopheres were generated by co-culturing primary mouse CD326 positive lung epithelial cells and CD140a positive lung fibroblasts. To clarify transcriptomic changes of BLM-injured alveolospheres,  we stimulated alveolospheres with variant concentration of bleomycin started with 0, 0.01, 0.1, and 1.0 ug/ml in culture media from day 8 to day 10 post co-cultured. After that, bleomycin was removed from the culture media and the alveolospheres were further cultured until day 14 post co-cultured.  Bulk RNA-seq analysis was performed at day 14 post co-cultured.

first: Bin

last: Wu

first: Shigeyuki

last: Shichino

first: Tatsuro

last: Ogawa

first: Rina

last: Matsukiyo

first: Hiroyasu

last: Aoki

first: Satoshi

last: Ueha

first: Kouji

last: Matsushima


title: Inhibition of Notch4 with Novel Neutralizing Antibodies Reduces Tumor Growth in Multiple Tumor Types and Targets Endothelium and Tumor Associated Macrophages in a Mouse Breast Cancer Model  [RiboTag RNA-seq]

status: Public on Aug 08 2024

city: Chicago

first: Jan

middle: K

last: Kitajewski

address: 909 S. Wolcott Ave. MC 901

department: Dept. of Physiology and Biophysics

country: USA

institute: University of Illinois at Chicago

summary: Endothelial Notch signaling is critical for tumor angiogenesis. Notch1 blockade reduces tumor vessel function but causes vascular dysfunction, hypoxia, and gastrointestinal toxicity. Notch4 expression is restricted to developing vasculature, where it promotes angiogenesis. Unlike other Notch proteins, Notch4 has rarely been targeted therapeutically. We developed highly specific Notch4-blocking antibodies, 6-3-A6 and humanized E7011, allowing therapeutic targeting of Notch4 in tumor models. E7011 treatment significantly delayed tumor growth and impaired tumor vessel perfusion in mouse models of breast, skin, and lung tumors. In a mouse orthotopic breast cancer model, Notch4 expression was confined to endothelial cells, but E7011 treatment significantly increased tumor-associated macrophages and increased macrophage expression of anti-tumor genes. Liposomal clodronate-mediated macrophage depletion reversed the anti-tumor effects of E7011, demonstrating that Notch4 supports tumor growth via angiocrine signaling to tumor macrophages. We conclude that targeting Notch4 alters tumor vessel function and tumor associated macrophage phenotype, leading to tumor inhibition.

overall_design: we examined endothelial translatomic changes using the Rpl22tm1.1Psam (RiboTag) system, which isolates cell-type specific polysome-bound mRNA(18), in combination with Cdh5TgCreERT2 to confer endothelial specificity (RiboTagEC mice). RiboTagEC expression was induced with tamoxifen by intraperitoneal injection at 3 weeks old (75mg/kg for 5 days), and orthotopically implanted with Py8119 tumors at 8 weeks. Once tumors reached an average of 50mm3, 6 3 A6 or control IgG was administered as above. Tumors were isolated 10 days after the start of treatment to examine endothelial gene expression changes.

first: Jason

middle: W

last: Eng

first: Yu

last: Kato

first: Yusuke

last: Adachi

first: Bhairavi

last: Swaminathan

first: L

last: Naiche

first: Rahul

last: Vadakath

first: Yoshimasa

last: Sakamoto

first: Youya

last: Nakazawa

first: Sho

first: Ken

last: Ito

first: Takanori

last: Abe

first: Yukinori

last: Minoshima

first: Kana

last: Hoshino-Negishi

first: Hideaki

last: Ogasawara

first: Tomomi

last: Kawakatsu

first: Miyuki

last: Nishimura

first: Masahiko

last: Katayama

first: Masashi

last: Shimizu

first: Kazuhiro

last: Tahara

first: Toshitaka

last: Sato

first: Katsuhisa

last: Suzuki

first: Kishan

last: Agarwala

first: Masao

last: Iwata

first: Kenichi

last: Nomoto

first: Yoichi

last: Ozawa

first: Toshio

last: Imai

first: Yasuhiro

last: Funahashi

first: Junji

last: Matsui


title: Click-chemistry-aided quantitation and sequencing of oxidized guanines and apurinic sites uncovers their transcription-linked strand bias in human cells

status: Public on Jul 21 2024

city: Zurich

first: Shana

last: Sturla

address: Schmelzbergstrasse 9

department: Department of Health Sciences and Technology

country: Switzerland

institute: ETH Zurich

summary: DNA alterations are drivers of aging, neurodegeneration, carcinogenesis, and chemotherapy drug action. To understand the functional genomic roles of DNA modifications, it is critical to accurately map their diverse chemical forms with single-nucleotide precision in complex genomes, which however remains challenging. Click-code-seq is the click-chemistry-aided single-nucleotide-resolution method introduced to map oxidation in yeast DNA. Here, we upgraded click-code-seq to enable its first application for sequencing DNA oxidation and depurination in the human genome. For this, we developed a companion fluorescence tagging assay, click-fluoro-quant, to rapidly quantify common modifications. Moreover, we devised novel adapters to minimize false modification detection and assess modification frequency in cell populations. We uncovered that endogenous DNA oxidation in a human cell line has a highly similar pattern to the cancer mutational signatures associated with the effects of reactive oxygen species. We established that the chemotherapy drug irofulven preferentially depurinates ApA dimers and promoter regions. Intriguingly, we revealed that oxidized guanines and apurinic sites, both irofulven-induced and endogenous, are depleted in the transcribed strand of genes, and the strand bias widens with increasing gene expressions. This work advances click-code-seq for deciphering the impacts of key DNA modifications in the human genome on cellular physiology and toxicological responses.

overall_design: Single-nucleotide-resolution genome-wide mapping click-code-seq of endogenous guanine oxidation in HAP1 wild-type cells in 3 replicates, and of abasic (AP) sites in U2OS wild-type cells that were exposed to 15 µM irofulven (HMAF) in 3 replicates or DMSO (as a control) in 2 replicates.

first: Vakil

last: Takhaveev

first: Nikolai

middle: L

last: Püllen

first: Navnit

last: Singh


title: Association of hepatitis B virus genomes with active chromatin hubs challenges host replication fidelity, leading to DNA damage.

status: Public on Mar 24 2024

city: Madison

first: Kinjal

last: Majumder

state: WI

address: 1525 Linden Drive

department: Oncology

institute: University of Wisconsin

summary: We have developed a modified iteration of a viral chromosome conformation capture (V3C-seq) assay to degrade non-cccDNA to show that the HBV cccDNA localizes spatially with cellular sites of DNA damage.

overall_design: Identification of cellular interaction site of Hepatitis B Virus, and the localization of the resultant DNA damage response. Independent replicates of chromosome conformation capture (designated as V3C in the file name) and ChIP-seq experiments (the target epitope provided in the name) have been performed. For each time-point or treatment, at least two independent replicates of the indicated assays have been performed.

first: Gavin

last: Marcoe


title: Glycolysis in hepatic stellate cells coordinates fibrogenic extracellular vesicle release in a spatial manner to amplify liver fibrosis

status: Public on Mar 20 2024

city: Rochester

first: Yuanhang

last: Liu

state: MN

address: 200 1ST ST SW

institute: Mayo Clinic

summary: Liver fibrosis is characterized by the activation of hepatic stellate cells (HSCs) and the release of fibrogenic nano-sized extracellular vesicles (EVs). Activated HSCs increase their glucose metabolism via glycolysis to satisfy high energy demands. Nevertheless, the mechanism of how glycolysis in HSCs coordinates fibrosis amplification in the fibrogenic zones in the liver is elusive and is the scope of this study. Single cell RNA sequencing (scRNAseq) and bulk RNAseq demonstrated that several glycolysis enzymes, including hexokinase 2 (HK2), were upregulated in activated HSCs. HSC-selective glycolysis-deficient mice (HK2ΔHSC) showed abrogated CCl4-mediated fibrosis as compared to littermate controls (HK2fl/fl). Spatial transcriptomics revealed an upregulation of several EV-related pathways in the fibrotic pericentral zone during liver fibrosis in control HK2fl/fl mice. However, glycolysis-deficient HK2ΔHSC mice showed downregulation of these EV-related pathways in the pericentral zone. Consistently, induction of glycolysis in HSCs in vitro, either by glucose or platelet-derived growth factor B (PDGF), upregulated the expression of several extracellular vesicle (EV)-related genes, including RAB31. Glycolysis in HSCs epigenetically enhanced RAB31 expression through histone-3 lysine-9 acetylation (H3K9ac) on the promoter region, leading to increased EV release. Functionally, glycolysis-dependent EVs were enriched with fibrogenic molecules and increased the expression of fibrotic markers in recipient HSCs. Finally, EVs derived from glycolysis-deficient HK2ΔHSC mice abrogated liver fibrosis amplification as compared to EVs derived from littermate control HK2fl/fl mice. In summary, glycolysis in HSCs amplifies liver fibrosis by promoting fibrogenic EV release in the pericentral fibrotic regions in the liver.

overall_design:
Four mouse liver samples from healthy, fibrotic, and fibrotic with intervention group were analyzed for spatial transcriptomics using Visium platform.
We crossed HK2fl/fl with PDGFRBcreERT2 (The Jackson Laboratory B6.Cg-Tg(Pdgfrb-cre/ERT2)6096Rha/J) mice to obtain PDGFRBcreERT2/Hk2fl/fl mice and HK2fl/fl littermate controls. The genotype of mice S1, S2, and S4 is HK2fl/fl, the genotype of mouse S3 is PDGFRBcreERT2/Hk2fl/fl. All mice were administered with tamoxifen (75 mg/kg for 5 consecutive days). Mouse S1 was treated with olive oil while mice S2, S3, and S4 were treated with CCl4 twice a week for 6 weeks.

first: Enis

last: Kostallari

first: Shalil

last: Khanal


title: Wild type (WT) and Aconitate decarboxylase 1 knockout (Acod1-/-) BMDM treated with Imiquimod for 12h

status: Public on Apr 17 2024

city: Bethesda

first: Kan

last: Jiang

state: MD

address: 9000 Rockville Pike

institute: NIAMS/NIH

summary: The Krebs cycle enzyme Aconitate Decarboxylase 1 (ACOD1) mediates itaconate synthesis in monocytes and macrophages. Here, we explore the role of endogenous ACOD1-itaconate pathway in the activation of BMDM after imiquimod treatment.

overall_design: Female wild type (WT) mice and ACOD1 knockout mice (Acod1-/-) were purchased from Jackson Laboratory (strains JX5304 and JX29340, respectively). Mouse bone marrow cells were flushed out with cold RPMI 1640 medium (Gibco) containing 1% penicillin/streptomycin and were then centrifuged, washed with PBS 1X (Gibco) and filtered through a 70-mm filter mesh. Bone marrow cells were counted and cultured at 1.0 x 106 cells/mL in Dulbecco’s modified Eagle’s medium (DMEM, Thermo Fisher Scientific), supplemented with 10% fetal bovine serum (FBS, Sigma Aldrich), 1% penicillin/streptomycin, and M-CSF 25 ng/mL (R&D). M-CSF was replaced every 2 days. RNA was isolated from BMDM exposed or not, to IMQ for 12 hours. Tri Reagent (Sigma-Aldrich) was used followed by column-based purification with RNA Clean & Concentrator-5 Kit (Zymo Research).

first: Eduardo

last: Patino-Martinez

first: Shuichiro

last: Nakabo

first: Carmelo

last: Carmona-Rivera

first: Luz

middle: P

last: Blanco

first: Mariana

last: Kaplan


title: Transcriptional profiles associated with coronary artery disease in Type 2 diabetes mellitus

status: Public on Mar 01 2024

city: Manila

first: Jana Victoria

last: San Pedro

state: Manila

address: 623 Pedro Gil St.

department: Institute of Human Genetics

country: Philippines

institute: National Institutes of Health

summary:
Coronary artery disease (CAD) is a common complication of Type 2 diabetes mellitus (T2DM). Understanding the pathogenesis of this complication is essential in both diagnosis and management. Thus, this study aimed to characterize the presence of CAD in T2DM using molecular markers and pathway analyses.
Total RNA from peripheral blood mononuclear cells (PBMCs) underwent whole transcriptomic profiling using the Illumina HumanHT-12 v4.0 expression beadchip. Differential gene expression with gene ontogeny analyses was performed, with supporting correlational analyses using weighted correlation network analysis (WGCNA)

overall_design:
The study is a sex- and age-frequency matched case-control design comparing 23 unrelated adult Filipinos with T2DM-CAD to 23 controls (DM with CAD). The experiment used two microarray platforms to generate the data used for the published article (PMID: 38706700). The data from these platforms were merged and then analyzed. One of the platforms, Illumina, was used on 56 samples (Healthy n=15, DM with no CAD n=21, DM with CAD n=20), while the platform Affymatrix was used on 13 samples (Healthy n=8, DM with no CAD n=2, DM with CAD n=3).

