title: To find the differentially regulated genes between WT and E81Q, WT and Q62L group [RNA-seq]

city: guangzhou

first: qiannan

last: ren

address: 651 DF ROAD

institute: SYSUCC

summary: The androgen receptor (AR) plays an important role in male-dominant hepatocellular carcinoma, and specific acquired somatic mutations of AR have been observed in HCC patients. Our previous research have established the role of AR wild type as one of the key oncogenes in hepatocarcinogenesis. However, the role of hepatic acquired somatic mutations of AR remains unknown. In this study, we identify two crucial acquired somatic mutations, Q62L and E81Q, contributing to tumorigenesis. By RNA-sequencing, we found the differential genes in the mutant group compared with the WT group.

overall_design: We constructed an animal model of hydrodynamic transgenic mice containing AR mutations gene. The mice liver tumor tissue was subjected to CHIP-seq and RNA-seq,separately

first: REN

last: QIANNAN


title: To find the differentially regulated genes between WT and E81Q, WT and Q62L group [ChIP-seq]

status: Public on Jan 10 2024

country: China

type: Genome binding/occupancy profiling by high throughput sequencing

overall_design: We constructed an animal model of hydrodynamic transgenic mice in which tumor-forming tumor tissue was subjected to CHIP-seq and RNA-seq


title: The miR-183/96/182 cluster is a checkpoint for resident immune cells and shapes the cellular landscape of the cornea.

city: Detroit

first: Shunbin

last: Xu

state: MI

address: 540 E Canfield St, Scott Hall 8133/8137

department: Opthalmology, Visual and Anatomical Sciences

country: USA

institute: Wayne State University, School of Medicine

type: Expression profiling by high throughput sequencing

summary: The conserved miR-183/96/182 cluster (miR-183C) regulates both corneal sensory innervation and corneal resident immune cells (CRICs). This study is to uncover its role in CRICs and in shaping the corneal cellular landscape at a single-cell (sc) level.

overall_design: Corneas of naïve, young adult [2 and 6 months old (mo)], female miR-183C knockout (KO) mice and wild-type (WT) littermates were harvested and dissociated into single cells. Dead cells were removed using a Dead Cell Removal kit. CD45 + CRICs were enriched by Magnetic Activated Cell Sorting (MACS). scRNA libraries were constructed and sequenced followed by comprehensive bioinformatic analyses

first: Weifeng

last: Li

first: Katherine

last: Gurdziel

first: Ahalya

last: Pitchaikannu

first: Naman

last: Gupta

first: Linda

last: Hazeltt


title: EZH2 Inhibitors Promote β-like Cell Regeneration in T1D Donor tissue

city: Melbourne

first: Assam

last: El-Osta

address: 75 Commercial Road

country: Australia

institute: Baker Heart and Diabetes Institute

summary: β-cells are a type of endocrine cell found in pancreatic islets that synthesize, store and release insulin. Destruction of these cells in type 1 diabetes leads to a lifelong dependence on exogenous insulin administration for survival. Here we employ RNA-seq to examine the promotion of β-like cell regeneration with EZH2 inhibition in pancreatic ductal epithelial cells and exocrine cells isolated from type 1 diabetic donor tissue.

overall_design: Cells treated with EZH2 inhibitors ( Tazemetostat or GSK ) or vehicle control for a total of 48 hours prior to RNA extraction and preparation of RNA sequencing libraries for transcriptomic analysis.

first: Keith

last: Al-Hasani

first: Safiya

middle: N

last: Marikar

first: Harikrishnan

last: Kaipananickal

first: Scott

last: Maxwell

first: Jun

last: Okabe

first: Ishant

last: Khurana

first: Thomas

last: Karagiannis

first: Julia

middle: J

last: Liang

first: Lina

last: Mariana

last: Loudovaris


title: Molecular basis of neurodegeneration in a mouse model of Polr3-related disease

city: Bronx

first: Robyn

middle: D

last: Moir

state: NY

address: 1300 Morris Park Ave

department: Biochemistry

institute: Albert Einstein College of Medicine

type: Non-coding RNA profiling by high throughput sequencing

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

overall_design: Refer to individual Series


title: Molecular basis of neurodegeneration in a mouse model of Polr3-related disease (tRNA)

summary: Pathogenic variants in subunits of RNA polymerase (Pol) III cause a spectrum of neurodegenerative diseases including 4H leukodystrophy. We developed a postnatal whole-body mouse model expressing pathogenic mutations in Polr3a to examine the molecular mechanisms by which reduced Pol III activity results primarily in central nervous system phenotypes. Polr3a mutant mice exhibit behavioral deficits, exocrine pancreatic atrophy and cerebral pathology. Transcriptome and immunohistochemistry analyses of cerebra show a reduction in most Pol III transcripts, induction of innate immune and integrated stress responses and cell type-specific gene expression changes reflecting neuron and oligodendrocyte loss and microglial activation. A global decrease in mature tRNA levels and an altered tRNA profile preceded cerebral neurodegeneration suggesting a causal role in disease initiation. In cerebella, heart and kidney, Pol III transcripts other than tRNAs were generally unaffected. The results suggest tissue-specific thresholds of sensitivity to defects in Pol III transcription.

overall_design: Transcriptome analysis of tamoxifen-induced expression of Polr3a mutation in mouse cerebrum and cerebellum

first: Emilio

last: Merheb

first: Violeta

last: Chitu

first: E

middle: R

last: Stanley

first: Ian

middle: M

last: Willis


title: Gene expression changes upon the ablation of mesenchymal androgen receptor (AR) in the mouse mesonephroi

city: Madison

first: Fei

last: Zhao

state: Wisconsin

address: 2015 Linden Dr

department: Comparative Biosciences

institute: University of Wisconsin-Madison

summary: Wolffian duct maintenance and differentiation is predominantly driven by the androgen action, which is mediated by the androgen receptor (AR). It is well established that the mesenchyme indicates the fate and differentiation of epithelial cells. However, in vivo developmental requirement of mesenchymal AR in Wolffian duct development is still undefined. By designing a mesenchyme-specific Ar knockout (ARKO), we discovered that the loss of mesenchymal Ar led to the bilateral or unilateral degeneration of caudal Wolffian ducts and cystic formation at the cranial Wolffian ducts. Ex vivo culture of ARKO Wolffian ducts invariably resulted in bilateral defects, suggesting that some factor(s) originating from surrounding tissues in vivo might promote Wolffian duct survival and growth even in the absence of mesenchymal Ar. Mechanistically, we found cell proliferation was significantly reduced in both epithelial and mesenchymal compartments; but cell apoptosis was not affected. Transcriptomic analysis by RNA-seq revealed differentially expressed genes associated with morphological and cellular changes in ARKO male embryos (i.e. reduced cell proliferation and decreased number of epithelial cells). Mesenchymal differentiation into smooth muscle cells that are critical for morphogenesis was also impaired in ARKO male embryos. Taken together, our results demonstrate the crucial roles of the mesenchymal AR in Wolffian duct maintenance and morphogenesis in mice.

overall_design:
To investigate the function of mesenchymal AR in Wolffian duct development, we designed a tissue-specific ARKO model, Osr2-Cre; Ar-flox. In this model, we successfully ablated Ar in the mesenchyme of the Wolffian duct before sexual differentiation
We prepared 3 ARKO and 3 control mesonephroi from mouse embryos at embryonic day E14.5. The mesonephroi used in this study did not include mesonephric tubule region.
Tissues were snap frozen and then extracted for RNAs.

first: Jillian

last: Wilbourne

first: Allyssa

last: Fogarty


title: Simultaneous Targeting of Ovarian Cancer and Its Microenvironment Using Stem Cell-Engineered Off-The-Shelf CAR-NKT Cells

city: Los Angeles

first: Wenbin

last: Guo

state: CA

address: 610 Charles E. Young Drive, TLSB 5000

institute: UCLA

summary: Ovarian cancer (OC) poses a significant challenge due to frequent recurrence linked to tumor heterogeneity and an immunosuppressive tumor microenvironment (TME). Targeting both OC cells and TME simultaneously holds promise for effective treatment. This study comprehensively analyzed 17 chemonaive and 18 refractory/recurrent OC samples, identifying mesothelin (MSLN) and natural killer receptor (NKR) ligands as tumor targets and CD1d as an OC TME target. Leveraging hematopoietic stem cell (HSC) gene engineering and feeder-free differentiation culture, we generated allogeneic MSLN-targeting CAR (MCAR)-engineered invariant natural killer T (MCAR-NKT) cells, demonstrating high-yield and high-purity production,potentantitumor efficacy, multiple tumor targeting mechanism, and significant in vivo expansion and persistence. Notably, these cells selectively deplete immunosuppressive TAMs and MDSCs, counteract tumor immune evasion, display a favorable safety profile with low risks of GvHD and CRS, and exhibit a stable “hypoimmunogenic” phenotype attributed to epigenetic and signaling regulations. These findings underscore the preclinical feasibility and therapeutic potential of allogeneic MCAR-NKT cell products for OC, laying a foundation for translational and clinical development.

overall_design:
To comprehensively study the gene expression profile across the allogeneic MCAR-NKT cell populations, we performed and analyzed bulk RNA-Seq of allogeneic MCAR-NKT cells and other immune cells, including 4 AlloMCAR-NKT, 4 Allo15MCAR-NKT, 3 PBMC-NKT, 7 PBMC-Tc, and 2 PBMC-NK. This study sequenced 4 AlloMCAR-NKT, 4 Allo15MCAR-NKT, and 2 PBMC-Tc cell samples. The remaining samples were sequenced in our previous study (GEO Accession: GSE164425), thus we downloaded the raw sequencing data and reanalyzed them. All 20 samples were subject to the same processing and analysis procedure as denoted in the PROTOCOLS section.
Re-analysed Samples PRJNA690603/GSE164425:
GSM5009508 SRR13381422/SRX9804363 SAMN17255538
GSM5009509 SRR13381423/SRX9804364 SAMN17255537
GSM5009510 SRR13381424/SRX9804365 SAMN17255536
GSM5009511 SRR13381425/SRX9804366 SAMN17255535
GSM5009512 SRR13381426/SRX9804367 SAMN17255534
GSM5009496 SRR13381435/SRX9804351 SAMN17255123
GSM5009497 SRR13381436/SRX9804352 SAMN17255122
GSM5009498 SRR13381437/SRX9804353 SAMN17255121
GSM5009499 SRR13381438/SRX9804354 SAMN17255120
GSM5009500 SRR13381439/SRX9804355 SAMN17255119

first: Yan-Ruide

last: Li

first: Zhe

first: Miao

first: Lili

last: Yang


title: Molecular basis of neurodegeneration in a mouse model of Polr3-related disease (RNA)


title: Human Tendon-on-a-Chip for modeling vascular inflammatory fibrosis

city: Rochester

first: Hani

middle: A

last: Awad

address: 601 Elmwood Avenue

department: Biomedical Engineering

institute: University of Rochester

summary: Vascular inflammation and activation of myofibroblasts play crucial roles in the progression of fibrosis. Transforming growth factor beta 1 (TGF-β1) has been identified as a driver of adhesion formation in various tissues, including tendons. However, the mechanisms underlying fibrotic peritendinous adhesions remain poorly understood resulting in a lack of effective therapies. To address this, we developed a novel human Tendon-on-a-Chip (hToC) model, which combines a vascular compartment, with endothelial cells and monocytes, with a tissue compartment containing fibroblasts and tissue-resident macrophages, all in serum-free conditions. Our hToC successfully replicates inflammatory and fibrotic phenotypes observed in mouse models and clinical human samples including myofibroblast differentiation and senescence, tissue contraction, excessive extracellular matrix deposition, and secretion of inflammatory cytokines. We show that fibrosis-on-a-chip is driven by the interaction between the vascular and tissue compartments, including the infiltration of monocytes. Transcriptomics validate the hToC as disease model of diseased human tendon and shows the upregulation of the PI3K/AKT/mTOR pathway—a regulatory nexus of fibrosis in tendon injury. Consistent with this finding, treatment with the mTOR inhibitor Rapamycin suppresses the fibrotic phenotype. Our findings validate the hToC as a tool for investigating human fibrosis and illuminate the underappreciated vascular contribution to tendon pathophysiology.