UPDATE: [Sept-24-2025]
Sample 'sample group':
"DM" changed to "DMCAD" (DM with CAD)
"no DM" changed to "DMnoCAD" (DM with no CAD)
Sample 'comorbidity':
'with Retinopathy" changed to "with CAD"
'with no Retinopathy" changed to "with no CAD"
'healthy" changed to "NA"

first: Jose

middle: B

last: Nevado Jr.

first: Elizabeth

middle: T

last: Paz-Pacheco

first: Aimee

middle: Y

last: Aman

first: Christian

middle: D

last: Deguit

first: Mark

last: Francisco


title: Transcriptome-wide analysis of CRISPR-edited iPSC-derived glioma models

status: Public on May 15 2024

first: Xiao

last: Song

address: 303 E Superior St, Lurie 6-250

department: Neurology

institute: Northwestern University Feinberg School of Medicine

summary: CRISPR-edited human induced pluripotent stem cell (iPSC)-derived glioma models provide a robust platform to investigate the biology of these aggressive tumors in an isogenic background or to test possible treatments in preclinical settings. We created iPSC12 lines that carry different combinations of glioma driver mutations using CRISPR/Cas9 genome editing technology, including TP53-/-, ATRX-/-, IDH1-R132H/WT, PTEN-/-, CDKN2A/B-/-, TERT promoter(TERTp) C228T/WT, MTAP-/-, and overexpression (OE) of EGFRvIII oncogenic isoform. Edited iPSCs were then differentiated into neural progenitor cells (NPC) using a small molecule protocol. We cultured the edited NPCs in 3D organoid with an FBS-containing differentiation medium. After 14 days, different genotypes of NPCs formed organoids were harvest and RNAs were isolated and subjected to RNA-seq analysis. To create an in vivo model system, NPCs with different genotypes were intracranially transplanted into athymic mice. Mice were sacrificed when pathologic symptoms developed resulting from tumor burden or 120 days post brain transplantation. RNAs were extracted from the tumor region of brain tissue sections and subjected to RNA-seq analysis. Our study showed that the iPSC-based model of gliomas displayed distinct mutation-dependent variation in transcriptome, which recapitulated the gene expression signatures of human gliomas.

sample_organism:
Homo sapiens
Homo sapiens/Mus musculus xenograft

overall_design: Gene expression and alternative splicing profiling analysis of CRISPR-edited iPSC-derived glioma models in vitro and in vivo. Samples include in vitro organoids of NPCs with genotypes of T (TP53-/-), TA (TP53-/-, ATRX-/-), TI (TP53-/-, IDH1-R132H/WT), TIA (TP53-/-, IDH1-R132H/WT, ATRX-/-), PCT (PTEN-/-, CDKN2A/B-/-, TERTp-C228T/WT), PCTM (PTEN-/-, CDKN2A/B-/-, TERTp-C228T/WT, MTAP-/-), PCTE (PTEN-/-, CDKN2A/B-/-, TERTp-C228T/WT, EGFRvIII-OE), and PCTME (PTEN-/-, CDKN2A/B-/-, TERTp-C228T/WT, MTAP-/-, EGFRvIII), as well as in vivo xenografts (triplicates of each genotypes) from NPC-TI, TIA, PCTE, and PCTME.

first: Shunichiro

last: Miki

first: Frank

middle: F

last: Furnari

first: Shi-Yuan

last: Cheng


title: Evaluation of the impact of scFv on functionality and safety of 3rd generation CD123 CAR T cells

status: Public on Jun 03 2024

city: Besancon

first: Evan

last: Seffar

address: 8 rue du Dr JFX Girod

country: France

institute: UMR INSERM 1098

summary: Chimeric Antigen Receptor T cells express an extracellular domain consisting of a single-chain fragment variable (scFv) targeting a surface tumor-associated antigen (TAA), it is important to select scFv regarding safety profile through evaluation of the efficacy/toxicity balance, especially in cases where the target antigen is also expressed on healthy cells. Here, we developed five CAR T cells targeting CD123 (CD123 CAR-T) by substituting only the scFv, looking for differences in terms of efficacy and on-target/off-tumor effects. Using in vitro models, we found that three of the five CD123 CAR-T were more cytotoxic against leukemic cells, without increasing lysis of monocytes or endothelial cells. Using the Incucyte system, we confirmed the low cytotoxicity of CD123 CAR-T on endothelial cells. Hematotoxicity evaluated by progenitor culture and CD34 cell lysis showed that two of the five CD123 CAR-T were less cytotoxic against HSC, and we confirmed in a humanized mouse model that CD123- cells were not eliminated by the CD123 CAR-T. These two CD123 CAR-T reduced tumor infiltration and increased overall survival of mice in three in vivo models of BPDCN. Moreover, in BPDCN aggressive model, bulk RNA-sequencing analysis showed that these CD123 CAR-T upregulated genes associated with cytotoxicity and activation/exhaustion a few days after the injection. Finally, we were able to produce CD123 CAR-T selected previously from patient T cells. Together, these results emphasize the importance of screening different scFv for the development of CAR-T constructs, to select the one with the optimal risk-benefit ratio for clinical development.

overall_design: To assess the impact of scFv on the in vivo functionality of CD123 CAR-T, we sorted CD123 CAR-T injected into mice (hCD45/hCD3/hCD19) in the peripheral blood.

first: Maxime

last: Fredon

first: Florian

last: Renosi

first: Romain

last: Boidot

first: Sandrine

last: Chevrier

first: Francine

last: Garnache-Ottou


title: Gene-specific RNA homeostasis revealed by perturbation of the NuA4/Tip60 acetyltransferase complex

status: Public on Jan 30 2024

city: Illkirch

first: Manuel

last: Mendoza

address: 1 rue Laurent Fries

institute: INSTITUTE OF GENETICS AND MOLECULAR AND CELLULAR BIOLOGY


title: Cytidine deaminase resolves replicative stress and protects pancreatic cancer from DNA-targeting drugs I

status: Public on Jan 24 2024

city: Toulouse

first: Pierre

last: Cordelier

address: 2, avenue Hubert Curien

institute: Cancer Research Center of Toulouse

summary: Cytidine deaminase (CDA) functions in the pyrimidine salvage pathway for DNA and RNA synthesis and has been shown to protect cancer cells from deoxycytidine-based chemotherapies. In this study, we observed that CDA was overexpressed in pancreatic adenocarcinoma from patients at baseline and was essential for experimental tumor growth. Mechanistic investigations revealed that CDA localized to replication forks where it increased replication speed, improved replication fork restart efficiency, reduced endogenous replication stress, minimized DNA breaks, and regulated genetic stability during DNA replication. In cellular pancreatic cancer models, high CDA expression correlated with resistance to DNA-damaging agents. Silencing CDA in patient-derived primary cultures in vitro and in orthotopic xenografts in vivo increased replication stress and sensitized pancreatic adenocarcinoma cells to oxaliplatin. This study sheds light on the role of CDA in pancreatic adenocarcinoma, offering insights into how this tumor type modulates replication stress. These findings suggest that CDA expression could potentially predict therapeutic efficacy and that targeting CDA induces intolerable levels of replication stress in cancer cells, particularly when combined with DNA-targeted therapies

overall_design: To explore the consequences of cytidine deaminase (CDA) targeting or overexpression in human panceratic cancer cells Mia PACA-2

first: Audrey

last: Lumeau


title: Multiomic Profile Integration Reveals Early Signatures of Amyotrophic Lateral Sclerosis and Suggests the MAPK Pathway as a Therapeutic Target [RNA-Seq]

first: Paul

last: Lingor

overall_design: Comparative gene expression profiling analysis of RNA-seq data for four  transgenic mouse models ( C9orf72, SOD1, TDP-43 and FUS) of ALS with each 5 males/females and 5 case/control samples. For FUS one male control sample was excluded.

first: Lucas

last: Caldi Gomes

first: R

last: Pasterkamp

first: Valentina

last: Bonnetto

first: Dieter

last: Edbauer

first: Hubert

last: Rehrauer

first: Ralph

last: Schlapbach

first: Sonja

last: Hänzelmann

first: Stefan

last: Bonn

first: Fabian

last: Hausmann

first: Robin

last: Khatri


title: Brain–muscle tissue communication prevents muscle aging by maintaining daily physiology

status: Public on Feb 01 2024

city: Barcelona

first: Eusebio

last: Perdiguero

address: Dr. Aiguader 88

department: Department of Medicine and Life Sciences

country: Spain

institute: UPF

summary: The muscle peripheral clock selects, suppresses, and integrates signals from the central clock that serve muscle homeostasis, thus revealing its critical gatekeeper function.

overall_design: Four biological replicates (2 males and 2 females, if not otherwise specified) at each zeitgeber time (ZT) point were used to collect RNA samples from the snap-frozen tibialis anterior muscle. A total of 360 mouse RNA samples were sequenced to generate the circadian RNA transcriptome. Eight samples were excluded from analysis due to quality issues.

first: Arun

last: Kumar

first: Mireia

last: Vaca-Dempere

first: Oleg

last: Deryagin

first: Pura

last: Munoz-Canoves


title: Intra-tumoral T cells in pediatric brain tumors display clonal expansion and effector properties

status: Public on Jan 16 2024

city: San Diego

first: Pandurangan

last: Vijayanand

state: California

address: 9420 Athena Cir, La Jolla

department: Vaccine Discovery

institute: La Jolla Institute for Immunology

summary: T cell responses within pediatric brain tumors (PBT) remain poorly understood. We performed single-cell RNA-seq (scRNA-seq) and paired T cell receptor sequencing (TCR-Seq) of patient-derived brain tumor-infiltrating T cells to map T cell molecular profile with TCR repertoire and clonality. We demonstrate marked clonal expansion of intra-tumoral T cells and reveal their differential phenotype, transcriptional state and functional properties within brain tumors. To understand T cell responses within highly immunogenic tumors that respond to checkpoint blockers, we undertook analysis of human non-small cell lung cancer (NSCLC). We performed single-cell RNA-seq (scRNA-seq) and paired T cell receptor sequencing (TCR-Seq) of patient-derived lung tumor-infiltrating T cells to map T cell molecular profile with clonality.

overall_design: PBT: Tumor samples were obtained from pediatric patients with brain tumors. Tumor samples were disintegrated and cells from each donor were labelled with dead cell discriminating dye, fluorophore-tagged FACS antibodies and unique anti-human hashtag antibodies against beta2 microglobulin for donor deconvolution. T cells from each donor were FACS-sorted for scRNA-seq using the 10X genomics platform. Experiments were performed on five separate experimental days (5 batches). Two libraries of pooled, live, singlet-gated, CD45+CD3+ T cells were generated from each of the first 3 experiments. And two libraries of pooled, live, singlet-gated cells (one of CD8+ T cells and another of CD4+ T cells), were generated from each of the last 2 experiments. NSCLC: Tumor samples were obtained from 10 patients with non-small cell lung cancer. Tumor samples were disintegrated and cells from each donor were labelled with dead cell discriminating dye, fluorophore-tagged FACS antibodies and unique anti-human hashtag antibodies against beta2 microglobulin for donor deconvolution. T cells from each donor were FACS-sorted for scRNA-seq using the 10X genomics platform. Two and four libraries of pooled, live, singlet-gated, CD45+CD3+CD4+ T cells and CD45+CD3+CD8+ T cells were generated respectively from the 10 donors.

first: Aditi

last: Upadhye

first: Kevin

middle: E

last: Meza Landeros

first: Ciro

last: Ramírez-Suástegui

first: Benjamin

last: Schmiedel

first: Edwin

last: Woo

first: Denise

last: Malicki

first: Nicole

last: Coufal

first: David

last: Gonda

first: Michael

last: Levy

first: Jason

last: Greenbaum

first: Gregory

last: Seumois

first: John

last: Crawford

first: William

last: Roberts

first: Stephen

last: Schoenberger

first: Christian

last: Ottensmeier

first: Anusha

last: Ganesan


title: Cytidine deaminase resolves replicative stress and protects pancreatic cancer from DNA-targeting drugs II

first: Pierre

last: Cordelier

first: Audrey

last: Lumeau


title: YAP targets TEAD-NF-κB complex and inhibits ccRCC tumor growth

status: Public on Dec 31 2023

first: Tianwei

last: Jia

overall_design: Chromatin immunoprecipitation DNA-sequencing(ChIP-seq) for histone modification H3K27ac and transcription factor TEAD in 786-O cells.

first: Jian

last: Zhu

first: Haiyang

last: Guo

first: Yaning

last: Xu


title: Circulating NK cells establish tissue-residency upon acute infection of skin and mediate accelerated effector responses to secondary infection

status: Public on Dec 28 2023

city: Wuerzburg

first: Georg

last: Gasteiger

address: Versbacher Strasse 9

department: Institute of Systems Immunology

institute: University Wuerzburg

summary:
Natural killer (NK) cells are present in the circulation and can also be found residing in
tissues; these populations exhibit distinct developmental requirements and are thought
to differ in terms of ontogeny. Here, we investigated whether circulating conventional
NK (cNK) cells can develop into long-lived, tissue-resident cells following acute
infections. We found that viral and bacterial infections of the skin triggered the
recruitment of cNK cells and their differentiation into Tcf1hiCD69hi tissue-resident
(trNK) cells that share transcriptional similarity with CD56brightTCF1hi NK cells in
human tissues. Skin trNK arose from IFN-g-producing effector cells and required
restricted expression of the transcriptional regulator Blimp1 to optimize Tcf1-dependent
trNK formation. Upon secondary infection, trNK cells rapidly gained effector function
and mediated an accelerated NK cell response. Thus, cNK cells redistribute and
permanently position at sites of previous infection via a mechanism promoting tissueresidency
that is distinct from Hobit-dependent developmental paths of NK cells and
ILC1 seeding tissues during ontogeny

overall_design:
scRNA-seq, cell hashing and CITE-seq. ILC1s and NK cells were sorted as individual, hash-tagged populations before pooling into one reaction. Before sorting, cells were labeled with oligonucleotide-tagged antibodies for cellular indexing of transcriptomes and epitopes by sequencing (CITE-Seq).
List of Hashtags and CITE seq antibody used: Ms.Hashtag_1 ACCCACCAGTAAGAC, Ms.Hashtag_2 GGTCGAGAGCATTCA, Ms.Hashtag_3 CTTGCCGCATGTCAT, Ms.Hashtag_4 AAAGCATTCTTCACG, Ms.Hashtag_5 CTTTGTCTTTGTGAG. HuMs.CD11b TGAAGGCTCATTTGT, Ms.CD45 TGGCTATGGAGCAGA, Ms.CD45.2 CACCGTCATTCAACC, HuMsRt.CD27 CAAGGTATGTCACTG, Ms.CD69 TTGTATTCCGCCATT, Ms.CD127 GTGTGAGGCACTCTT, Ms.CD103 TTCATTAGCCCGCTG, HuMs.KLRG1 GTAGTAGGCTAGACC, Ms.CD49b CGCGTTAGTAGAGTC, Ms.Ly49H CCAGTAGGCTTATTA. We multiplexed Skin d8 with hashtag_1, Skin d25 with hashtag_2, Salivary Gland d25 with hashtag_3, Spleen d8 with hashtag_4, and Spleen d25 with hashtag_5.

first: Tommaso

last: Torcellan

first: Christin

last: Friedrich

first: Rémi

last: Doucet-Ladevèze

first: Thomas

last: Ossner

first: Virgínia

last: Visaconill Solé

first: Sofie

last: Riedmann

first: Milas

last: Ugur

first: Stephan

last: Rosshart

first: Sebastian

last: Arnold

first: Mercedes

last: Gomez de Agüero

first: Nicola

last: Gagliani

first: Richard

last: Flavell

first: Simone

last: Backes

first: Wolfgang

last: Kastenmueller


title: MPRA from K562 (ENCSR909JVP)

status: Public on May 07 2024

city: Stanford

first: ENCODE

last: DCC

state: CA

address: 300 Pasteur Dr

institute: ENCODE DCC

summary: For data usage terms and conditions, please refer to http://www.genome.gov/27528022 and http://www.genome.gov/Pages/Research/ENCODE/ENCODE_Data_Use_Policy_for_External_Users_03-07-14.pdf


title: Estradiol-mediated enhancement of the human ectocervical epithelial barrier correlates with desmoglein-1 expression in the follicular menstrual phase

status: Public on Jan 17 2025

city: Stockholm

first: Kristina

last: Broliden

state: Solna

address: Visionsgatan 4, J7:20

department: Dept. of Medicine Solna

country: Sweden

institute: Karolinska Institutet

summary: Introduction: Structural integrity of the cervical epithelial barrier is crucial for defending the female reproductive tract against sexually transmitted infections, including HIV. Female sex hormones, estradiol and progesterone, play an important role in modulating this epithelial barrier. However, the influence of fluctuating estradiol and progesterone on ectocervical tissue gene and protein expression in naturally cycling women at high risk for sexually transmitted infections is not well understood. Methods: Ectocervical biopsies, cervicovaginal lavage fluid, and venous blood samples were collected from naturally cycling Kenyan female sex workers at two time points, separated by 2 weeks. The first time point represented the luteal phase of the menstrual cycle and the second time point represented the follicular phase. Plasma estradiol and progesterone levels were measured at each time point. Ectocervical tissues were analyzed by RNA-sequencing and in situ immunofluorescence staining. Cervicovaginal lavage samples were evaluated using antibody-based protein profiling. Results: Employing a systems biology approach, we demonstrated that high plasma estradiol levels enhanced ectocervical epithelial integrity. These findings were more pronounced in samples from the follicular phase (when progesterone and estradiol levels were significantly lower) and included increased expression, and more intact distribution, of the desmosomal cadherin DSG1. The effects of progesterone on gene and protein levels, as well as on intact tissue (as visualized by in situ staining), were modest throughout the menstrual cycle. Both estradiol and progesterone levels had limited influence on mucosal immune factors. Conclusion: Estradiol levels were associated with modulation of cervical epithelial barrier integrity, including the expression and distribution of DSG1, during the follicular phase of natural menstrual cycles in Kenyan sex workers.

overall_design:
In this study we correlated gene expression with plasma estradiol and progesterone at two time points in the menstrual cycle. Ectocervical tissue were obtained from Kenyan female sex workers, the first sample was obtained during the luteal phase (n=58), and the second sample was obtained during the follicular phase (n=66) of the menstrual cycle (Table 1).  RNA used for sequencing was extracted from the ectocervical biopsies. The data from the follicular phase can be accessed at Omnibus public repository, SuperSeries ID GSE217237.

The records represent total 113 Luteal samples.

The counts-norm-LUT.n=58.csv contains the normalized data for the selected 58 Luteal samples.

The counts-norm-FOL.n=66.csv contains the normalized data for the re-analyzed 64 samples from GSE183513:
GSM5558523, GSM5558524, GSM5558525, GSM5558526, GSM5558527, GSM5558528, GSM5558529, GSM5558530, GSM5558531, GSM5558532, GSM5558533, GSM5558534, GSM5558535, GSM5558536, GSM5558537, GSM5558538, GSM5558539, GSM5558540, GSM5558541, GSM5558542, GSM5558543, GSM5558544, GSM5558545, GSM5558546, GSM5558547, GSM5558548, GSM5558549, GSM5558550, GSM5558551, GSM5558552, GSM5558553, GSM5558554, GSM5558555, GSM5558556, GSM5558557, GSM5558558, GSM5558559, GSM5558560, GSM5558561, GSM5558562, GSM5558563, GSM5558564, GSM5558565, GSM5558566, GSM5558567, GSM5558568, GSM5558569, GSM5558570, GSM5558571, GSM5558572, GSM5558573, GSM5558574, GSM5558575, GSM5558576, GSM5558577, GSM5558578, GSM5558579, GSM5558580, GSM5558581, GSM5558582, GSM5558583, GSM5558584, GSM5558585, GSM5558586
and two (GSM8436015, GSM8436014) samples from the GSE194276 records

*** Submitters state that the raw sequencing data from the study participants cannot be held in a public repository due to the sensitive nature of such personal data***


title: Single-nucleus transcriptomic highlights sex differences in cardiac molecular signaling and identifies a novel cardiomyocyte population associated with CCNA2-mediated cardiac regeneration

status: Public on Dec 06 2023

city: New York

first: Hina

last: Chaudhry

state: USA

department: Cardiology

institute: Mount Sinai Hospital

summary: Adult mammalian hearts lack regenerative potential and this is a significant contributing cause of the extensive morbidity and mortality of cardiovascular disease.  We performed single nucleus RNA sequencing (snRNA-seq) to capture of cell diversity and gender-specific changes as well as identification of critical differentially expressed genes in cellular clusters throughout the heart.

overall_design: Adult hearts isolated from female and male normal wild-type (both nontransgenic-nTG and CCNA2 constitutively expressing-Transgenic-Tg) mice.