overall_design: We developed an in vitro human tendon-on-a-chip (hToC) platform quad culture model composed of human primary tenocytes (TCs) and tissue macrophages (tMɸ) in a collagen hydrogel model of injured tendon, combined with human umbilical endothelial cells (ECs) and circulating Monocytes (cMɸ) to model the new vasculature in injured tendon. To introduce patient variability, we used three distinct Mɸ as donor 1, donor 2, and donor 3. All the other cell sources (TCs and ECs) were kept consistent (primary TCs derived from a single patient of hand surgery, and HUVECs were purchased from a commercial source). Since mTOR was a consistent signature of inflammation and fibrosis in the hToC upon the introduction of TGF-β1, we treated the disease devices (TGF-β1 treated hToC) with Rapamycin, an mTOR inhibitor, and compared them with TGF-β1 treated diseased hToC devices ( injured controls). We performed bulk RNA-sequencing of the two-compartment hToC to evaluate the effects of Rapamycin.

first: Raquel

last: Ajalik

first: Rahul

last: Alenchery

first: Isabelle

last: Linares

first: James

last: McGrath

first: Benjamin

last: Miller


title: Human Tendon-on-a-Chip for modeling vascular inflammatory fibrosis II

summary: Vascular inflammation and myofibroblast activation by TGF-β1 are key, yet-to-be-fully-understood pathological processes in fibrosis. Here we report the development of a novel human Tendon-on-a-Chip (hToC) to elucidate the role of TGF-β1 in peritendinous adhesions, a debilitating fibrosis condition affecting flexor tendon, which currently lacks biological therapies. The hToC allows the crosstalk between a vascular compartment harboring endothelial cells and monocytes with a tissue hydrogel compartment containing tendon fibroblasts and macrophages. We find that the hToC replicates in vivo inflammatory and fibrotic phenotypes in preclinical and clinical samples, including myofibroblast differentiation and tissue contraction, excessive ECM deposition, and inflammatory cytokines secretion. We further show the fibrotic phenotypes are driven by the interactions between the vascular and tissue compartments, mediating the transmigration of monocytes. We demonstrate significant overlap in fibrotic transcriptional signatures in the hToC with human tenolysis samples, including the mTOR pathway, a regulatory nexus of fibrosis across various organs. Treatment with Rapamycin suppressed the fibrotic phenotype on the hToC, which validates the hToC as a preclinical alternative for investigating fibrosis and testing therapeutics.

overall_design: We developed an in vitro human tendon-on-a-chip (hToC) platform quad culture model composed of human primary tenocytes (TCs) and tissue macrophages (tMɸ) in a collagen hydrogel model of injured tendon, combined with human umbilical endothelial cells (ECs) and circulating Monocytes (cMɸ) to model the new vasculature in an injured tendon.  Since TGF-β1 was a consistent signature of inflammation and fibrosis in the injured tendons, we treated the disease devices with TGF-β1 and compared them with non-treated hToC devices (controls). We performed bulk RNA-sequencing of the two-compartment hToC to evaluate the effects of TGF-β1.


title: Mucosal and systemic antigen-specific antibody responses correlate with protection against active tuberculosis in nonhuman primates (NAPPA IgA)

first: Jacqueline

middle: M.

last: Achkar

summary:
Increasing evidence supports a role ofthat antibodies in thecan defense protect against active tuberculosis (TB) but knowledge of potentially protective antigens, especially at in the mucosal airways level, is limited. The main objective of this study was to identify antigen-specific airway and systemic immunoglobulin isotype responses that were associated with the outcome of controlled latent Mycobacterium tuberculosis (Mtb) infection (LTBI) compared to uncontrolled infection (TB) in nonhuman primates.
We investigated airway and systemic IgG, IgA, and IgM responses in paired bronchoalveolar lavage and plasma samples prior to and two- and 5-6-months post Mtb infection using an antigen-unbiased approach with Mtb glycan and proteome-wide microarrays

overall_design: In a case-control design, baired bronchoalveolar lavage and plasma in 57 cynomolgus macaques which, following low-dose airway Mtb infection, developed either LTBI or TB.

first: Elise

last: Ishida

first: Devin

middle: T

last: Corrigan

first: Tingting

last: Chen

first: Yanyan

last: Liu

first: Ryung

middle: S

last: Kim

first: Lusheng

last: Song

first: Tara

last: Rutledge

first: D

last: Magee

first: Joshua

last: LaBaer

first: Todd

middle: L

last: Lowary

first: Philana

last: Lin


title: Mucosal and systemic antigen-specific antibody responses correlate with protection against active tuberculosis in nonhuman primates (NAPPA IgG)


title: Expression data from C2C12 myotubes treated with sugarcane top ethanolic extract (STEE) and control C2C12 myotubes.

city: Tsukuba

first: Kengo

last: Iwata

state: Ibaraki

address: 1-1-1 Tennodai

department: Alliance for Research on the Mediterranean and North Africa (ARENA)

country: Japan

institute: University of Tsukuba / Nippo., Co., Ltd.

summary:
The aim of the study was to obtain the data on the changes brought by STEE in in vitro myotubes, with a focus on metabolism and mitochondria, to explore its unknown functional properties. In this study, the transcriptome-wide analysis using microarray was performed, whcih provide insights into the biological and molecular changes induced by STEE.
The microarray allowed us to capture the transcriptome-wide changes induced by STEE in C2C12 myotubes. For example, STEE induced changes in the expression of genes involved in mitochondria activity, fatty acid metabolism, or inflammatory cytokines in C2C12 myotubes.

overall_design: Microarray analysis was performed in duplicates for each samples; STEE treatment groups were set at two concentrations, 30 µg/mL and 50 µg/mL, and exposed to C2C12 myotubes for 6 hours. RNA extraction from control C2C12 myotubes followed the same schedule as the extraction from STEE-treated C2C12 myotubes.


title: Male sex affects type I/type II interferon response of neutrophils during hepatic Amebiasis

city: Hamburg

first: Marco

last: Er Lukowiak

address: Bernhard-Nocht-Straße 74

country: Germany

institute: Bernhard-Nocht-Institute for tropical medicine

summary: Hepatic amebiasis, a serious complication caused by the parasite Entamoeba histolytica, predominantly affects men. Earlier research in the murine disease model indicated that testosterone modulates an intense immune reaction, triggering destructive immunopathological changes in the liver. Inflammatory monocytes expressing proinflammatory chemokines, crucial for neutrophil recruitment, worsen this process. This study examines sex-related variances in neutrophils during hepatic amebiasis in a mouse model. Male subjects exhibited higher levels and recruitment of neutrophils compared to females. Androgens directly contributed to this bias, enhancing neutrophil recruitment and retarding maturation in response to infection. Transcriptomic analysis revealed diminished type I and II interferon-stimulated gene expression and reduced activation pathways in male neutrophils versus female neutrophils. Upon ex-vivo stimulation, female human neutrophils showed higher expression of a key type I interferon-stimulated gene (viperin/RSAD2) at the protein level, which was similar in mice after infection, and suppressed by testosterone. In male mice with hepatic amebiasis, sex-dependent factors led to recruitment of less active neutrophils, intensifying immunopathological damage to liver tissue. This sex disparity and testosterone's impact on interferon-stimulated genes hold implications beyond hepatic amebiasis, potentially influencing broader areas, including viral infectious diseases

overall_design: Bone marrow and blood neutrophils from male and female Entamoeba histolytica infected mice and controls.

last: Er-Lukowiak

first: Sonja

last: Hänzelmann


title: Mucosal and systemic antigen-specific antibody responses correlate with protection against active tuberculosis in nonhuman primates (LAM63 IgG)


title: Transcriptional profiling of human cartilage endplate cells identified novel genes and cell clusters underlying degenerated and non-degenerated phenotypes (scRNA-seq)

city: Columbus

first: Maciej

last: Pietrzak

state: OH

address: 1800 Cannon Drive, 340C Lincoln Tower

department: Department of Biomedical Informatics College of Medicine

institute: Ohio State University

summary: Background: Low back pain is a leading cause of disability worldwide and is frequently attributed to intervertebral disc (IVD) degeneration.  Though the contributions of the adjacent cartilage endplates (CEP) to IVD degeneration are well documented, the phenotype and functions of the resident CEP cells are critically understudied.  To better characterize CEP cell phenotype and possible mechanisms of CEP degeneration, bulk and single-cell RNA-Sequencing of non-degenerated and degenerated CEP cells were performed.  Methods: Human lumbar CEP cells from degenerated (Thompson Grade ≥ 4) and non-degenerated (Thompson Grade ≤ 2) discs were expanded for bulk (N=4 non-degenerated, N=4 degenerated) and single-cell (N=1 non-degenerated, N=1 degenerated) RNA-Sequencing.  Genes identified from bulk RNA-Sequencing were categorized by function and their expression in non-degenerated and degenerated CEP cells were compared.  A PubMed literature review was also performed to determine which genes were previously identified and studied in the CEP, IVD, and other cartilaginous tissues.  For single-cell RNA-Sequencing, different cell clusters were resolved using unsupervised clustering and functional annotation.  Differential gene expression analysis and Gene Ontology, respectively, were used to compare gene expression and functional enrichment between cell clusters, as well as between non-degenerated and degenerated CEP samples.  Results: Bulk RNA-Sequencing revealed 38 genes were significantly upregulated and 15 genes were significantly downregulated in degenerated CEP cells relative to non-degenerated cells (|Fold change| ≥ 1.5).  Of these, only 2 genes were previously studied in CEP cells and 31 were previously studied in the IVD and other cartilaginous tissues.  Single-cell RNA-Sequencing revealed 11 unique cell clusters, including multiple chondrocyte and progenitor subpopulations with distinct gene expression and functional profiles.  Analysis of genes in the bulk RNA-Sequencing dataset showed that progenitor cell clusters from both samples were enriched in “non-degenerated” genes, but not “degenerated” genes.  For both bulk- and single-cell analyses, gene expression and pathway enrichment analyses highlighted several pathways that may regulate CEP degeneration, including transcriptional regulation, translational regulation, intracellular transport, and mitochondrial dysfunction.  Conclusions: This thorough analysis using RNA-Sequencing methods highlighted numerous differences between non-degenerated and degenerated CEP cells, the phenotypic heterogeneity of CEP cells, and several pathways of interest that may be relevant in CEP degeneration.