last: chaudhry

first: Prabhu

last: Mathiyalagan

first: Esmaa

last: Bouhamida

first: Sangeetha

last: Vaddake-Madathil


title: IDH1-mutant preleukemic hematopoietic stem cells can be eliminated by oxphos inhibition

status: Public on Nov 30 2023

first: Niklas

last: Landberg

address: 265 Campus Dr Stanford

department: Institute for Stem Cell Biology and Regenerative Medicine

institute: Stanford University

summary: Rare preleukemic hematopoietic stem cells (pHSCs) harboring only the initiating mutations can be detected at the time of AML diagnosis. pHSCs are likely the origin of leukemia and a potential reservoir for relapse but remain challenging to eradicate. Using primary human samples and gene-editing to model isocitrate dehydrogenase 1 (IDH1) mutant pHSCs, we show biological, transcriptional, and metabolic differences between pHSCs and healthy hematopoietic stem cells (HSCs). We confirm that IDH1 mutations are present in patients with clonal cytopenia of undetermined significance, but not in individuals with clonal hematopoiesis of indeterminate potential, suggesting an inherent defect to fully reconstitute hematopoiesis. Despite giving rise to multilineage engraftment, IDH1-mutant pHSCs exhibited reduced proliferation with a block in differentiation, downregulation of MHC Class II genes and reprogramming of oxphos metabolism. Critically, IDH1-mutant pHSCs showed reduced metabolic activity distinct from normal HSCs and inhibition of oxphos resulted in complete eradication of IDH1-mutant pHSCs but not IDH2-mutant pHSCs or wildtype HSCs. Our results indicate that IDH1-mutant preleukemic clones can be targeted with complex I inhibitors to prevent development and relapse of leukemia.

overall_design: Human cord blood derived HSPCs from four donors were genetically engineered to expressed wildtype or mutant IDH1 or IDH2 and an AAVS1 GFP only control and subjected to RNA sequencing.

first: Ravindra

last: Majeti


title: Deep RNA-Seq of Human Fetal and Adult Heart

status: Public on Feb 27 2024

summary: The objective of this dataset was to employ RNA sequencing (RNA-seq) on human fetal and adult heart tissues to elucidate the reprogramming genes targeted by CCNA2-induced cytokinesis.

overall_design: We performed a comparative gene expression profiling analysis of deep RNA-seq ofhuman fetal and adult hearts.

first: Jessica

last: Wang


title: Epigenetic array data of saliva samples in individiduals with esophageal cancer with controls

status: Public on Feb 07 2024

city: London

first: Laurence

middle: Bruce

last: Lovat

address: 43-45 Foley Street

department: Division of Surgery & Interventional Science

country: United Kingdom

institute: University College London

summary: We took saliva samples from 89 people with oesophageal cancer (plus 9 with high grade dysplasia, also labelled here as cancer) and 167 controls. We took replicate samples on 6 cancer samples and 4 controls to assess reproducibility. The cancer groups comprise people with invasive adenocarcinoma (61 and also 6 replicates), 28 people with intramucosal adenocarcinoma, 9 people with high-grade dysplasia arising in Barrett's esophagus, 52 patients with non-dysplastic Barrett's esophagus, 42 people with no positive diagnosis after endoscopy (ie no Barrett's, + 1 replicate), and 73 self-reported healthy volunteers (with 3 duplicates)

overall_design: The principle design was a two group case-control study

first: Timothy

middle: C

last: Stone


first: Georg

last: Gasteiger

summary:
Natural killer (NK) cells are present in the circulation and can also be found residing in
tissues; these populations exhibit distinct developmental requirements and are thought
to differ in terms of ontogeny. Here, we investigated whether circulating conventional
NK (cNK) cells can develop into long-lived, tissue-resident cells following acute
infections. We found that viral and bacterial infections of the skin triggered the
recruitment of cNK cells and their differentiation into Tcf1hiCD69hi tissue-resident (trNK)
cells that share transcriptional similarity with CD56brightTCF1hi NK cells in human
tissues. Skin trNK arose from IFN--producing effector cells and required restricted
expression of the transcriptional regulator Blimp1 to optimize Tcf1-dependent trNK
formation. Upon secondary infection, trNK cells rapidly gained effector function and
mediated an accelerated NK cell response. Thus, cNK cells redistribute and
permanently position at sites of previous infection via a mechanism promoting tissueresidency
that is distinct from Hobit-dependent developmental paths of NK cells and
ILC1 seeding tissues during ontogeny.

overall_design:
Group 1 ILCs from spleen, blood and skin were sorted from naive or VACV acutely infected or rechallenged mice.

List of Hashtags and Cite seq antibodies used in this study: Hashtag2_TotalA GGTCGAGAGCATTCA, Hashtag3_TotalA CTTGCCGCATGTCAT, Hashtag4_TotalA AAAGCATTCTTCACG, Hashtag5_TotalA CTTTGTCTTTGTGAG, Hashtag6_TotalA TATGCTGCCACGGTA. CD45_TotalA TGGCTATGGAGCAGA, CD45.1_TotalA CCTATGGACTTGGAC, CD45.2_TotalA CACCGTCATTCAACC, CD11b_TotalA TGAAGGCTCATTTGT, CD25_TotalA ACCATGAGACACAGT, CD27_TotalA CAAGGTATGTCACTG, CD49a_TotalA CCATTCATTTGTGGC, CD49b_TotalA CGCGTTAGTAGAGTC, CD62L_TotalA TGGGCCTAAGTCATC, CD69_TotalA TTGTATTCCGCCATT, CD127_TotalA GTGTGAGGCACTCTT, CD160_TotalA GCGTATGTCAGTACC, CD200r_TotalA ATTCTTTCCCTCTGT, CX3CR1_TotalA CACTCTCAGTCCTAT, Cxcr6_TotalA TGTCAGGTTGTATTC, KLRG1_TotalA GTAGTAGGCTAGACC, NK1.1_TotalA GTAACATTACTCGTC, NKp46_TotalA CCCTTTCACCTCGAA.
We multiplexed mem rechall skin with Hashtag_2, mem ctrl skin with Hashtag_3, naïve chall skin with Hashtag_4, naïve ctrl spleen with Hashtag_5, and naïve ctrl blood with Hashtag_6.

first: Tommaso

last: Torcellan

first: Christin

last: Friedrich

first: Rémi

last: Doucet-Ladevèze

first: Thomas

last: Ossner

first: Virgínia

last: Visaconill Solé

first: Sofie

last: Riedmann

first: Milas

last: Ugur

first: Fabian

last: Imdahl

first: Stephan

last: Rosshart

first: Sebastian

last: Arnold

last: Gomez de Agüero

last: Kastenmüller


title: ROS-induced translation impairment underlies ZAK-mediated metabolic decline in obesity and aging

status: Public on Oct 23 2023

city: Lausanne

first: David

last: Gatfield

address: Genopode building

department: Center for Integrative Genomics

institute: University of Lausanne

summary: The ribotoxic stress response (RSR) denotes a signaling pathway in which the p38 and JNK-activating MAP3 kinase ZAK senses stalling and/or collision of ribosomes with unknown physiological implications. Here, we show that reactive oxygen species (ROS)-generating agents robustly trigger translational impairment and ZAK activation. As a testament to the physiological importance of this signaling pathway, zebrafish larvae deficient for the ZAK kinase are protected from ROS-induced pathology and death. Furthermore, livers of mice fed a ROS-generating and obesogenic diet accrue ZAK-activating and antioxidant-reversed ribosomal stalls and collisions. Highlighting a role for the RSR in metabolic regulation, ZAK knockout (KO) mice are protected from developing insulin resistance and liver steatosis under these conditions. Finally, aged chow-fed ZAK KO mice do not display the normal hallmarks of metabolic aging. In sum, our work highlights ROS-induced translational impairment as a physiological activation signal for ZAK that underlies metabolic adaptation in obesity and aging.

overall_design: Comparative ribosome and disome footprints of DISOME-seq (PD) and RIBO-seq (PF) data of mouse livers tissues grown in standard diet and high fat diet

first: Goda

last: Snieckute

first: Laura

last: Ryder

first: Anna

last: Constance Vind

first: Zhenzhen

last: Wu

first: Frederic

last: Schrøder Arendrup

first: Mark

last: Stoneley

first: Sébastien

last: Chamois

first: Marion

last: Leleu

first: René

last: Dreos

first: Alexander

last: Russell

first: Aitana

last: Victoria Genzor

first: Astrid

last: Linde Basse

first: Morten

last: Dall

first: Lucile

last: Chantal Marie Dollet

first: Melanie

last: Blasius

first: Anne

last: Willis

first: Anders

middle: H

last: Lund

first: Jonas

last: Thue Treebak

first: Steen

last: Seier Poulsen

first: Betsy

last: Pownall

first: Christoffer

last: Clemmensen

first: Zach

last: Gerhart-Hines

first: Simon

last: Bekker-Jensen


title: Inhibiting neddylation with MLN4924 potentiates hypoxia-induced apoptosis of mouse type B spermatogonia GC-2 cells

status: Public on Nov 02 2023

city: Wuhan

first: Hongyan

last: Deng

state: Hubei

address: No. 7 Donghu South Road, Wuchang District

institute: Institute of Hydrobiology, Chinese Academy of Sciences

summary: Hypoxia, an inadequate supply of tissue oxygen tension, has been reported to induce apoptosis of spermatogenic cells and is associated with male infertility. Neddylation, a post-translational modification similar to ubiquitination, has been shown to be involved in the hypoxia stress response. However, the functions of neddylation in hypoxia-induced apoptosis of spermatogenic cells and its association with male infertility remain largely unexplored. In this study, aiming to explore the role of neddylation in male infertility, we used the specific neddylation inhibitor MLN4924 for treatment in mouse type B spermatogonia GC-2 cells. Our results showed that MLN4924 had no apparent effect on GC-2 cell apoptosis under normoxia, but significantly increased apoptotic cells under hypoxia. Transcriptomic analysis and qPCR assay confirmed that MLN4924 could suppress the expression of hypoxia target genes in GC-2 cells under hypoxia. In addition, MLN4924 could enhance the induction of intracellular and mitochondrial reactive oxygen species (ROS) under hypoxia. These results indicate that the neddylation inhibitor MLN4924 potentiates hypoxia-induced apoptosis of mouse type B spermatogonia GC-2 cells, and neddylation may play an important role in promoting spermatogenic cells to adapt to hypoxia stress.

overall_design: GC-2 cells were incubated with MLN4924 (1 μM) or DMSO as control, and then the cells were cultured under normoxia or hypoxia for 24 hours (each sample with 3 biological replicates).

first: Zhu

last: Chen

first: Zixuan

last: Wang

first: Chunchun

last: Zhu

first: Xiaoyun


title: Genomic and Biological Analysis of the Mechanism Underlying Dibifree Dietary Supplement

status: Public on Oct 17 2023

city: Taipei

first: Tzu-Yi

last: Huang

address: No. 155, Sec. 2, Linong St. Beitou Dist.

country: Taiwan

institute: National Yang Ming Chiao Tung University

summary: The mechanistic study employed NGS-RNAseq to capture differential gene expressions, which were subsequently analyzed using big data analysis, the GSEA predictions revealed that Dibifree reversed the pathological kidney gene pattern observed in patients with type 2 diabetes. The network diagram derived from comprehensive databases (KEGG, GO, and DO) depicted the correlations between Dibifree and diabetes, including diabetes-related comorbidities.

first: Tzu-yi

first: Ly

last: Doan


title: Multivalent binding of the tardigrade Dsup protein to heterologous chromatin promotes yeast survival and longevity upon exposure to oxidative damage

status: Public on Jan 14 2024

city: Durham

first: Michael-Christopher

last: Keogh

state: NC

address: 6 Davis Dr

institute: EpiCypher, Inc

summary: Tardigrades are remarkable in their ability to survive extreme environments. The damage suppressor (Dsup) protein is thought responsible for their extreme resistance to reactive oxygen species (ROS) generated by irradiation. Here we show that expression of Ramazzottius varieornatus Dsup in Saccharomyces cerevisiae reduces oxidative DNA damage and extends the lifespan of budding yeast with chronic oxidative damage. This protection from ROS requires either the Dsup HMGN-like domain or sequences C-terminal to same. Dsup associates with no apparent bias across the yeast genome, using multiple modes of nucleosome binding; the HMGN-like region interacts with both the H2A/H2B acidic patch and H3/H4 histone tails, while the C-terminal region binds DNA. These findings give precedent for engineering an organism by physically shielding its genome to promote survival and longevity in the face of oxidative damage.

overall_design: 12 CUT&RUN samples including three targets (IgG, H3K4me3, and FLAG) across yeast cells with four various Ramazzottius varieornatus Dsup plasmid integrations. Control target=IgG, Control condition=Empty Vector.

first: Rhiannon

last: Aguilar

first: Laiba

last: Khan

first: Nina

last: Arslanovic

first: Kaylah

last: Birmingham

first: Kritika

last: Kasliwal

first: Spike

last: Posnikoff

first: Ujani

last: Chakraborty

first: Allison

middle: R

last: Hickman

first: Rachel

last: Watson

first: Ryan

last: Ezell

first: Hannah

first: Martis

last: Cowles

first: Richard

last: Garner

first: Abraham

last: Shim

first: Ignacio

last: Gutierrez

first: Matthew

last: Marunde

first: Jessica

last: Tyler


title: Gene expression in glycerol-grown Yarrowia lipolytica Af4 (DHA producing strain) and Yarrowia lipolytica Po1h (non-producing stain) in different growth phases and different medium conditions

status: Public on Jan 01 2024

city: Saarbruecken

first: Michael

last: Kohlstedt

address: Campus A1.5

institute: Saarland University

summary:
mRNA was sampled during exponential growth phase (T1), beginning of stationary/production phase (T2), middle of production phase (T3-T4) and end of production phase (T5-T6)
strains: Y. lipolytica Af4 - DHA producer (Gemperlein et al., 2019) and Y. lipolytica Po1h - wild type

overall_design:
4 different setups: Af4 strain = C1 - condition 1 (C/N = 8.6, C/P = 41.3), C2 - condition 2 (C/N = 8.6, C/P = 95.2), C3 - condition 3 (C/N =17.2, C/P = 190.4), Po1h strain = C4 - condition 4 (C/N = 8.6, C/P = 95.2)
Condition 1 (producer strain): 20 g/L glycerol, 5 g/L (NH4)2SO4, 1.3 g/L PO4-;
Condition 2 (producer strain): 20 g/L glycerol, 5 g/L (NH4)2SO4, 0.65 g/L PO4-;
Condition 3 (producer strain): 40 g/L glycerol, 5 g/L (NH4)2SO4, 0.65 g/L PO4-;
Condition 4 (wild type): 20 g/L glycerol, 5 g/L (NH4)2SO4, 0.65 g/L PO4-

first: Sofija

last: Jovanovic

first: Christoph

last: Wittmann


title: Esophageal progenitor cell plasticity; a 3D organotypic model of epithelial regeneration

status: Public on Dec 14 2023

city: Cambridge

first: Irina

last: Mohorianu

address: Puddicombe Way

department: Wellcome-MRC Cambridge Stem Cell Institute

institute: University of Cambridge

summary: Epithelial stem cells are capable of remarkable plasticity, facilitating efficient regenerative responses following damage. Here, we present a versatile model of ectopic niche regeneration that provides evidence of a switch in epithelial stem cell identity as a response to foreign microenvironmental signals. A combination of 3D organotypic cultures, 3D confocal imaging and Next-Generation Sequencing reveal events of epithelial plasticity during the reepithelialization of denuded stroma. In this study we perform a temporal analysis that provides new insights on the mechanisms driving cell fate flexibility in adult epithelial stem cells.

overall_design: Single cell RNA sequencing of oesophageal epithelial cells cultured in a 3D organotypic system that recapitulates wound healing. Cells growing over their native stroma were compared to those growing over the foreign stroma of the dermis. The temporality of the process was captured by sequencing cells at day 3 and 10 into the regeneration process. For each of the four conditions, at least 3 biological replicates were performed.

first: Maria

last: Bejar

first: Paula

last: Jimenez-Gomez

first: Ilias

last: Moutsopoulos

last: Alcolea


title: RNA sequencing identifies human placentalIL3RAas a potential predictor of adverse cardiovascular outcomes in patients with severe preeclampsia

status: Public on Nov 09 2023

city: La Jolla

first: Mariko

last: Horii

address: 2880 Torrey Pines Scenic Dr

department: Pathology

institute: UCSD

summary: Background: Mortality from preeclampsia (PE) and PE-associated morbidities are 3-to 5-fold higher in persons of African ancestry than in those of Asian and European ancestries. The placenta is central to the etiology of PE. However, how and to what extent the placenta contributes to worse PE outcomes in persons of African ancestry is yet to be fully elucidated.  Objective: We aimed to identify molecular pathways that are unique or enriched in placentas of parturient persons of African ancestry with PE with severe features (sPE) compared to those of Asian and European ancestry with sPE. Study design: Bulk RNA sequencing was performed on 50 placentas from parturient persons with sPE of African (n=9), Asian (n=18) and European (n=23) ancestries and 73 normotensive controls of African (n=9), Asian (n=15) and European (n=49) ancestries. Results: Metabolism, hormone regulation and hypoxia/angiogenesis genes, previously described to be upregulated in PE, including: LEP, PAPPA2, INHA, FSTL3, FLT1, PHYHIP and ENG, were upregulated in sPE across ancestries, with high expression of FSTL3 being additionally associated with intrauterine growth restriction (p<.0001). Notably, LEP, FLT1 and PHYHIP were more highly upregulated in sPE placentas from parturient persons of African versus Asian ancestry. Genes associated with allograft rejection and adaptive immune response were selectively upregulated in placentas from African ancestry parturitions and not in those of Asian and European ancestries. Among the allograft rejection/adaptive immune response genes, IL3RA was of particular interest because the patient with the highest placental IL3RA level, a woman of African ancestry with IL3RA levels 4.5-fold above the average for African ancestry parturitions with sPE, developed postpartum cardiomyopathy, and was the only patient out of 123, that developed this condition. Interestingly, the sPE patients of Asian and European ancestries with the highest IL3RA levels for their ancestries developed unexplained tachycardia peripartum, necessitating echocardiography in the European ancestry patient. The association between elevated placental IL3RA levels and unexplained tachycardia or peripartum cardiomyopathy was found to be significant in the 50 sPE patients (p=.0005). Conclusions: African ancestry parturitions are associated with higher placental upregulation of metabolism (LEP) and hypoxia/angiogenesis (FLT1) genes, and selective upregulation of allograft rejection/adaptive immune response genes, including IL3RA. High placental expression of IL3RA may predict worse maternal cardiovascular outcomes, including peripartum cardiomyopathy. Studies evaluating placental IL3RA levels in peripartum cardiomyopathy cohorts are therefore warranted, as are broader studies evaluating placental factors in maternal cardiovascular outcomes postpartum.

overall_design:
Total RNA-seq of placental RNA from non-hypertensive control and severe preeclampsia from different ancestry

UPDATE: [Jan-10-2024] The Sample ancestry and sex characteristics were updated.

first: Omonigho

last: Aisagbonhi


title: Effect of chronic PM exposure on gene expression in the mouse lung tissue

status: Public on Dec 22 2023

city: Seoul

first: Myungkyung

last: Noh

address: Gwanak-ro 1

country: South Korea

institute: Seoul National University

summary: To identify differentially expressed genes in the lung by chronic PM exposure, we isolated mRNAs from the lung tissue from FVB/N mice after 4-weeks repeated intratracheal PM treatment

overall_design: Comparative gene expression profiling analysis of RNA-seq data for PM-treated lung tissues and its Veh (PBS) control counterparts.


title: Multi-omic profiling of the developing human cerebral cortex at the single cell level [snATAC-seq]

status: Public on Oct 12 2023

city: New York City

first: Jaroslav

last: Bendl

state: New York

address: One Gustave L. Levy Place, Department of Genetics and Genomics Sciences, Box 1210

department: Genetics and Genomics Sciences

institute: Icahn School of Medicine at Mount Sinai

summary: Human brain development starts during embryogenesis and extends postnatally to adulthood. During this time, the cellular complexity of the brain is established via dynamic changes in gene expression, mediated, in part, by the spatiotemporal activity of cis-regulatory elements. To better understand these processes, we performed simultaneous profiling of gene expression and chromatin accessibility in 45,549 individual nuclei, isolated from the human cortex across 6 broad developmental time-points from fetus to adult. We identified cell-type specific domains in which chromatin accessibility is highly correlated with gene expression. Differentiation pseudotime trajectories of gene expression in neuronal subpopulations indicate that chromatin accessibility at cis-regulatory elements precedes transcription and that dynamic changes in chromatin structure play a critical role in neuronal lineage commitment. In addition, using lineage-specific genes and peaks, we mapped cell-type specific genetic loci implicated in neuropsychiatric traits, including schizophrenia, major depressive disorder and bipolar disorder. Together, our results describe the complex regulation of cell composition at critical stages in lineage determination, serve as a developmental blueprint of the human brain and shed light on the impact of spatiotemporal alterations in gene expression on neuropsychiatric disease.

overall_design: snATAC-seq

first: Panos

last: Roussos

first: John

last: Fullard

first: Kaiyi

last: Zhu


title: Corticostriatal cocaine-seeking ensembles are defined by differing gene expression from sucrose-seeking ensembles using a within-subject dual self-administration and seeking mouse model

status: Public on Nov 08 2023

city: Fort Collins

first: Ana-Clara

last: Bobadilla

state: Colorado

address: 1350 Centre Ave

department: Biomedical Sciences

institute: Colorado State University

summary: Recurrent cocaine seeking is a hallmark of cocaine use disorder. To develop therapeutic targets, it is critical to understand the neurobiological changes specific to cocaine-seeking in context with the seeking of non-drug rewards, e.g., sucrose. The nucleus accumbens and medial prefrontal cortex are known regions associated with cocaine- and sucrose-seeking ensembles, i.e., a sparse population of co-activated neurons linked with behavior. Within ensembles, transcriptomic alterations in the NAc and mPFC underlie the learning and recall of cocaine- and sucrose-seeking behavior. However, the transcriptomics exclusively driving cocaine seeking independent from sucrose seeking have not yet been defined using a within-subject approach. Using Ai14:cFos-TRAP2 transgenic mice in a dual cocaine and sucrose self-administration model, we fluorescently sorted and characterized the transcriptomes defining cocaine-seeking in reference to the sucrose-seeking ensemble, overlapping ensemble in between cocaine and sucrose-seeking, and the non-ensemble population. Our data suggests there are robust transcriptomic changes linked with cocaine-seeking that differ from sucrose-seeking ensembles and the non-ensemble population which could guide future studies aimed to detangle cocaine-seeking behavior without altering non-drug reward seeking.

overall_design: The 48 RNA-sequencing fastq sample files are labeled in the sequential order: sex (male = M; female = F), region (nucleus accumbens = N; medial prefrontal cortex = P), replicate (replicate 1 = 1; replicate 2 = 2; replicate 3 = 3), and cell population type (cocaine-seeking ensemble = C; sucrose-seeking ensemble = S; overlapping ensemble = O; non-ensemble = NonEns). Supplemental files for each sample are unnormalized and unfiltered transcript count output from Salmon.