overall_design: 10x Single Cell RNA Sequencing

first: Kyle

last: Kuchynsky

first: Patrick

last: Stevens

first: Amy

last: Hite

first: William

last: Xie

first: Khady

last: Diop

first: Shirley

last: Tang

first: Safdar

last: Khan

last: Walter

first: Devina

last: Purmessur


title: Expression data from HepG2 hepatocytes treated with sugarcane top ethanolic extract (STEE) and control HepG2 cells.

summary:
The aim of the study was to obtain the data on the changes brought by STEE in in vitro hepatocytes, with a focus on metabolism and mitochondria, to explore its unknown functional properties. In this study, the transcriptome-wide analysis using microarray was performed, whcih provide insights into the biological and molecular changes induced by STEE.
The microarray allowed us to capture the transcriptome-wide changes induced by STEE in HepG2 hepatocytes. For example, STEE induced changes in the expression of genes involved in mitochondria activity, fatty acid metabolism, MAPK signaling, or cAMP signaling in HepG2 hepatocytes.

overall_design: Microarray analysis was performed in duplicates for each samples; STEE treatment groups were set at two concentrations, 15 µg/mL and 30 µg/mL, and exposed to HepG2 cells for 24 hours. RNA extraction from control HepG2 cells followed the same schedule as the extraction from STEE-treated HepG2 cells.


title: Mucosal and systemic antigen-specific antibody responses correlate with protection against active tuberculosis in nonhuman primates

first: Jacqueline

last: Achkar

type:
Protein profiling by protein array
Other

platform_organism:
Homo sapiens
synthetic construct


title: Mucosal and systemic antigen-specific antibody responses correlate with protection against active tuberculosis in nonhuman primates (LAM30 IgM)

first: Elise

last: Ishida

first: Devin

last: Corrigan

first: Tingting

last: Chen

first: Yanyan

last: Liu

first: Ryung

last: Kim

first: Lusheng

last: Song

first: Tara

last: Rutledge

first: D

last: Magee

last: LaBaer

last: Lowary


title: Transcriptional profiling of human cartilage endplate cells identified novel genes and cell clusters underlying degenerated and non-degenerated phenotypes

first: Maciej

last: Pietrzak

overall_design: Bulk mRNA Sequencing

first: Kyle

last: Kuchynsky

last: Stevens

last: Hite

last: Xie

first: Benjamin


title: SUMOylation fine-tunes the transcriptional activity of endothelial HEY1 in the regulation of angiogenesis [HEY1 ChIP-seq]

city: Hangzhou

first: Luyang

last: Yu

address: College of Life Sciences, Zijingang Campus, Zhejiang University, No. 866 Yuhangtang Road, Hangzhou, Zhejiang 310058, China

institute: Zhejiang University

summary: Our previous results from RNA-seq and IP-MS together suggest that SUMOylation may be critical for the DNA-binding capability of HEY1 to enhance its transcriptional repressive activity. To confirm our speculation, we conducted ChIP assays in HUVECs.

overall_design: Samples were from human umbilical vein endothelial cell (HUVECs) infected with adenovirus expressing HEY1-WT/3KR. Egight samples were divided into two groups: HEY1-WT group and HEY1-3KR group. Each group was divided in to "input" (as control) and "ChIP". There were 2 replicates for single experiment.

first: Ruizhe

last: Ren

first: Xiyang

last: Wei


title: SUMOylation fine-tunes the transcriptional activity of endothelial HEY1 in the regulation of angiogenesis

sample_organism:
Homo sapiens
Mus musculus

platform_organism:
Homo sapiens
Mus musculus


title: Effect of doxycycline on the gut microbiome and neuroinflammation

city: Houston

first: Caleb

last: Wood

state: TX

address: 1 Baylor Plaza

institute: Baylor College of Medicine

summary: Abstract: Many mouse models of neurological disease use the tetracycline transactivator (tTA) system to control transgene expression by oral treatment with the broad-spectrum antibiotic doxycycline.  Antibiotic treatment used for transgene control might have undesirable systemic effects, including the potential to affect immune responses in the brain via changes in the gut microbiome.  Recent work has shown that an antibiotic cocktail to perturb the gut microbiome can suppress microglial reactivity to brain amyloidosis in transgenic mouse models of Alzheimer's disease based on controlled overexpression of the amyloid precursor protein (APP). Here we assessed the impact of chronic low dose doxycycline on gut microbiome diversity and neuroimmune response to systemic LPS challenge in a tTA-regulated model of Alzheimer's amyloidosis. We show that doxycycline decreased microbiome diversity in both APP transgenic and wild-type mice and that these changes persisted long after drug withdrawal.  Despite this change in microbiome composition, dox treatment had minimal effect on transcriptional signatures in the brain, both at baseline and following acute LPS challenge. Our findings suggest that central neuroinflammatory responses may be less affected by dox at doses needed for transgene control than by antibiotic cocktail at doses used for microbiome manipulation.

overall_design: Twenty-three RNA samples (extracted from brain cortex) were analyzed. There are 4 experimental groups: Untreated (n=8), Dox (n=4), LPS (n=5), and Dox+LPS (n=6). Untreated mice were never exposed to doxycycline. Dox mice received oral doxycycline treatment in chow (100mg/kg) from neonatal day P3 until 6 weeks of age, followed by 6 weeks of doxycycline washout. LPS mice never received dox treatment and were administered 1 IP LPS injection (2mg/kg) 18 hours before harvest. Dox+LPS mice received oral doxycycline treatment in chow from neonatal day P3 until 6 weeks of age, followed by 6 weeks of doxycycline washout, and then they were administered 1 IP LPS injection (2mg/kg) 18 hours before harvest.

first: Emily

last: Koller

first: Kristi

last: Hoffman

first: Zoe

last: Lai

first: Joanna

last: Jankowsky


title: Nucleolar TAAP1/C22orf46 confers pro-survival signaling  in non-small cell lung cancer

city: Dresden

last: Paszkowski-Rogacz

address: Tatzberg 47/49

department: UCC / Medical Faculty and University Hospital Carl Gustav Carus

institute: Technische Universität Dresden

summary: Tumor cells subvert immune surveillance by harnessing inhibitory signals to acquire immune resistance. Bispecific antibodies have been developed to direct cytotoxic T lymphocytes to the tumor site and foster their activities to reduce tumor immune resistance. Although applied with success, bispecific antibodies are not universally effective partially due to the expression of pro-survival factors by tumor cells. Here, we report a CRISPR/Cas9 screen in human non-small cell lung cancer for genes that confer tumors with increased resistance to T lymphocyte mediated killing. We show that lung carcinoma cells devoid of expression of the gene C22orf46 exhibit increased susceptibility to T cell induced apoptosis and genotoxic stress mediated by chemotherapeutic agents. We present data showing that C22orf46, previously annotated as a non-coding gene, encodes an expressed nucleolar protein with remote homologies to the BH domain-containing Bcl-2 family and propose to name this protein Tumor Apoptosis Associated Protein 1 (TAAP1). Collectively, our findings establish TAAP1/C22orf46 as a pro-survival oncogene with possible implications to therapy

overall_design: RNA-seq transcriptome profiling of wild-type and C22orf46-knockout NCI-H1975 cells, with both genotypes cultured and sequenced in triplicates.

first: Marietta

last: Döring

first: Mirko

last: Theis


title: SUMOylation fine-tunes the transcriptional activity of endothelial HEY1 in the regulation of angiogenesis [MLEC RNA-seq]

summary: To validate the results in primary endothelial cells including HUVECs and HMVECs, the effect of HEY1 SUMOylation on angiogenic functions was examined in MLECs isolated form Hey1 iEC-KO HEY1-WT/3KR iEC-KI mice.

overall_design: Samples were MLECs isolated form Hey1 iEC-KO HEY1-WT/3KR iEC-KI mice. Six samples were divided into two groups:  HEY1-WT iEC-KI group and HEY1-3KR iEC-KI group. There are 3 replicates in each group.


title: Orthotopic CRC organoid transplantation in mice: A novel model for the study and treatment of peritoneal carcinomatosis [Whole-tumour human scRNA-Seq]

city: Freiburg

first: Pierre

middle: Daniel

last: Cauchy

state: Baden-Württemberg

address: Breisacher Str. 115

department: Zentrum für Translationale Zellforschung

institute: University Medical Center Freiburg

summary: Metastasized colorectal cancer (CRC) is associated with a poor prognosis and rapid disease progression. Besides hepatic metastasis, peritoneal carcinomatosis is the major cause of death in UICC stage IV CRC patients. Insights into differential site-specific reconstitution of tumour cells and the corresponding tumour microenvironment are still missing. Here, we analysed the transcriptome of single cells derived from murine multivisceral CRC and gave insight into the inter-metastatic cellular heterogeneity regarding tumour epithelium, stroma and immune cells. Interestingly, we found an intercellular site-specific network of cancer associated fibroblasts and tumour epithelium during peritoneal metastasis as well as an autologous feed-forward loop in cancer stem cells. We furthermore deciphered a metastatic dysfunctional adaptive immunity by a loss of B cell dependent antigen presentation and consecutive effector cell exhaustion. Consequently, we demonstrate the high human-mimicking potential of this murine metastatic CRC model and provide a valid tool for future site-specific preclinical drug testing.

overall_design: scRNA-Seq from human primary tumor (CRC), peritoneal carcinomatisis (PC) and liver metastasis CRC biopsies

first: Christopher

last: Berlin

first: Lisa

last: Marx

first: Bernhard

last: Mauerer

first: Stefan

last: Fichtner-Feigl

first: Laura

last: Miketiuk

first: Marina

last: Pesic

first: Florian

last: Greten

first: Claudia

last: Laessle

first: Jost

last: Lünstedt

first: Naomi

last: Rühl

first: Dominik

last: Jauch

first: Andreas

last: Jud

first: Philipp

last: Holzner

first: Esther

last: Biesel

first: Hannes

last: Neeff

first: Rebecca

last: Kesselring


title: Blastocyst derived signal facilitate the embryo implantation via protein degradation via activating lysosome in the uterine epithelia [RNA-Seq: Epithelium_Igf1r_WT_KO]

city: Xiamen

first: Wenbo

last: Deng

state: Fujian

address: Xiang'an Road

department: School of Medicine

institute: Xiamen University

summary: The mammalian endometrium is covered by the luminal epithelium (Le), which directly interacts with the blastocyst and plays an important role in the establishment of reciprocal crosstalk between the embryo and receptive uterus during implantation. However, the effect of the blastocyst on uterine receptivity is far from well understood. Through transcriptomic profiling of the uterine Le isolated by laser capture microdissection, it was demonstrated that global gene expression changes occurred in Le between pseudopregnant mice without embryos and pregnant mice with embryos. Some differentially expressed genes, including upregulated Areg, Ihh, Lifr and downregulated Msx1, Pgr, Gata2, have been reported to regulate the establishment of uterine receptivity. Besides, we found that blastocysts induced an increase in both the number and acidification of lysosome, consistent with enhanced lysosomal hydrolase activity in uterine Le. Further exploration uncovered that blastocyst-derived IGF2 was involved into the activation of epithelial STAT3 to induce lysosomal hydrolase expression, and inhibition of lysosomal function derails normal uterine receptivity and embryo implantation. Finally, based on the proteomic data of both epithelia and the separated lysosome, it was revealed that CLDN1 and MUC1, two well-known downregulated molecules for successful implantation, are degraded by epithelial lysosome. In brief, our data demonstrated that blastocysts induced normal epithelium differentiation with lysosome activation to promote the establishment of uterine receptivity for embryo implantation.