first: Litif

middle: G

last: Carl

first: Flom

last: Levi

first: Sandum

last: Kathryn

first: Hodgins

last: Skylar

first: Vaccaro

last: Lucio

first: Stitzel

last: Jerry

first: Ungerleider

last: Nathan

first: Mannino

last: Maria Constanza

first: Gigley

last: Jason

first: Schoborg

last: Todd

first: Bobadilla

last: Ana-Clara


title: The changes of miRNAs in plasma small extracellular vesicles (sEV) isolated from 8-week diabetic rats compared with control animals

status: Public on Sep 24 2023

city: Xi'an

first: Feng

last: Fu

state: Shaanxi

address: Changle Xi Road 169

institute: Fourth Military Medical University

summary: Compared with plasma sEV (Con-sEV) from control rats, plasma sEV (DM-sEV) from 8-week diabetic rats significantly induced cardiomyocyte apoptosis as evidenced by increased percentage of apoptotic cells and activity of pro-apoptotic protein caspase 3. The proapoptotic effect of DM-sEV was blunted by RNase but not proteinase K, suggesting that DM-sEV exerted the cardiotoxic effects mainly through their contained RNAs. Increasing evidence suggests that miRNAs are the most important molecules by which sEV regulate recipient cell function. To identify  the sEV-containing specific miRNAs responsible for the effects, Con-sEV and DM-sEV were subjected to miRNA sequencing.

overall_design: To explore the changes of miRNAs in plasma DM-sEV compared with Con-sEV, Con-sEV and DM-sEV were isolated from the plasma of control and 8-week diabetic rats. Total RNAs were extracted from sEV purified from 2 ml of rat plasma. The PCR products derived from the 18- to 30- nucleotide RNA molecules were purified by electrophoresis and sequenced using the Illumina HiSeq 2500 platform. Differential expression analysis of two groups was performed using the DEGseq R package.

first: Mingge

last: Ding

first: Yanyan

last: Du


title: Mechanisms of insertions at a double strand break

status: Public on Jul 03 2023

first: Jaewon

last: Min

address: 1130 St. Nicholas Ave

department: Pathology and Cell Biology (in the Institute for Cancer Genetics)

institute: Columbia University

summary: Insertions and deletions (indels) are common sources of structural variation, and insertions originating from spontaneous DNA lesions are frequent in cancer. We developed a highly sensitive assay (Indel-Seq) to monitor rearrangements in human cells at the TRIM37 acceptor locus that reports indels stemming from experimentallyinduced and spontaneous genome instability. Templated insertions, which derive from sequences genome-wide, require contact between donor and acceptor loci, homologous recombination, and are stimulated by DNA end-processing. Insertions are facilitated by transcription and involve a DNA/RNA hybrid intermediate. Indel-Seq reveals that insertions are generated via multiple pathways. The broken acceptor site anneals with a resected DNA break or invades the displaced strand of a transcription bubble or R-loop followed by DNA synthesis, displacement and then ligation by nonhomologous end-joining. Our studies identify transcription-coupled insertions as a critical source of spontaneous genome instability that are distinct from cut-and-paste events

overall_design: Indel-seq, Hi-C

first: Junfei

last: Zhao

first: Jennifer

last: Zagelbaum

first: Allana

last: Schooley

first: Jean

last: Gautier


title: Developing a novel human adult kidney organoid model to recapitulate injury-associated regeneration and polycystic kidney disease [RNA-Seq]

status: Public on Aug 28 2023

city: Jinan

first: liqiang

last: guo

address: No. 107, Wenhua West Road

department: Shandong University

institute: Qilu Hospital

summary: Current renal organoid models derived from embryonic or induced pluripotent stem cells mimic development. Yet, few studies have attempted to generate organoids from human adult kidney to recapitulate regeneration or pathological dysregulation in vitro. Here, we report a novel expanding regenerative organoids culture system from renal cortex and medulla. Transcriptomic sequencing and immunostaining identified that these organoids share similar molecular features with kidney injury-responsive regeneration. Heterogeneous populations in organoids including cycling epithelial progenitors and differentiated cell types were identified by single cell sequencing including proximal tubules, principal cells and collecting duct (CD) progenitors that can be induced into functional CD system. Furthermore, we established polycystic organoids derived from patients that represent an advanced platform for polycystic kidney disease (PKD) modeling. By drug screening, QNZ, GSK2193874 and AMPK activators were shown to significantly reduce polycystic growth. Our results demonstrated a novel in vitro renal organoid model to study regenerating adult renal cells and PKD mechanism, providing tools for discovery of therapeutic targets.

overall_design: Comparative gene expression profiling analysis of RNA-seq data for kidney organoids.

first: Liqiang

last: Guo

first: Yujia

last: Fan

first: Haoran

first: Xinyan

last: Zhang

first: Shan

last: Jiang

first: Yong

last: Guan

first: Lingtong

last: Ren

first: Yachun

last: An

first: Xiaohui

first: Huixian

last: Sun

last: Kong

first: Benkang

last: Shi

first: Fan

last: Yi

first: Huili

last: Hu

first: Shengtian


title: Antibody-mediated Inhibition of Global HLA/LILR Interactions Breaks Innate ImmuneSystemTolerance and Unleashes Potent Anti-Tumor Immunity

status: Public on Mar 27 2024

city: Bethesda

first: Ethan

middle: M

last: Shevach

address: 10 Center Drive, Building 10, Room 11N315

institute: NIAID/NIH

summary: We have conducted a study to investigate how blocking HLA/LILR affects the activation of immune cells in the tumor microenvironment. We perfused a freshly isolated primary colon cancer biopsy sample with hIgG1 LALAPG or DX17 LALAPG for 48 hours. We then isolated CD45+ leukocytes from the tumor sample using magnetic cell sorting. Subsequently, we processed the resulting tumor-infiltrating lymphocytes (TILs) for single-cell RNA-seq and Cite-seq analysis. We compared the transcriptomes of NK cells, monocytes, and memory T cells under the two different culture conditions

overall_design: We utilized an oxygenated ex vivo perfusion circuit (Patent No. PCT/US2021/021525) to maintain tumors that were removed from patients in near-physiological conditions. We perfused the tumor samples with autologous patient plasma and hIgG1 LALAPG and DX17-LALAPG (5ug/ml) for 48 hours. After the perfusion was complete, we isolated tumor-infiltrated lymphocytes (TILs) by dissociating the tumor explants into a single-cell suspension. We then analyzed the TILs, including NK cells, monocytes, and T cells, in tumor microenvironments using sc-RNA-seq and CITE-seq.

first: Abir

last: Panda

first: Kannan

last: Natarajan

first: Martha

last: Teke

first: Jonathan

last: Hernandez

first: David

last: Margulies

first: Bryan

last: Fisk

first: Brittany

last: Dulek

first: Neelam

last: Redekar


title: RNA-seq for Col-0, atchz1ab, hta9-1hta11-2, atchz1ab hta9-1hta11-2, arp6-1, atchz1ab arp6-1

status: Public on Apr 01 2023

city: Shanghai

first: Jiachen

last: Wang

state: Shanghai

address: No. 2005, Songhu Road

department: Institute of Plant Biology

institute: Fudan University

summary:
To investigate the effect of the interaction between the AtChz1A/B, H2A.Z and ARP6, we analysed differentially expressed genes compared to the mutant and wild-type by RNA-seq.
We then performed gene expression profiling analysis using data obtained from RNA-seq of 6 different plants including mutants and wild-type.

overall_design: Comparative gene expression profiling analysis of RNA-seq data for Col-0, atchz1ab, hta9-1hta11-2, atchz1ab hta9-1hta11-2, arp6-1, atchz1ab arp6-1.

first: Aiwu

last: Dong

first: Wen-Hui

last: Shen

first: Jiabing

last: Wu

first: Liufan

last: Yin


title: Effect of mild respiratory SARS-CoV-2 infection on brainstem endothelial transcriptome

status: Public on Aug 25 2023

city: Chicago

first: Sarah

middle: Elizabeth

last: Lutz

state: IL

address: 808 S. Wood St., Rm 578 MC 512, Anatomy Cell Biology Lutz Lab, Anatomy Cell Biology Lutz Lab

department: Anatomy and Cell Biology

institute: University of Illinois at Chicago

summary: To investigate the transcriptional response of brainstem endothelial cells to mild respiratory infection, 12-month-old male C57Bl/6 mice were intranasally inoculated with SARS-CoV-2 MA10 strain or with saline.

overall_design:
Brainstem were digested with papain, microvessels were isolated by differential centrifugation through a BSA gradient, microvessel fragments were digested to single cells with Collagenase, myelin was depleted, and CD31-positive selection beads were used three sequential times to isolate brainstem endothelial cells. Bulk RNA was used for sequencing.
Comparative gene expression profiling analysis of bulk RNA-seq data for brainstem endothelial cells from 12-month-old and 2-month-old male C57Bl/6J mice at 4 days after inoculation with SARS-CoV-2 MA10 or vehicle.

first: Troy

middle: N

last: Trevino

first: Seshadri

last: Niladhuri

first: Avital

last: Fogel

first: Jacob

last: Class

first: Mark

last: Sanborn

first: Felecia

last: Marattoli

first: Leon

last: Tai

first: Benoit

last: Vanhollebeke

first: Jalees

last: Rehman

first: Justin

last: Richner


title: Comprehensive Analysis of ceRNA Network Composed of circRNA, miRNA, and mRNA in septic acute kidney injury patients based on RNA-seq

status: Public on Sep 14 2023

city: Yinchuan

first: Wen-jie

last: Zhou

address: No. 804, Shengli South Street, Xingqing District, Yinchuan City, Ningxia

institute: General Hospital of Ningxia Medical University

summary: Sepsis is a complex, life-threatening clinical syndrome that can cause other related diseases, such as acute kidney injury (AKI). Circular RNA (circRNA) is a type of non-coding RNA with a diverse range of functions, and it plays essential roles in miRNA sponge. CircRNA plays a huge part in the development of various diseases. CircRNA and the competing endogenous RNA (ceRNA) regulatory network are unknown factors in the onset and progression of septic AKI (SAKI). This study aimed to clarify the complex circRNA-associated regulatory mechanism of circRNAs in SAKI.

overall_design: We collected 10 samples of whole blood of adults, including 5 cases of SAKI and 5 cases of healthy controls. Moreover, five cases were each analyzed by RNA sequencing, and we identified differentially expressed circRNA, miRNA, and mRNA (DEcircRNAs, DEmiRNAs, and DEmRNAs, respectively). All samples were from SAKI patients with intraperitoneal infection.

first: Si-Rong

last: Ma

first: Qi

first: Ya-Nan

first: Wen-Jie


title: Determination of MHV RNA poly(A) tail length and 3' end additions in infected 17-CL1 and NCTC cells

status: Public on Mar 23 2023

city: DURHAM

first: ANKIT

last: GUPTA

address: TW 111 ALEXANDER DRIVE

department: RDBL

institute: NIEHS

summary: This SuperSeries is composed of the SubSeries listed below.