overall_design: Gene expression of epithelium in WT and Igf1rKO pregnant day 4 uteri


title: SUMOylation fine-tunes the transcriptional activity of endothelial HEY1 in the regulation of angiogenesis [HUVEC RNA-seq]

first: Luyang

last: Yu

summary: Previous studies have shown that HEY1 is a major downstream transducer of NOTCH signaling and transcriptionally represses VEGFR2. We aimed to investigate whether SUMOylation is critical for HEY1-mediated transcriptional regulation of angiogenesis in endothelial cells. To address this question, we performed RNA-seq to assess the repressive landscape of HEY1-WT and HEY1-3KR.

overall_design: Samples were from human umbilical vein endothelial cell (HUVECs) infected with adenovirus expressing HEY1-WT/3KR. Nine samples were divided into three groups: the LacZ group (as control), HEY1-WT group and HEY1-3KR group. There are 3 replicates in each group.

first: Ruizhe

last: Ren

first: Xiyang

last: Wei


title: Blastocyst derived signal facilitate the embryo implantation via protein degradation via activating lysosome in the uterine epithelia

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

overall_design: Refer to individual Series


title: Blastocyst derived signal facilitate the embryo implantation via protein degradation via activating lysosome in the uterine epithelia [RNA-Seq: Epithelium_D4_PsdD4]

overall_design: Gene expression of epithelium in normal day4 or pseduopregnant day 4 uteri


title: NK cell-triggered CCL5/IFN?-CXCL9/10 axis underlies the clinical efficacy of HER2-targeted antibodies in primary HER2 positive breast cancer [RNA-seq]

city: Barcelona

first: Júlia

last: Perera-Bel

address: Doctor Aiguader, 88

department: MARData-BU

country: Spain

institute: Hospital del Mar Research Institute

summary: Tumor-infiltrating (TI)-NK cell numbers predict better than TIL score the efficacy of HER2-targeted antibodies in primary breast cancer patients. To understand the mechanism/s underlying this association, biological processes enriched in NK cell-infiltrated as compared to NK cell-desert HER2-positive breast tumors paired by TIL score were leveraged from transcriptomic data. NK cell-infiltrated tumors were enriched in transcripts regulated by interferons and NF-kB. Among them, levels of CCL5/IFNG-CXCL9/10 positively correlated with the number of TI-NK cells in the original biopsy. Indeed, coordinated expression of CCL5/IFNG-CXCL9/10 transcripts was also evidenced in tumor biopsies from a phase II clinical trial where IFNG levels associated to the achievement of pathological complete response to anti-HER2 antibody treatment (OR 96.3, p=0.01) and correlated with their TI-NK cell score. In in vitro models, anti-HER2 antibody-dependent NK cell activation led to the secretion of CCL5/IFN-? and the subsequent production of IFN-?-dependent CXCL9/10 by bystander breast cancer cells. Ex vivo treatment of breast tumor-derived multicellular cultures with trastuzumab induced the activation of CD16+ TI-NK cells and their conversion into a CD16-CD103+ subpopulation, both endowed with CCL5 and IFN-? producing potential. CD16+ and CD16-CD103+ TI-NK cell subpopulations shared the expression of EOMES, TBX21 and several KIR genes, indicating their lineage relationship; and their proportions positively correlated with total NK cell, CD8+ and tissue-resident T cell frequencies, immune cell subsets with anti-tumor potential. Remarkably, the coordinated induction of CCL5/IFNG-CXCL9/CXCL10 expression, concomitant to the conversion of CD16+ into CD16+/-CD103+ tumor-infiltrating NK cells, was recapitulated in a humanized HER2+ breast cancer in vivo model treated with a combination of anti-HER2 antibodies and in vitro expanded human NK cells, paralleling tumor growth control. Finally, patients achieving good clinical responses to anti-HER2 antibody-based neoadjuvant treatment showed an early and coordinated increase in sera CCL5 and CXCL9/CXCL10 levels which positively correlated with TI-NK cell numbers in the corresponding diagnosis biopsy. Overall, our data point to NK cells as regulators of the tumor microenvironment through the early secretion of CCL5/IFN-? resulting in the production of CXCL9/10 and the recruitment/differentiation of immune infiltrates with anti-tumor potential, ultimately contributing to anti-HER2 antibody clinical efficacy.

overall_design: Paired samples of peripheral blood and treatment-naive breast tumor specimens were obtained from 3 breast cancer patients, blind to their clinicopathological features. Multicellular suspensions from tumors were obtained as described above and stained with directly labelled antibody cocktail including a-CD45-AF700 (clone 2D1), a-CD3-PerCP (clone SK7), a-CD56-APC (clone CMSSB), a-CD16-efluor780 (clone CB16), a-CD103-FITC (Clone B-Ly7) and DAPI as a viability die. Distinct tumor-infiltrating NK cell subsets were sorted based on the expression of CD16 and CD103 (CD16+; CD16-CD103+; CD16-CD103-) from the CD56+ CD3 gate in CD45+ DAPI- lymphocytes. Peripheral blood NK cells were sorted from PBMC based on their CD56bright CD16- and CD56dim CD16+ expression profile. Cell sorting was performed in a Influx sorter ( BD, YYY) at the Flow Cytometry Facility, PRBB, Barcelona.

first: Aura

last: Muntasell

first: Sara

last: Santana-Hernßndez

first: Joan

last: Albanell


title: NK cell-triggered CCL5/IFNg-CXCL9/10 axis underlies the clinical efficacy of HER2-targeted antibodies in primary HER2-positive breast cancer [array]

summary: Tumor-infiltrating (TI)-NK cell numbers predict better than TIL score the efficacy of HER2-targeted antibodies in primary breast cancer patients. To understand the mechanism/s underlying this association, biological processes enriched in NK cell-infiltrated as compared to NK cell-desert HER2-positive breast tumors paired by TIL score were leveraged from transcriptomic data. NK cell-infiltrated tumors were enriched in transcripts regulated by interferons and NF-kB. Among them, levels of CCL5/IFNG-CXCL9/10 positively correlated with the number of TI-NK cells in the original biopsy. Indeed, coordinated expression of CCL5/IFNG-CXCL9/10 transcripts was also evidenced in tumor biopsies from a phase II clinical trial where IFNG levels associated to the achievement of pathological complete response to anti-HER2 antibody treatment (OR 96.3, p=0.01) and correlated with their TI-NK cell score. In in vitro models, anti-HER2 antibody-dependent NK cell activation led to the secretion of CCL5/IFN-ɣ and the subsequent production of IFN-ɣ-dependent CXCL9/10 by bystander breast cancer cells. Ex vivo treatment of breast tumor-derived multicellular cultures with trastuzumab induced the activation of CD16+ TI-NK cells and their conversion into a CD16-CD103+ subpopulation, both endowed with CCL5 and IFN-ɣ producing potential. CD16+ and CD16-CD103+ TI-NK cell subpopulations shared the expression of EOMES, TBX21 and several KIR genes, indicating their lineage relationship; and their proportions positively correlated with total NK cell, CD8+ and tissue-resident T cell frequencies, immune cell subsets with anti-tumor potential. Remarkably, the coordinated induction of CCL5/IFNG-CXCL9/CXCL10 expression, concomitant to the conversion of CD16+ into CD16+/-CD103+ tumor-infiltrating NK cells, was recapitulated in a humanized HER2+ breast cancer in vivo model treated with a combination of anti-HER2 antibodies and in vitro expanded human NK cells, paralleling tumor growth control. Finally, patients achieving good clinical responses to anti-HER2 antibody-based neoadjuvant treatment showed an early and coordinated increase in sera CCL5 and CXCL9/CXCL10 levels which positively correlated with TI-NK cell numbers in the corresponding diagnosis biopsy. Overall, our data point to NK cells as regulators of the tumor microenvironment through the early secretion of CCL5/IFN-ɣ resulting in the production of CXCL9/10 and the recruitment/differentiation of immune infiltrates with anti-tumor potential, ultimately contributing to anti-HER2 antibody clinical efficacy.

overall_design: Gene expression microarray analysis were performed by the MARGenomics core facility at Hospital del Mar Medical Research Institute, Barcelona. Total RNA was isolated (RNeasy® Micro Kit, Qiagen) from 3 sequential, 10 µm thick, FFPE breast carcinoma sections from 6 TI-NK cell positive and 6 TI-NK cell negative biopsies. Tumors were selected from a previously described cohort, based on double CD3 CD56 immunohistochemistry data (Muntasell A CCR, 2019). Amplification, labelling, and hybridization was performed according to protocol GeneChip WT PLUS Reagent kit (P/N 703174 2017) and hybridized to Human Clariom S Array (Thermo Fisher Scientific). For analysis, R programming (Version 3.4.3) Bioconductor and the Comprehensive R Archive Network (CRAN 2017) packages were used. Samples were background corrected, quantile-normalized and summarized to a gene-level using the robust multi-chip average (RMA). An empirical Bayes moderated t-statistics model (LIMMA) adjusted by Estrogen Receptor status was built to detect differentially expressed genes with a p-value<0.05 and a fold-change>1.5. Data represented in heatmaps was scaled by genes  using the z-score normalization. Analysis of biological pathways enriched in TI-NK cell positive biopsies and major regulators of enriched genes was performed uploading upregulated DEG into IPA software.

last: Santana-Hernández


title: Autophagy induces hair follicle stem cell activation and hair follicle regeneration by regulating glycolysis

city: Guangzhou

first: Zhan

last: Wang

state: Guangdong

address: No.1023,South Shatai Road, Baiyun District

department: Nanfang   Hospital, Southern Medical University/The First School of Clinical Medicine,   Southern Medical University

institute: Southern Medical University

summary: In this study, in order to explore the role of autophagy of human hair follicle stem cells in hair growth, we explored new ideas for hair regrowth. In this study, rapamycin was used to treat hair follicle stem cells to promote autophagy, and the different expression of genes was observed by comparing with the blank control group.

overall_design: Detection of RNA expression after rapamycin and blank control treatment of human hair follicle stem cells.

first: Pingping

last: Sun

first: Kaitao

last: Li

first: Yong

last: Miao


title: Gene expression of p53 deficient, mutant p53R245W, and wildtype murine livers from animals fed a high fat, choline defficient diet

first: Xiaoping

last: Su

state: Texas

address: 7300 Brompton St, Apt 5633

institute: MD Anderson Cancer Center

summary: We conducted gene expression analysis from total livers of animals with different genotypes isolated 3 months after placement on diet

overall_design: RNA sequencing analysis was conducted on p53 deficient, mutant p53R245W, and wildtype murine livers fed on high fat, choline defficient diet for 3 months

first: Denada

last: Dibra

first: Guillermina

last: Lozano


title: NK cell-triggered CCL5/IFNg-CXCL9/10 axis underlies the clinical efficacy of HER2-targeted antibodies in primary HER2-positive breast cancer


title: Mucosal and systemic antigen-specific antibody responses correlate with protection against active tuberculosis in nonhuman primates (LAM63 IgA)

first: Jacqueline

last: Achkar

summary:
Increasing evidence supports a role ofthat antibodies in thecan defense protect against active tuberculosis (TB) but knowledge of potentially protective antigens, especially at in the mucosal airways level, is limited. The main objective of this study was to identify antigen-specific airway and systemic immunoglobulin isotype responses that were associated with the outcome of controlled latent Mycobacterium tuberculosis (Mtb) infection (LTBI) compared to uncontrolled infection (TB) in nonhuman primates.
We investigated airway and systemic IgG, IgA, and IgM responses in paired bronchoalveolar lavage and plasma samples prior to and two- and 5-6-months post Mtb infection using an antigen-unbiased approach with Mtb glycan and proteome-wide microarrays

overall_design: In a case-control design, baired bronchoalveolar lavage and plasma in 57 cynomolgus macaques which, following low-dose airway Mtb infection, developed either LTBI or TB.

first: Elise

last: Ishida

first: Devin

last: Corrigan

first: Tingting

last: Chen

first: Yanyan

last: Liu

first: Ryung

last: Kim

first: Lusheng

last: Song

first: Tara

last: Rutledge

first: D

last: Magee

first: Joshua

last: LaBaer

first: Todd

last: Lowary

first: Philana

last: Lin


title: Bivalent activity of super-enhancer RNA LINC02454 controls 3D chromatin structure and regulates glioma sensitivity to temozolomide.

city: Tianjin

first: Niannian

last: Li

state: Tianjin

address: No. 94 Weijin Road, Nankai District, Tianjin

department: college of Life Sciences

institute: Nankai University

summary: Temozolomide (TMZ) resistance of glioma cells is currently a critical problem in glioma clinical treatment. In this study, we reveal a bivalent function of a super-enhancer RNA LINC02454 in modulating glioma cell sensitivity to TMZ via regulation of SORBS2 and DDR expression. LINC02454 increased TMZ sensitivity by maintaining 3D chromatin structure and promoting SORBS2 expression, but paradoxically decreased TMZ sensitivity by binding to the DDR1 locus and promoting DDR1 transcription. This study proposes a new regulatory mechanism governing glioma cell sensitivity to TMZ and provides new insights that may improve therapies against glioma.

overall_design: 2 biological replicates were analyzed for U251 or U87 by RNA-seq in TMZ-treated  cells for 72 h, 2 biological replicates were analyzed for LINC02454 SE KO cells, LINC02454 KD cells and LINC02454 OE cells by RNA-seq, 2 biological replicates of H3K27Ac ChIP-seq for U251 lines, 2 biological replicates were analyzed for U251 lines by Capture-C.

first: Lu

last: wange

first: Shi

last: Tengfei

first: Guo

last: Dianhao

first: Wang

last: Wenbin

first: Zhang

last: lei


title: CircTBC1D22A inhibits the progression of colorectal cancer through autophagy regulated via miR-1825/ATG14 axis

status: Public on Jan 11 2024

first: Jingbo

last: Sun

state: Guangdong Province

address: No. 1023-1063, Shatai South Road, Baiyun District

institute: School of Basic Medical Sciences, Southern Medical University

summary: Distant metastasis is the main cause of death in patients with colorectal cancer (CRC). A better understanding of the mechanisms of metastasis can greatly improve the outcome of patients with CRC. Accumulating evidence suggests that circRNA plays pivotal roles in cancer progression and metastasis, especially acting as a miRNA sponge to regulate the expression of the target gene. Public database bioinformatics analysis found that miR-1825 was highly expressed in CRC tissues. In this study, miR-1825 was highly expressed in CRC tissues, which was positively correlated with lymph node metastasis and distant metastasis. In vitro and in vivo experiments confirmed that miR-1825 was positively correlated with the proliferation and migration of CRC cells. This event can be inhibited by circTBC1D22A. CircTBC1D22A can directly interact with miR-1825 and subsequently act as a miRNA sponge to regulate the expression of target gene ATG14, which collectively advances the autophagy-mediated progression and metastasis of CRC.

overall_design: To identify potential ceRNAs for miR-1825 in CRC, circRNA-seq was performed using six CRC tissues that were divided into high miR-1825 expression and low miR-1825 expression. Of these, 100 circRNAs were elevated, and 78 circRNAs were reduced.

first: Hongmei

last: Wu

first: Junjie

last: Luo

first: Yue

last: Qiu

first: Yangwei

last: Xu

first: Lixin

first: Xiaolong

first: Qingling

last: Zhang


title: Interleukin-26 potentiates type 2 skin inflammation in presence of interleukin-1β

city: Basel

first: Katharina

last: Bier

address: Lichtstrasse

department: Immunology

country: Switzerland

institute: Novartis Institutes for Biomedical Research

summary: Atopic dermatitis (AD) is a debilitating inflammatory skin disorder. Biologics targeting the IL-4/IL-13 axis are effective in AD, but there is still a large proportion of patients that do not respond to IL-4R blockade. Further exploration of potentially pathogenic T cell-derived cytokines in AD may lead to new effective treatments. This study aimed to investigate the downstream effects of IL-26 on skin in the context of type 2 skin inflammation. We found that IL-26 alone exhibited limited inflammatory activity in skin. However, in presence of IL-1β, IL-26 potentiated the secretion of TSLP, CXCL1 and CCL20 from human epidermis through JAK/STAT signaling. Moreover, in an in vivo AD-like skin inflammation model, IL-26 exacerbated skin pathology and locally increased type 2 cytokines, most notably of Il13 in skin T helper cells. Neutralization of IL-1β abrogated IL-26-mediated effects, indicating that the presence of IL-1β is required for full IL-26 downstream action in vivo. These findings suggest that the presence of IL-1β enables IL-26 to be a key amplifier of inflammation in the skin. As such, IL-26 may contribute to the development and pathogenesis of inflammatory skin disorders such as AD.

overall_design: Gene expression profiling analysis of RNA-seq data from samples obtained from mouse ear skin. Mice were chronically treated every 2-3 days for 17 days with 1.5 nmol MC903. Additionally, mice were treated i.p. with 10 mg/kg anti IL-1b or IgG control antibody every 5 days. Moreover, 200 ng recombinant human IL-26 or BSA as a control was injected into the ear skin of mice every 2 days.

first: Zuzana

last: Senajova

first: Fanny

last: Henrion

first: Yichen

last: Wang

first: Sandro

last: Bruno

first: Celine

last: Rauld

first: Lisa

middle: C

last: Hörman

first: Carmen

last: Barske

first: Sebastian

last: Bergling

first: Marc

last: Altorfer

first: Jasmin

last: Hägele

first: Judith

last: Knehr

first: Tobias

last: Junt

first: Ben

last: Roediger

first: Till

last: Röhn

first: Frank

last: Kolbinger


title: ABCB1 amplification drives paclitaxel resistance in PDAC cells, which can be targeted by novel drug combination strategies

city: Amsterdam

first: Elisa

last: Giovannetti

address: de boelelaan

country: Netherlands

institute: Amsterdam UMC

summary: This study investigate PDAC resistance to paclitaxel.

overall_design: Comparative gene expression profiling analysis of RNA-seq data for Patu-T, Suit.2-028 and Patu-T and Suit.2-028 resistant to gemcitabine or paclitaxel cell lines

first: Alessandro

last: Gregori

first: Cecilia

last: Bergonzini

first: Mjriam

last: Capula

first: Giulia

last: Mantini


title: APOE-NOTCH Axis Governs Elastogenesis During Human Cardiac Valve Remodeling

city: Palo Alto

first: Yu

last: Liu

address: 1215 Welch Road

department: CVI

institute: Stanford University

summary: Valve remodeling is a complex process involving extracellular matrix organization, development of trilaminar structures, and physical elongation of valve leaflets. However, the cellular and molecular mechanisms regulating valve remodeling and their roles in congenital valve disorders remain poorly understood. Semilunar valves and atrioventricular valves from healthy and age-matched human fetal hearts with pulmonary stenosis (PS) were collected. Single-Cell RNA-sequencing (scRNA-seq) was performed to determine the transcriptomic landscape of multiple valvular cell subtypes in valve remodeling and disease. Spatial localization of newly-identified cell subtypes was determined via immunofluorescence and RNA in situ hybridization. The molecular mechanisms mediating valve development was investigated utilizing primary human fetal valve interstitial cells (VICs) and endothelial cells (VECs). scRNA-seq analysis of healthy human fetal valves identified a novel APOE+ elastin-producing VIC subtype (Elastin-VIC) spatially located underneath VECs sensing the unidirectional flow. Knockdown of APOE in fetal VICs resulted in significant elastogenesis defects. In pulmonary valve with PS, we observed decreased expression of APOE and other genes regulating elastogenesis such as EMILIN1 and LOXL1, as well as elastin fragmentation. These findings suggested the crucial role of APOE in regulating elastogenesis during valve remodeling. Furthermore, cell-cell interaction analysis revealed that JAG1 from unidirectional VECs activates NOTCH signaling in Elastin-VICs through NOTCH3. In vitro Jag1 treatment in VICs increased the expression of elastogenesis-related genes and enhanced contractile functions with related gene expression. This was accompanied by activation of NOTCH signaling and elastogenesis observed in VICs co-cultured with VECs in the presence of unidirectional flow. Notably, we found that the JAG1-NOTCH3 signaling pair was drastically reduced in the PS valves. Lastly, we demonstrated that APOE is indispensable for JAG1-induced NOTCH activation in VICs, reinforcing the presence of a synergistic intrinsic and external regulatory network involving APOE and NOTCH signaling that is responsible for regulating elastogenesis during human valve remodeling. scRNA-seq analysis of human fetal valves identified a novel Elastin-VIC subpopulation, and revealed mechanism of intrinsic APOE and external NOTCH signaling from VECs sensing unidirectional flow in regulating elastogenesis during valve remodeling. These mechanisms may contribute to the pathogenesis of elastic malformation in congenital valve disease.

overall_design:
scRNA-seq analysis of four human fetal valves, and comparison between healthy pulmonary valve and age-matched malformed pulmonary valve were also performed.