sample_organism:
Mus musculus
Murine hepatitis virus

platform_organism:
Mus musculus
Murine hepatitis virus

overall_design: Refer to individual Series


title: Targeting the fibroblast growth factor pathway in molecular subtypes of castration-resistant prostate cancer

status: Public on Sep 19 2023

city: Seattle

first: Ilsa

last: Coleman

state: WA

address: 1100 Fairview Ave N, E2-112

department: Human Biology

institute: Fred Hutchinson Cancer Center

summary: Androgen receptor (AR) pathway inhibition remains the cornerstone for first- and second-line prostate cancer therapies. Although AR signaling inhibitors, such as enzalutamide and abiraterone extend survival in recurrent and castration-resistant prostate cancer (CRPC), durable and complete responses are rare. Resistance mechanisms employed by metastatic CRPC include amplification of AR and AR splice variants in AR-positive CRPC (ARPC) and conversion to AR-null phenotypes, such as double-negative prostate cancer (DNPC) and small cell or neuroendocrine prostate cancer (SCNPC). We have shown previously that DNPC can bypass AR-dependence through fibroblast growth factor (FGF) signaling. However, the role of the fibroblast growth factor receptor (FGFR) pathway in other molecular subtypes of CRPC has not been elucidated.

overall_design: RNA sequencing of prostate tumor patient-derived xenograft (PDX) models, prostate tumor cell lines, and CRPC metastases using Illumina TruSeq Library prep and sequenced on Illumina HiSeq 2500 and NovaSeq 6000.

last: Labrecque

first: Lisha

last: Brown

first: Holly

last: Nguyen

first: Susan

last: Dalrymple

first: W

last: Brennen

first: John

last: Isaacs

first: Dapei

last: Li

first: Bryce

last: Lakely

first: Diana

last: DeLucia

middle: K

last: Lee

first: Michael

last: Schweizer

first: Daniel

middle: W

last: Lin

first: Eva

last: Corey

first: Peter

middle: S

last: Nelson

first: Colm

last: Morrissey


title: Lymphoid Follicle Spatial Transcriptomics Resolve an Emphysema-Specific B Cell Signature in COPD

status: Public on Nov 21 2023

city: Houston

first: Scott

middle: Andrew

last: Ochsner

state: TX

address: One Baylor Plaza

department: Molecular and Cellular Biology

institute: Baylor College of Medicine

summary: Using Geomx's Digital Space Profiling method for WTA RNA transcriptomics in lung tertiary lymphoid structures (TLS, follicles), we assessed paraffin-embedded and OCT-embedded lung sections from 48 patients, which were classified as Never Smoker Controls (NSC, n=8), Smoker Controls (SC, n=13), and COPD GOLD1-4 patients (n=27 patients).  we identified 19 patients with tertiary lymphoid structures (TLS), distributed as 13 COPD patients and 6 SC subjects, with 115 TLS data used for the final data analysis.

overall_design: After consenting, lung samples were collected from Smoker Controls (defined pack years >10), and COPD GOLD1-4 patients (defined according to spirometry results). Samples: Pathologist assessed lung samples were obtained from patients undergoing lung biopsy for non-cancer causes or because they needed to receive a lung transplant (COPD stage 4 patients). Lungs were either fresh fixed in OCT fixative and kept at -80C, or, they were fixed in formalin for 24 hours and subsequently embedded in paraffin. ROIs were collected from CD45 labeled lyphoid follices from COPD patients and from smoker control patients.

first: Joselyn

middle: J

last: Rojas-Quintero

middle: A

first: Francesca

last: Polverino


first: Wen-jie

last: Zhou

first: Si-Rong

last: Ma

first: Qi

first: Ya-Nan

first: Wen-Jie


title: Effect of vaccination, marketing strategy, and bovine respiratory disease development on at arrival transcriptomes of recently weaned beef cattle

status: Public on Mar 09 2023

city: Canyon

first: Matthew

middle: Adam

last: Scott

address: 3201 Russell Long Blvd

department: Large Animal Clinical Sciences

institute: Texas A&M University

summary: Jugular whole blood samples (Tempus Blood RNA tubes) were collected and utilized from 43 cattle, specifically from all cattle diagnosed with bovine respiratory disease (BRD) during Texas backgrounding (n=32) and randomly selected cattle never treated for BRD (n=11). Total RNA was isolated from blood samples, and were library prepared and sequenced via Illumina NovaSeq 6000 S4 chemistry. Samples were bioinformatically processed in a HISAT2/StringTie2 pipeline, and stratified based on BRD diagnosis and marketing strategy (Auction versus Direct marketing and transport). Differential expression analysis was conducted in R, utilizing an additive, multifactor generalized linear model and blocking for Mississippi pasture and vaccination status. Genes were considered differentially expressed with an FDR cutoff of 0.05. The objective of this study was to identify differentially expressed genes and mechanisms within and across marketing cohorts with and without BRD.

overall_design: Fourty-three whole blood RNA samples selecting for mRNA sequencing (TruSeq Stranded mRNA) taken upon arrival to a Texas backgrounding facility.


title: Single-cell and bulk RNA sequencing of mouse atherosclerosis disease stage course

status: Public on Mar 17 2023

city: Kuopio

first: Tiit

last: Örd

address: Neulaniementie 2

country: Finland

institute: A.I. Virtanen Institute for Molecular Sciences, University of Eastern Finland


title: Alteration of Microglial Metabolism and Inflammatory Profile Contributes to Neurotoxicity in Frontotemporal Dementia 3

status: Public on Aug 10 2023

city: Copenhagen

first: Christian

last: Anthon

address: Thorvaldsensvej 57

country: Denmark

institute: University of Copenhagen

summary: Transcriptome profiling of microglia cells carrying a G>C mutation at the last exon (exon six) of the CHMP2B gene linked to frontotemporal dementia (dbSNP: rs63750652) and of the corresponding isogenic controls. Heterozygous and homozygous mutant cells were obtained by precision CRISPR/Cas9 genome editing. All cells were derived from human induced pluripotent stem cells (healthy donor cell line).

overall_design: Comparison between hiPSC-derived microglia carrying a G>C splice acceptor CHMP2B mutation linked to frontotemporal dementia, knocked-in via CRISPR/Cas9, and isogenic controls.

first: Henriette

last: Haukedal

first: Signe

last: Lorenzen

first: Emil

last: Westi

first: Giulia

middle: I

last: Corsi

first: Veerendra

middle: P

last: Gadekar

first: Amanda

last: McQuade

first: Hayk

last: Davtyan

first: Nadezhda

middle: T

last: Doncheva

first: Benjamin

last: Schmidt

first: Abynaya

last: Chandrasekaran

first: Stefan

last: Seemann

first: Susanna

last: Cirera

first: Mathew

last: Blurton-Jones

first: Morten

last: Meyer

first: Jan

last: Gorodkin

first: Blanca

last: Aldana

first: Kristine

last: Freude


title: DNA methylation in Syrian hamster female fetal cells (gestation day 13.5) exposed in vitro to 5-aza-2’deoxycytidine (5aCdR)

status: Public on Feb 10 2023

city: Ottawa

first: Matthew

last: Meier

state: Ontario

address: 251 Sir Frederick Banting Driveway

department: Health Canada

country: Canada

institute: Government of Canada

type: Methylation profiling by high throughput sequencing

summary: Purpose: To validate the reduced representation bisulfite sequencing (RRBS) methodology by comparing DNA methylation pattern in Syrian hamster fetal (SHF) primary cells to a SHF cell line (MT2) exposed to the DNA methyl transferase inhibitor,5aCdR. The MT2 cell line was originally derived from the expansion of a benzo[a]pyrene-induced morphologically transformed clone (Pickles et al 2016. Mutat.Res.Genet.Toxicol.Environ Mutagen. 802:50-58).

overall_design: The DNA methylation profiles of untreated SHF cells (4 biological replicates) were compared to untreated MT2 cells (4 culture wells as technical replicates, 0.05% DMSO as vehicle) and three wells treated with 5aCdR (5uM, 48 h).   All cells were confirmed female using a rapid XY qPCR assay.

first: Daniel

last: Desaulniers

first: Cathy

last: Cummings-Lorbetskie

first: Remi

last: Gagne


title: Histopathologic and transcriptome profiling identify novel trophoblast lineage-specific defects in preeclampsia

status: Public on Jan 10 2023

city: La Jolla

first: Mariko

last: Horii

address: 2880 Torrey Pines Scenic Dr

institute: UCSD

summary: Preeclampsia (PE) is a heterogeneous disease which lacks pathophysiology-based subclassification. Current clinical classification is based on gestational age at diagnosis and severity of disease. However, PE placentas have heterogeneous findings on pathologic exam. We combined clinical, pathological, immunohistochemical (IHC), and transcriptomic profiling to better subclassify this disease. 303 PE and 1388 non-hypertensive controls were included, with subgroups of samples used for each analysis. Detailed clinical and placental pathologic data were abstracted from our Obstetric Registry. Tissue studio (Definiens) was used for IHC analysis. RNAseq was performed using Illumina-NovaSeq using our standard pipeline. We found that maternal vascular malperfusion (MVM) in the placenta is associated with preterm PE and small-for-gestation neonates, with further subclassification into groups with and without fetal vascular malperfusion (FVM). Interestingly, MVM with FVM was further characterized by loss of proliferative cytotrophoblast, as confirmed by p63 IHC. Finally, transcriptomic analysis identified pathways associated with hypoxia and reduced cell-proliferation in PE-MVM placentas, and further subclassified this group into syncytiotrophoblast (STB)hi and extravillous trophoblast (EVT)hi PE, confirmed by IHC for trophoblast lineage-specific markers. Our findings suggest that PE can be subclassified based on underlying pathophysiologic changes, allowing identification of pathways which can be targeted for diagnostic and therapeutic purposes.

overall_design: Total RNA-seq of placental RNA from non-hypertensive control and severe preeclampsia.

first: Mana

last: Parast

first: Louise

middle: C

last: Laurent

first: Cuong

last: To

first: Robert

middle: E

last: Morey


title: Gene expression profile at single cell level of lymphocytes cells for Pan-T cell analysis

status: Public on Jan 14 2023

first: Linghua

last: Wang

address: 1881 East Road,

institute: MD Anderson Cancer Center

summary: Tumour infiltrating T lymphocytes (TILs) have provided an attractive avenue for cancer treatment. Yet, the various states of TILs in tumour immune microenvironment (TIME) have not been fully characterized. Here, we present a single-cell atlas of T cells, encompassing 308,048 transcriptomes, spanning 16 different cancer types and 9 types of healthy/cancer-adjacent tissues. This allowed elucidation of 32 transcriptionally distinct T cell subsets, including cell states not reliably observable in individual datasets and those overlooked by previous studies. Our analysis revealed heterogenous subpopulations of follicular helper, regulatory, and proliferative T cells and a high degree of intertumoural heterogeneity in cell states and compositions, providing rich biological insights into the spectrum of TIL phenotypes. We identified a stress response state (TSTR) characterized by unique expression of heat-shock genes. Notably, by applying multiple spatial profiling approaches, we demonstrate TSTR cells are detectable in situ in the TIME across different cancer types, primarily in lymphocyte aggregates that are within tumor beds or surrounding tumor edges. We correlated TIL states and phenotypes with genomic, pathological, and clinical features in large cohorts of treatment-naïve patients as well as in patients treated with immune checkpoint blockade (ICB). We observed significant enrichment of intratumoural CD4/CD8 TSTR cells following ICB therapy, particularly, in non-responsive tumors, suggesting their potential role in immunotherapy resistance. Lastly, this study provides a T cell reference map via a dedicated web portal and an automatic alignment and annotation tool as a resource, supporting T cell therapy optimization and biomarker discovery.

overall_design:
scRNA-seq profiling was performed on lungs from Gprc5a-/- mice treated with nicotine-derived nitrosamine ketone (NNK) or saline at the end of exposure (EOE, timepoint at which lungs are still clear of lesions) and at 7 months post-exposure, the time point of KM-LUAD onset in all mice (n = 4 mice per group and time point). Spatial transcriptomes of lung tissues from mice at 7 months post-exposure to NNK (n = 3) were performed to further characterize and validate our findings of the extences of KACs in mouse models.
**RAW data not provided due to protection under IRB protocol**

first: Michael

last: Green

first: Qing

last: Deng

first: Xiuning

last: Le

first: Jiang-Jiang

last: Qin

first: Xiang-Dong

last: Cheng

first: Amir

last: Jazaeri

first: Yanshuo

last: Chu


title: Single-cell transcriptomic analysis reveals the developmental trajectory and transcriptional regulatory networks of pigment glands in Gossypium bickii [scRNA-seq]

status: Public on Apr 21 2023

city: Hangzhou

first: Yue

last: SUN

state: Zhejiang

address: Yuhangtang Rd

institute: Zhejiang University

summary: Comprehensive utilization of cottonseeds is limited by the presence of pigment gland and its inclusion gossypol. The ideal cotton is glandless-seeds and glanded-plant, a trait found in only few Australian wild cotton species, including Gossypium bickii. Introgressing the trait to cultivated species is proved to be difficult. Understanding the biological processes towards pigment gland morphogenesis and the associated underlying molecular mechanisms will facilitate breeding cultivated cotton varieties with the trait of glandless-seeds and glanded-plant. Single-cell RNA sequencing (scRNA-seq) was performed on 12,222 protoplasts isolated from cotyledons of germinating G. bickii seeds 48-hours after imbibition. Clustered into 14 distinct clusters unsupervisedly, these cells could be grouped into eight cell populations with the assistance of known cell marker genes. The pigment gland cells were well separated from others, and could be separated into pigment gland parenchyma cells, secretory cells, and apoptotic cells. In this study, integrating pigment gland cells developmental trajectory, transcription factors regulatory networks, and core transcription factors functional validation, a relatively complete model was proposed for pigment gland formation. Light and gibberellin were verified to promote the formation of pigment glands. Besides, three novel genes, GbiERF114 (ETHYLENE RESPONSE FACTOR 114), GbiZAT11 (ZINC FINGER OF ARABIDOPSIS THALIANA 11) and GbiNTL9 (NAC TRANSCRIPTION FACTOR-LIKE 9), were found to affect pigment gland formation. These findings shed new insights into pigment gland morphogenesis and lay the cornerstone for future cotton scRNA-seq investigations.

overall_design: one sample from cotyledons of germinating G. bickii seeds 48-hours after imbibition

last: Sun

first: Yifei

last: Han

first: Kuang

last: Sheng

first: Shuijin

last: Zhu

first: Tianlun

last: Zhao


title: Chronology of DNA methylation changes through transformation stage leading to senescence by-pass in Syrian hamster fetal primary cells exposed to benzo[a]pyrene

first: Matthew

last: Meier

summary: Purpose: To use reduced representaion bisulfite sequencing to measure differential genome methylation among: 1. cells treated with benzo[a]pyrene (B[a]P) versus vehicle alone (DMSO) using the Syrian Hamster Cell Transformation Assay method; 2. cells originating from normal (Nc) versus morphologically transformed (MTc) colonies; 3. cells in senescence (SEN) versus those that have bypassed senescence (SENbp).

overall_design: Reduced representation bisulfite sequencing was performed to measure cytosine methylation within genomic DNA. Four biological replicates were sampled to study B[a]P versus untreated colonies (DMSO) and MT versus N colonies. Four technical replicates were sampled to study senescence versus senescence-bypass. All cells were confirmed male using a rapid XY qPCR assay.

first: Daniel

last: Desaulniers

first: Remi

last: Gagne

first: Cathy

last: Cummings-Lorbetskie


title: Stalled ribosomes are signals for metabolic regulation by the ribotoxic stress response

status: Public on Nov 16 2022

city: Lausanne

first: David

last: Gatfield

address: Genopode building

institute: University of Lausanne

summary: Impairment of translation can lead to stalling and collision of ribosomes which constitute an activation platform for several ribosomal stress-surveillance pathways. Among these is the Ribotoxic Stress Response (RSR), where ribosomal sensing by the MAP3K ZAKa leads to activation of p38 and JNK kinases. Despite these insights, the physiological ramifications of ribosomal impairment and downstream RSR signaling remain elusive. Here we show that stalling of ribosomes is sufficient to activate ZAKa. In response to amino acid deprivation and full nutrient starvation, RSR impacts on the ensuing metabolic responses in cells, nematodes and mice. The RSR-regulated responses in these model systems include regulation of AMPK and mTOR signaling, survival under starvation conditions, stress hormone production and regulation of blood sugar control. In addition, ZAK-/- mice present with a lean phenotype. Our work highlights stalled ribosomes as metabolic signals and demonstrates a role for RSR signaling in metabolic regulation.

overall_design: Comparative ribosome footprint of RIBO-seq data of mouse livers tissues grown in standard diet and leucine deficient diet

first: Goda

last: Snieckute

first: Aitana

middle: V

last: Genzor

first: Anna

last: Vind

first: Laura

middle: R

last: Tønnesen

first: Mark

last: Stoneley

first: Sébastien

last: Chamois

first: René

last: Dreos

first: Cathrine

last: Nordgaard

first: Frederike

last: Sass

first: Melanie

last: Blasius

first: Aida

last: Rodriguez-Lopez

first: Solveig

middle: H

last: Brynjulfsdottir

first: Kasper

middle: L

last: Andersen

first: Anne

last: Willis

first: Lisa

middle: B

last: Frankel

first: Steen

last: Poulsen

first: Zach

last: Gerhart-Hines

first: Christoffer

last: Clemmensen

first: Simon

last: Bekker-Jensen


title: scMultiome analysis identifies embryonic hindbrain progenitors with mixed rhombomere identities

status: Public on Aug 08 2023

city: Aurora

first: Charles

last: Sagerstrom

state: CO

address: 12801 East 17th Avenue

department: Pediatrics

institute: University of Colorado Medical School

summary: Rhombomeres serve to position neural progenitors in the embryonic hindbrain, thereby ensuring appropriate neural circuit formation, but the molecular identities of individual rhombomeres and the mechanism whereby they form have not been fully established. Here we apply scMultiome analysis in zebrafish to molecularly resolve all rhombomeres for the first time. We find that rhombomeres become molecularly distinct between 10hpf (end of gastrulation) and 13hpf (early segmentation). While the mature hindbrain consists of alternating odd- versus even-type rhombomeres, our scMultiome analyses do not detect extensive odd versus even characteristics in the early hindbrain. Instead, we find that each rhombomere displays a unique gene expression and chromatin profile. Prior to the appearance of distinct rhombomeres, we detect three hindbrain progenitor clusters (PHPDs) that correlate with the earliest visually observed segments in the hindbrain primordium and that represent prospective rhombomere r2/r3 (possibly including r1), r4 and r5/r6, respectively. We further find that the PHPDs form in response to Fgf and RA morphogens and that individual PHPD cells co-express markers of multiple mature rhombomeres. We propose that the PHPDs contain mixed-identity progenitors and that their subdivision into individual mature rhombomeres requires resolution of these mixed-identity cell states.

overall_design: Untreated zebrafish embryos at 10hpf (whole embryos), 13hpf (dissected hindbrain regions) and 16hpf (dissected hindbrain regions), as well as DEAB-treated 13hpf embryos (dissected hindbrain regions) were assayed by combined scRNAseq/scATACseq.

first: Yong-Il

last: Kim

first: Rebecca

last: O’Rourke

middle: G

last: Sagerström


title: Lactate-dependent Transcriptional Regulation Controls Mammalian Eye Morphogenesis

status: Public on Jun 07 2023

first: NOZOMU

last: TAKATA

state: Illinois

address: 303 East Superior Street, 10-220

department: Center for Vascular and Developmental Biology

institute: Northwestern University Feinberg School of Medicine


title: Epigenetic reprogramming of intestinal stemness by dietary arachidonic acid

status: Public on Mar 01 2023

city: Cold Spring Harbor

first: Aybuke

last: Alici

state: NY

address: 1 Bungtown Rd.

institute: Cold Spring Harbor Laboratory


title: Therapeutic Implications for Intrinsic Phenotype Classification of Metastatic Castration Resistant Prostate Cancer

status: Public on May 03 2022

first: Ilsa

last: Coleman

summary: Metastatic prostate cancers are recognized to exhibit subtypes categorized by underlying genomic alterations and phenotypes largely partitioned by androgen receptor signaling and neuroendocrine activity. In the present study we evaluated a phenotypic classification approach originally developed for subtyping breast carcinomas using the PAM50 gene signature. PAM50 subtypes associated with specific genotypes such as RB1 loss and phenotypes such as small cell/neuroendocrine carcinoma as well as tumor histology including cribriform morphology. In the context of clinical translation, PAM50 classification segregated tumors into groups with distinct druggable targets such as cell surface proteins amenable to antibody-drug-conjugates (ADCs). Classification into Luminal A, Luminal B and Basal tumors associated with time on androgen receptor signaling inhibitors, and responses to taxane chemotherapy. These findings support further clinical investigation of PAM50-based classification for prostate cancer patient stratification in therapeutic studies.

overall_design: RNA sequencing of prostate tumor patient-derived xenograft (PDX) models using Illumina TruSeq Library prep and sequenced on Illumina NovaSeq 6000 or HiSeq 2500.

middle: M

first: Navonil

last: De Sarkar

first: Colm

last: Morrissey

first: Li

last: Xin

first: Martine

last: Roudier

first: Erolcan

last: Sayar

first: Dapei

last: Li

first: Eva

last: Corey

first: Michael

last: Haffner

first: Peter

last: Nelson


title: SmcHD1 underlies the formation of H3K9me3 blocks on the inactive X chromosome in mice [ChIP-seq]

status: Public on Jul 20 2022

city: Toyonaka

first: Koji

last: Nagao

state: Osaka

address: 1-1 Machikaneyama

department: Graduate School of Science

institute: Osaka University

summary: Stable silencing of the inactive X chromosome (Xi) in female mammals is crucial for the development of embryos and their postnatal health. SmcHD1 is essential for stable silencing of the Xi, and its functional deficiency results in derepression of many X-inactivated genes. Although SmcHD1 has been suggested to play an important role in the formation of higher-order chromatin structure of the Xi, the underlying mechanism is largely unknown. Here, we explore the epigenetic state of the Xi in SmcHD1-deficient epiblast stem cells and mouse embryonic fibroblasts in comparison with their wild-type counterparts. The results suggest that SmcHD1 underlies the formation of H3K9me3-enriched blocks on the Xi, which, although the importance of H3K9me3 has been largely overlooked in mice, play a crucial role in the establishment of the stably silenced state. We propose that the H3K9me3 blocks formed on the Xi facilitate robust heterochromatin formation in combination with H3K27me3, and that the substantial loss of H3K9me3 caused by SmcHD1 deficiency leads to aberrant distribution of H3K27me3 on the Xi and derepression of X-inactivated genes.

overall_design: Allele-specific ChIP-seq analysis of epiblast stem cells (EpiSCs) and mouse embryonic fibroblasts (MEF) prepared from female fetuses deficient for SmcHD1

first: Saya

last: Ichihara

first: Takehisa

last: Sakaguchi

first: Chikashi

last: Obuse

first: Takashi

last: Sado