***RAW data not provided for GSM7134268 due to patient privacy concerns***

first: Ziyi

first: Yifei

last: Miao

first: Mingxia

last: Gu


title: Folfirinox-dependent reprogramming of macrophages by primary pancreatic cancer CAFs

city: Marseille

first: Ghislain

last: BIDAUT

address: 27 Bd Leï Roure

department: Bioinformatics

country: France

institute: Centre de Recherche en Cancérologie de Marseille

summary: The pancreatic cancer tumor microenvironment is dominated primarily by cancer-associated fibroblasts (CAFs) and tumor associated macrophages (TAMs). The interecellular dialogue between CAFs and TAMs and the resulting impact on chemoresistance, specifically to Folfirinox, remains poorly understood. In this study, we sought to understand the impact of primary PDAC CAFs on macrophage reprogramming in a folfirinox-dependent manner and performed various cellular assays (viability, immunophenotyping, phagocytosis, secretory profile analysis) and transcriptomic analysis.

overall_design: We established indirect cocultures, using transwell inserts, between primary pancreatic cancer (PDAC) CAFs and in vitro polarized M2 macrophages and subjected them to folfirinox treatment. Resulting macrophages were analyzed for their transcriptomic profile.

first: Zainab

last: Hussain

first: Thomas

last: Bertran

last: Bidaut

first: Eugenie

last: Lohmann

first: Moacyr

last: Rego

first: Richard

last: Tomasini


title: To investigate the downstream target gene of YAP1 in enzalutamide-resistant (EnzaR) cells and the effects of extracellular vehicles (EVs) derived from EnzaR cells on enzalutamide-sensitive cells by next-generation sequencing analyses

status: Public on Jan 13 2024

city: Tainan

first: Shih-Chieh

last: Lin

address: No.1, University Road

department: Institute of Basic Medical Sciences

country: Taiwan

institute: College of Medicine, National Cheng Kung University

summary: Our study has identified that yes-associated protein 1 (YAP1) is overexpressed in enzalutamide-resistant (EnzaR) cells. Furthermore, enzalutamide-induced YAP1 expression is mediated through the function of chicken ovalbumin upstream promoter transcription factor 2 (COUP-TFII) at the transcriptional and the post-transcriptional levels. Furthermore, both YAP1 and COUP-TFII have proven to be cargoes of EVs by our study. Next, treatment with EnzaR-EVs induces the abilities of enzalutamide resistance in its parental cells while depletion of YAP1 or COUP-TFII in EnzaR-EVs attenuated it. In order to systemically investigate the downstream target gene of YAP1 and the expression profiles changed by EnzaR-EVs from control, YAP1 and COUP-TFII depletions in prostate cancer cells, we have performed RNA-seq analyses to pursuit the research directions of those questions.

overall_design: RNA samples were isolated from EnzaR cells treated with siRNA against YAP1 and control siRNA (n=2), and from LNCaP cells treated without or with control, YAP1- and COUP-TFII-depleted EnzaR-EVs (n=1) for 48 hours.

first: Shih


title: Designing a single cell ATAC-Seq (scATAC-Seq) dataset to benchmark scATAC-Seq analysis methods

city: Parkville

first: Matthew

last: Ritchie

state: Victoria

address: 1G Royal Parade

institute: The Walter and Eliza Hall Institute of Medical Research

summary: Single cell sequencing technology has been widely used for understanding the heterogeneity of complex tissue and for identifying novel cell types or cell states. Previous efforts of single cell profiling are mostly performed by measuring transcriptomes using single cell RNA sequencing (scRNA-seq). scRNA-seq is relatively well developed and around 500 analysis tools are currently available for performing different tasks. In the past five years, assays for profiling the single cell chromatin accessibility landscape have emerged and provide extra information about gene regulation at the epigenetic level. Due to its simplicity and sensitivity, single cell Assays for Transposase-Accessible Chromatin using sequencing (scATAC-seq) is widely used to obtain chromatin accessibility. This data will be used to comprehensively evaluate scATAC-seq data analysis tools and gaps in analysis workflows together with publicly available bulk ATAC-Seq and scATAC-seq data using optimised universal evaluation metrics.

overall_design: Our experiment utilized the 5 human lung adenocarcinoma cell lines H2228, H1975, A549, H838 and HCC827. For the single cell designs, the five cell lines were mixed equally and processed by 10X Chromium.

first: Haoyu

last: Yang

first: Shanika

last: Amarasinghe

first: Daniel

last: Brown

middle: E

first: Mei

last: Du


title: DICER regulation by an USP7-MDM2 axis in cancer cells

city: Shanghai

first: Jianxiu

last: Yu

address: Room 202, Building 7, 280 South Chongqing Road

department: Department of Biochemistry and Molecular Cell Biology

institute: Shanghai Jiao Tong University school of medicine

summary: DICER is an RNase III enzyme which plays a critical role in the microRNA mature process in the cytoplasm, but also is involved in other functions such as chromatin remodeling, epigenetic modification and DNA damage repair in the nucleus. The expression of DICER is almost decreased across the board in human cancers, which highlights that its expression is strictly controlled, however the underlying mechanisms still remain unknown. In this study, we find that deubiquitinase USP7 suppresses the expression of DICER at the protein level, which impacts DNA damage response (DDR) and cancer progression. MDM2, which is a well-known oncoprotein and also a substrate of USP7, is identified as a novel DICER ubiquitin E3 ligase, thus forming a new regulatory axis of USP7-MDM2-DICER. These findings may provide a new approach to the diagnosis, treatment and prognosis of malignant tumors.

overall_design: mRNA expression profiles and miRNA expression profiles in MDA-MB-231/DU145 stable cell lines

first: Xiaojia


title: Effect of a noval UHRF1-Targeted compound H93  on gene expression of DU145 prostate cancer cells.

first: Xiong

last: Li

address: 19 Nonglinxia Road

institute: Guangdong Pharmaceutical University

summary:
To investigate the anti-tumor function of compound H93 in the development of prostate cancer, we treated DU145 cell lines with H93, SAHA or DMSO.
We then performed gene expression profiling analysis using data obtained from RNA-seq of cells after treatment.

overall_design: Comparative gene expression profiling analysis of RNA-seq data for H93-treated DU145 cells and control (treated by SAHA or DMSO) with 3 replications each group.

first: Yuxin

last: Fu

first: Longying

last: Jiang

first: Guojian

last: Xie

first: Yuchong

last: Peng

first: Yongming

first: Qianling

last: Zhu

first: Youhong

last: Liu

first: Xueke

first: Yongheng

last: Chen


title: Effect of a noval UHRF1-Targeted compound H93 on epigenome of DU145 prostate cancer cells.

type: Methylation profiling by genome tiling array

summary:
To investigate the anti-tumor function of compound H93 in the development of prostate cancer, we treated DU145 cell lines with H93, SAHA or DMSO.
We then performed genome wide DNA methylation profiling analysis of cells after treatment. The Illumina Infinium MethylationEPIC BeadChip (850K BeadChip) was used to obtain DNA methylation profiles across approximately 850,000 CpGs.

overall_design: Bisulphite converted DNA from the 9 samples were analyzed. The groups were H93-treated DU145 cells,  reference samples (treated by SAHA) and control samples (treated by DMSO) with 3 replications each group.


title: Circ_0021350 plays an oncogene role by regulating miR-1207-3p/ PIK3R3 in glioblastoma

city: Changchun

first: Liang

last: Han

address: Xiantai Street 126

institute: China-Japan Union Hospital of Jilin University

summary: To screen differentially expressed circRNAs in GBM, we performed RNA-seq using four tumor tissues from patients with GBM and four normal brain tissues and focused on circ_0021350, which is upregulated in GBM.

overall_design: Comparative gene expression profiling analysis of RNA-seq data for GBM tissues and normal brain tissues

first: Cheng

last: Tan

first: Jun

last: Wei

first: Zhaohui

last: Tian

first: Zhengming

last: Wang

first: Guan

first: Yu


title: Inhibitory effect of shikonin on lung cancer cells

city: xi'an

first: wu

last: dan

address: xinsilu

institute: tangdu

summary:
To investigate the effect of shikonin on the proliferation and migration of lung cancer cells, we used shikonin  treated with A549 and H1299 cells
We then performed gene expression profiling using RNA-seq data from A549 cells.

overall_design: Comparative gene expression profiling of RNA-seq data from A549 cells in the treated and non-treated groups.

first: Yujia

last: Zhao

first: Ying

last: Liang

first: Dan

last: Wu


title: RNAseq comparison of gene expression profiles in Hand2-Cre driven Msx1/Msx2 double conditional mutant and control mouse embryonic mandible

city: Cincinnati

first: Rulang

address: 3333 Burnet Ave

department: Division of Developmental Biology

institute: Cincinnati Children's Hospital Medical Center

summary: The mandible of the jawed vertebrate is derived from the mandibular process of the first pharyngeal arch of the early embryo. The first pharyngeal arch consists of cells from all three germ layers, with the neural crest giving rise to all the skeletal elements of the mandible. The correct patterning of the neural crest cells by spatially and temporally controlled expression of various transcription factors during mandible development is crucial for the proper morphogenesis of the lower jaw. Msx family genes encode transcription factors which contain the conserved homeodomain. Among the three members of Msx genes, Msx1 and Msx2 are expressed in the neural crest and epithelium of distal mandibular process during early embryonic development with partially overlapped expression patterns. Msx1-/- mouse embryos develop multiple craniofacial developmental defects including tooth agenesis, cleft palate, and hypoplastic mandible. Although no jaw defects were observed in Msx2-/- mouse embryos, Msx1-/-Msx2-/- mouse embryos exhibit significantly severer mandibular defects compared to Msx1-/- mouse embryos, suggesting a partial functional redundancy between the two genes in mandible development. Besides the direct roles of Msx1 and Msx2 in the development of the mandibular neural crest, the phenotypes of Msx1-/-Msx2-/- may also contributed by secondary impacts from defective pre-migrative neural crest and non-neural crest tissues. Here we performed the gene expression profiling by RNA-seq in the distal mandibular processes of Msx1f/f;Msx2f/f;Hand2-Cre and Msx1f/+;Msx2f/f;Hand2-Cre embryos at E10.75, the former developed distally truncated mandible at later stages while the latter served as morphologically normal littermate control. Comparing the gene expression profiles of the two will give us insight into the functions of Msx1 and Msx2 expressed in mandibular neural crest cells in the development of the mandible.

overall_design: Msx1f/f;Msx2f/f;Rosa26mTmG/mTmG female mice were crossed with Msx1f/+;Msx2f/f;Hand2-Cre males. The embryos were collected at E10.75. The GFP+ embryos were collected and the GFP+ distal mandibles were dissected in cold PBS under fluorescent microscope and snap frozen. A total of 3 litters of embryos were dissected. From each litter, 1 embryo of Msx1f/f;Msx2f/f;Rosa26mTmG/+;Hand2-Cre genotype and 1 embryo of Msx1f/+;Msx2f/f;Rosa26mTmG/+;Hand2-Cre genotype were selected for total RNA extraction, sequencing library preparation, and paired-ended sequencing.

first: Zhaoming


title: Orthotopic CRC organoid transplantation in mice: A novel model for the study and treatment of peritoneal carcinomatosis [Whole-tumor scRNA-Seq]

first: Pierre

last: Cauchy

address: Breisacher Str. 115

institute: University Medical Center Freiburg

summary: Metastasized colorectal cancer (CRC) is associated with a poor prognosis and rapid disease progression. Besides hepatic metastasis, peritoneal carcinomatosis is the major cause of death in UICC stage IV CRC patients. Insights into differential site-specific reconstitution of tumor cells and the corresponding tumor microenvironment are still missing. Here, we analysed the transcriptome of single cells derived from murine multivisceral CRC and gave insight into the inter-metastatic cellular heterogeneity regarding tumor epithelium, stroma and immune cells. Interestingly, we found an intercellular site-specific network of cancer associated fibroblasts and tumor epithelium during peritoneal metastasis as well as an autologous feed-forward loop in cancer stem cells. We furthermore deciphered a metastatic dysfunctional adaptive immunity by a loss of B cell dependent antigen presentation and consecutive effector cell exhaustion. Consequently, we demonstrate the high human-mimicking potential of this murine metastatic CRC model and provide a valid tool for future site-specific preclinical drug testing.

overall_design: scRNA-Seq from organoid-derived whole primary tumor (PT), peritoneal carcinomatisis (PC) and liver metastasis (LM) CRC murine models

first: Christopher

last: Berlin

first: Lisa

last: Marx

first: Bernhard

last: Mauerer

first: Stefan

last: Fichtner-Feigl

first: Laura

last: Miketiuk

first: Marina

last: Pesic

first: Florian

last: Greten

first: Claudia

last: Laessle

first: Jost

last: Lünstedt

first: Naomi

last: Rühl

first: Dominik

last: Jauch

first: Andreas

last: Jud

first: Philipp

last: Holzner

first: Esther

last: Biesel

first: Hannes

last: Neeff

first: Rebecca

last: Kesselring


title: Venomous gland transcriptome and venom proteomic analysis of the scorpion Androctonus amoreuxi reveal new peptides with anti-SARS-CoV-2 activity

city: Aberdeen

first: Centre for Genome-Enabled Biology and Medicine

last: on behalf of listed contributors

state: Aberdeenshire

address: 23 St Machar Drive

department: CGEBM

country: United Kingdom

institute: University of Aberdeen

summary: The recent COVID-19 pandemic shows the critical need for novel broad spectrum antiviral agents. Scorpion venoms are known to contain highly bioactive peptides, several of which have demonstrated strong antiviral activity against a range of viruses. We have generated the first annotated reference transcriptome for the Androctonus amoreuxi venom gland and used high performance liquid chromatography, transcriptome mining, circular dichroism and mass spectrometric analysis to purify and characterize twelve previously undescribed venom peptides. Selected peptides were tested for binding to the receptor-binding domain (RBD) of the SARS-CoV-2 spike protein and inhibition of the spike RBD – human angiotensin-converting enzyme 2 (hACE2) interaction using surface plasmon resonance-based assays. Seven peptides showed dose-dependent inhibitory effects, albeit with IC50 in the high micromolar range (117–1202 μM). The most active peptide was synthesized using solid phase peptide synthesis and tested for its antiviral activity against SARS-CoV-2 (Lineage B.1.1.7). On exposure to the synthetic peptide of a human lung cell line infected with replication-competent SARS-CoV-2, we observed an IC50 of 200 nM, which was nearly 600-fold lower than that observed in the RBD – hACE2 binding inhibition assay. Our results show that scorpion venom peptides can inhibit the SARS-CoV-2 replication although unlikely through inhibition of spike RBD – hACE2 interaction as the primary mode of action. Scorpion venom peptides represent excellent scaffolds for design of novel anti-SARS-CoV-2 constrained peptides. Future studies should fully explore their antiviral mode of action as well as the structural dynamics of inhibition of target virus-host interactions.

first: Ahmad

last: Ghazal

first: David

last: Clarke

first: Mohamed

last: Abdel-Rahman

first: Antonio

last: Ribeiro

first: Elaina

last: Collie-Duguid

first: Craig

last: Pattinson

first: Kate

last: Burgoyne

first: Taj

last: Muhammad

first: Sanad

last: Alfadhel

first: Zeynab

last: Heidari

first: Reham

last: Samir

first: Mariam

last: Gerges

first: Istifanus

last: Nkene

first: Rosa

last: Colamarino

first: Karolin

last: Hijazi

first: Wael

last: Houssen


title: Quantseq 3'mRNA-seq in LESCs from WT and TXNIP-/- mice

city: Daejeon

first: Eun Bok

last: Baek

address: 99 Daehak-ro

country: South Korea

institute: Chungnam National University

summary: RNA samples were collected from LSECs isolated from TXNIP-/- and WT mice. High-throughput sequencing was performed as single-end 75 sequencing using NextSeq 550.

overall_design: High-throughput sequencing was performed as single-end 75 sequencing using NextSeq 550 in LSECs isolated from TXNIP-/- and WT mice

first: Eunhye

last: Jung

first: Eun-Bok

first: Young-Suk

last: Won

first: Hyo-Jung

last: Kwon


title: Low dose ribosomal DNA P-loop mutation affects development and enforces autophagy in Arabidopsis

city: Greifswald

first: Stefan

last: Simm

address: Walter-Rathenau-Straße 48

institute: University Medicine Greifswald

summary: To investigate the ribosomal RNA subpopulation types in a mutant created by CRISPR-Cas9 editing of rDNA copies in Arabidopsis thaliana / Original Abstract: Arabidopsis contains hundreds of ribosomal DNA copies organised within the nucleolar organising regions (NORs) in chromosomes 2 and 4. There are four major types of variants of rDNA, VAR1-4, based on the polymorphisms of 3' external transcribed sequences. The variants are differentially expressed during plant development. We created a mutant by the CRISPR-Cas9-mediated excision of ~25 nt from only the copies of NOR4 ribosomal DNA, obtaining mosaic mutational events on ~5% of all rDNA copies. The excised region consists of P-loop and Helix-82 segments of 25S rRNA. The mutation led to allelic, dosage-dependent defects marked by lateral root inhibition, reduced size, and pointy leaves, all previously observed for defective ribosomal function. The mutation in NOR4 led to dosage compensation from the NOR2 copies, marked by its associated single-nucleotide variants and, thus, resulted in an altered rRNA sub-population. Furthermore, it caused rRNA maturation defects specifically in the minor pathway characterised by 32S pre-rRNA accumulation. The mutated rRNAs were not incorporated into the translating ribosomes, while it induced an elevated autophagic flux, likely related to ribophagy.

overall_design: Comparative rRNA expression profiling of BG wildtype and homozygous ploop KD -/- mutant.

first: Thiruvenkadam

last: Shanmugam

first: Enrico

last: Schleiff


title: Metabolic targeting as a strategy to overcome targeted therapy resistance in NRAS-mutated melanoma

city: Zurich

first: Zsolt

last: Balázs

address: Schmelzbergstrasse 26

institute: University of Zurich

summary: We used single cell RNA sequencing (scRNA-seq) to analyze the molecular response of melanoma xenografts to combined MEK-inhibitng and metabolic targeting therapy.

overall_design: Patient-derived melanoma cell cultures were injected into the flank of Balb-c/nude mice. The xenografts of the different treatment groups were analyzed using scRNAseq.

first: Ossia

last: Eichhoff

first: Mitchell

middle: P

last: Levesque


title: The MuSK-BMP pathway maintains myofiber size in slow muscle through regulation of Akt-mTOR signaling

city: Providence

first: Justin

last: Fallon

state: RI

address: 185 Meeting St

department: Neuroscience

institute: Brown University

summary: Myofiber size regulation is critical in health, disease, and aging. MuSK (muscle-specific kinase) is a BMP (bone morphogenetic protein) co-receptor that promotes and shapes BMP signaling that is expressed at all neuromuscular junctions and is also present extrasynaptically in the slow soleus muscle. To investigate the role of the MuSK-BMP pathway in vivo we generated mice lacking the BMP-binding MuSK Ig3 domain. These ∆Ig3-MuSK mice are viable and fertile with innervation levels comparable to wild type. In 3-month-old mice myofibers are smaller in the slow soleus, but not in the fast TA. Here we use bulk RNA-seq to perform transcriptomic analysis of slow and fast mouse muscle. RNAseq analysis revealed soleus-selective decreases in RNA metabolism and protein synthesis pathways as well as dysregulation of IGF1 pathway components. Moreover, Akt-mTOR signaling is reduced in soleus but not TA. We propose that the MuSK-BMP pathway acts extrasynaptically to maintain myofiber size in slow muscle by promoting protein synthetic pathways including the IGF1-Akt-mTOR signaling.  These results reveal a novel mechanism for regulating myofiber size in slow muscle and introduce the MuSK-BMP pathway as a target for promoting muscle growth and combatting atrophy.

overall_design: 3 month old male mice were used in the study to compare transcriptomic profiles of TA and soleus muscle. 9 WT and 9 ∆Ig3-MuSK tibialis anterior and soleus muscle (total of 36 samples) were used for bulk RNAseq analysis.

first: Diego

last: Jaime

first: Lauren

last: Fish

first: Laura

last: Madigan


title: Orthotopic CRC organoid transplantation in mice: A novel model for the study and treatment of peritoneal carcinomatosis [TIL scRNA-Seq]

city: Freiburg

first: Pierre

last: Cauchy

overall_design: scRNA-Seq from tumor-infiltrating lymphocytes (TIL) from organoid-derived primary tumor (PT), peritoneal carcinomatisis (PC) and liver metastasis (LM) CRC murine models

first: Christopher

last: Berlin

first: Lisa

last: Marx

first: Bernhard

last: Mauerer

last: Fichtner-Feigl

last: Miketiuk

first: Marina

last: Pesic

first: Florian

last: Greten

first: Claudia

last: Laessle

first: Jost

last: Lünstedt

first: Naomi

last: Rühl

first: Dominik

last: Jauch

first: Andreas

last: Jud

first: Philipp

last: Holzner

first: Esther

last: Biesel

first: Hannes

last: Neeff

first: Rebecca

last: Kesselring


title: Orthotopic CRC organoid transplantation in mice: A novel model for the study and treatment of peritoneal carcinomatosis

last: Cauchy

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

overall_design: Refer to individual Series


title: Metabolic fitness of IgA+ plasma cells in the gut requires DOCK8

city: Farmington

last: Yurieva

state: Connecticut

address: 10 Discovery dr

department: Computational Sciences

institute: Jackson Laboratory

summary: DOCK8 is required for T cell-dependent gut IgA by maintaining plasma cell metabolic fitness

overall_design: 16S of v4 region

first: Biyan

last: Zhang

first: Shuting

last: Chen

first: Xiangyun

last: Yin

first: Jake

last: Gertie

first: Agata

last: Bielecka

first: Brian

last: Hoffmann

first: Travis

last: Hinson

first: Jessica

last: Grassman

first: Lan

last: Xu

first: Emily

last: Siniscalco

first: Arielle

last: Soldatenko

last: Hoyt

first: Julie

last: Joseph

first: Elizabeth

middle: B

last: Norton

first: Gowthaman

last: Uthaman

first: Noah

middle: W

last: Palm

first: Elise

last: Liu

first: Adam

last: Williams

first: Stephanie

last: Eisenbarth


title: Long noncoding RNA lncMREF promotes myogenic differentiation and muscle regeneration by interacting with the Smarca5/p300 complex [RNA-seq]

city: wuhan

first: wei

last: jiang

address: No.1, Shizishan Street, Hongshan District, Wuhan, China

institute: Huazhong Agricultural University

summary: Here, we identified a novel lncRNA named lncMREF as a specific positive regulator of muscle regeneration in mice, pigs and humans. Functional studies demonstrated that lncMREF is significantly upregulated in activated skeletal muscle satellite cells and promotes myogenic differentiation and muscle regeneration. Mechanistically, lncMREF interacts with Smarca5 to promote chromatin remodeling and accessibility when muscle satellite cells are activated, thereby facilitating genomic binding of p300/H3K27 to upregulate the expression of myogenic regulators, such as MyoD and cell differentiation. Our results unravel a new temporal-specific epigenetic regulation during muscle regeneration and reveal that lncMREF/Smarca5-mediated epigenetic programming is responsible for muscle satellite cell differentiation, which provides new insights into the regulatory mechanism of muscle regeneration in adult animals.

overall_design: RNA-seq in skeletal muscle satellite cells differentiated for 2 days from WT mice and lncMREF KO mice

first: Wei

last: Lv

last: Jiang

first: Bo

last: Zuo


title: Long noncoding RNA lncMREF promotes myogenic differentiation and muscle regeneration by interacting with the Smarca5/p300 complex [ATAC-seq]

summary: Long noncoding RNAs play important roles in the spatial and temporal regulation of muscle development and regeneration. Nevertheless, the determination of their biological functions and mechanisms underlying muscle satellite cell differentiation remains challenging. Here, we identified a novel lncRNA named lncMREF as a specific positive regulator of muscle regeneration in mice, pigs and humans. Functional studies demonstrated that lncMREF is significantly upregulated in activated skeletal muscle satellite cells and promotes myogenic differentiation and muscle regeneration. Mechanistically, lncMREF interacts with Smarca5 to promote chromatin remodeling and accessibility when muscle satellite cells are activated, thereby facilitating genomic binding of p300/H3K27 to upregulate the expression of myogenic regulators, such as MyoD and cell differentiation. Our results unravel a new temporal-specific epigenetic regulation during muscle regeneration and reveal that lncMREF/Smarca5-mediated epigenetic programming is responsible for muscle satellite cell differentiation, which provides new insights into the regulatory mechanism of muscle regeneration in adult animals.

overall_design: ATAC-seq in skeletal muscle satellite cells differentiated for 2 days from WT mice and lncMREF KO mice


title: Long noncoding RNA lncMREF promotes myogenic differentiation and muscle regeneration by interacting with the Smarca5/p300 complex [ChIP-seq_H3k27ac]

overall_design: H3k27ac ChIP-seq in skeletal muscle satellite cells differentiated for 2 days from WT mice and lncMREF KO mice


title: Long noncoding RNA lncMREF promotes myogenic differentiation and muscle regeneration by interacting with the Smarca5/p300 complex


title: JOSD2 promotes non-small cell lung cancer proliferation by removing K6-linked polyubiquitination from LKB1

city: Hanhzhou

first: fujing

last: ge

address: No. 866 Yuhangtang Road

institute: Zhejiang University

summary: Deubiquitinating enzymes (DUBs), frequently overactivated in cancers, are associated with tumorigenesis and regarded as promising therapeutic targets. However, the tumor-promoting role and underlying mechanism of DUBs in non-small cell lung cancer (NSCLC) are poorly understood. Through a global analysis of the contribution of 88 DUBs in NSCLC survival possibilities, we found that high expression of Josephin Domain-containing protein 2 (JOSD2) predicted the poor prognosis of patients. Depletion of JOSD2 significantly impeded NSCLC tumor growth in vivo in both NCI-H1299-derived xenografts and patient-derived xenografts. Mechanistically, JOSD2 functioned as a DUB by removing K6-linked polyubiquitination from LKB1, which was critical for maintaining LKB1-STRAD-MO25 complex integrity and hence its kinase activity. Furthermore, for the first time, we identified small molecule inhibitor of JOSD2 and the pharmacological inhibition of JOSD2 significantly arrested NSCLC proliferation both in vitro and in vivo. Notably, our findings demonstrate a crucial role of JOSD2 in hindering LKB1 activity, highlighting JOSD2 as a potential therapeutic target in NSCLC and providing its inhibitors as a promising strategy for NSCLC treatment.

overall_design: mRNA profiles of  knocking down JOSD2 in H1299 cells

first: Tao

last: Yuan

first: Chenming

last: Zeng

first: Jiawei

first: Chenxi

last: Zhao

first: Fujing

last: Ge

first: Yuekang

last: Li

first: Meijia

last: Qian

first: Xiaoyang

last: Dai

first: Xueqin

last: Chen

first: Shenglin

last: Ma

first: Xiaowu

last: Dong

first: Hong

last: Zhu

first: Qiaojun

last: He

last: Yang


title: Gene expression data from a Brazilian cohort of pediatric medulloblastomas

city: Ribeirão Preto

first: Carlos

middle: Alberto

last: Scrideli

state: São Paulo

address: Avenida Bandeirantes 3900

department: Pediatrics

country: Brazil

institute: Ribeirao Preto Medicine School - University of Sao Paulo

summary: Herein, we aimed to analyze the gene expression profile of medulloblastoma samples from a Brazilian cohort of 17 pediatric patients.

overall_design: mRNA expression profiles of four Wnt, four Shh, four Group 3, and five Group 4 pediatric medulloblastoma samples using high throughput sequencing.

first: L

middle: G

last: Tone

first: C

first: E

last: Valera

last: Carlotti

first: R

last: Queiroz


title: Spatiotemporal heterogeneity of inflammatory changes in Alzheimer's disease analyzed spatially resolved transcriptome

city: Seoul

first: Eun Ji

last: Lee

address: 17dong-304 ho, Seoul national university hospital

department: Nuclear medicine

institute: Seoul National University

summary: We investigated spatiotemporal molecular patterns related to AD pathophsiology using spatially resolved transcriptome of the AD mouse model. The late change of gray matters of AD was commonly related to neuroinflammation, while the early change in the white matter of AD represented neuronal projection and ensheathment of axons before the amyloid plaques accumulation. Disease-associated microglia and astrocyte signatures were spatially differently enriched. Our results provide a key spatiotemporally heterogeneous molecular change particularly related to inflammation in AD.

overall_design: Distinctive brain regions were identified and molecular changes in AD model at early (3-month-old) and late (7-month-old) phases were analyzed.

first: Hongyoon

last: Choi


title: Extracellular proximity labeling reveals an expanded interactome for the matrisome protein TIMP2

status: Public on Jan 09 2024

city: bethesda

first: David

last: Peeney

state: MD

address: 10 Center Drive, Building 10, 6B05

institute: NCI

summary: Classical methods of investigating protein-protein interactions (PPIs) are generally performed in non-living systems, yet in recent years new technologies utilizing proximity labeling (PL) have given researchers the tools to explore proximal PPIs in living systems. PL has distinct advantages over traditional protein interactome studies, such as the ability to identify weak and transient interactions in vitro and in vivo. Most PL studies are performed on targets within or on the cell membrane. We have adapted the original PL method to investigate PPIs within the extracellular compartment, using both BioID2 and TurboID, that we term extracellular PL (ePL). To demonstrate the utility of this modified technique, we investigate the interactome of the widely expressed matrisome protein Tissue inhibitors of metalloproteinases 2 (TIMP2). Tissue inhibitors of metalloproteinases (TIMPs) are a family of multi-functional proteins that were initially defined by their ability to inhibit the enzymatic activity of metalloproteinases (MPs), the major mediators of extracellular matrix (ECM) breakdown and turnover. TIMP2 exhibits a broad expression profile and is often abundant in both normal and diseased tissues. Understanding the functional transformation of matrisome regulators, like TIMP2, during the evolution of tissue microenvironments associated with disease progression is essential for the development of ECM targeted therapeutics. Using carboxyl- and amino-terminal fusion proteins of TIMP2 with BioID2 and TurboID, we describe the TIMP2 proximal interactome. We also illustrate how the TIMP2 interactome changes in the presence of different stimuli, in different cell types, in unique culture conditions (2D vs 3D), and with different reaction kinetics (BioID2 vs. TurboID); demonstrating the power of this technique versus classical PPI methods. We propose that the screening of matrisome targets in disease models using ePL will reveal new therapeutic targets for further comprehensive studies.

overall_design: To assess the effects of phorbol 12-myristate 13-acetate (PMA; 40nM) or Concanavalin A (ConA; 40ug/mL) treatment in HT1080 cells

first: William

last: Stetler-Stevenson


title: Tumor associated macrophages-programmed core immunosuppressive microenvironments via Galectin-1 in breast cancer

state: Seoul Teugbyeolsi

address: Daehakro 101, Jongrogu

institute: Seoul National University Hospital

summary: There has been considerable interest in therapeutic targeting of tumor-associated macrophages (TAMs) mainly by depleting or repolarizing them toward anti-tumoral phenotypes. However, a core mediator co-opted for TAMs-mediated remodeling of tumor microenvironment remains poorly understood. Here, to dissect TAMs-mediated early microenvironment, we performed single-cell RNA sequencing of TAMs-enriched and -depleted mouse breast tumor at the early stages of progression, before detectable change in tumor growth appeared.  We found that early intratumoral accumulation of TAMs endowed cancer cells with invasive properties to promote early dissemination and dampened antitumoral T cell responses. Accordingly, TAMs-depleted tumor using clodronate displayed a decreased epithelial-to mesenchymal transition (EMT) signature of cancer cells and harbored a distinct transcriptome associated with CD8+ T cells activation. Furthermore, we identified a role of Galectin-1 (Gal-1) as a molecular checkpoint in TAMs-induced CD8+ T cell exhaustion. Gal-1 inhibition reversed immune suppression via reinvigoration of CD8+ T cells, thus impairing tumor growth and boosting the efficacy of immune checkpoint inhibitor in a breast tumor model. These results provide a comprehensive insight into the early-programmed microenvironment by TAMs and reveal an immune evasion mechanism that could be targeted by Gal-1 to unleash antitumor immune responses.

overall_design: To establish orthotopic implantation model, 4T1-Luc2 cells were orthotopically implanted into the fourth mammary fat pad of 8-week-old female BALB/c mice. Depletion of macrophages was performed by intraperitoneal injection of clodronate or vehicle liposome (Encapsula Nano Science) at days 3, 5 and 7 after 4T1 implantation. The cell suspensions were diluted in nuclease-free water to achieve a targeted cell count of 10,000. Cell suspension was mixed with master mix and loaded with Single Cell 3’V3.1 Gel Beads and Partitioning Oil into a chromium Next GEM chip G. RNA transcripts from single cells were uniquely barcoded and reverse-transcribed within droplets.

first: Hyewon

last: Chung

first: YiRang

first: YunSang

first: SeungHyeok

last: Seok


title: Activation of quiescent neurogenic niches of aging brain

city: La Jolla

first: Colin

last: Kern

state: CA

address: 9500 Gilman Dr

institute: UC San Diego

summary: Proposals for induced glia-to-neuron conversion have raised the potential for generating new neurons to replace those lost due to injury, aging or neurodegenerative diseases. Here, single-cell spatial transcriptomics [Multiplexed Error Robust Fluorescence In Situ Hybridization (MERFISH)] is used to construct a spatial cell atlas of the subventricular and dentate gyrus neurogenic niches of young and aged adult murine brain. RNAs that encode the RNA binding protein Polypyrimidine Tract-Binding Protein (PTBP1) in the aged murine brain are determined to be highest in glia that line previously active neurogenic niches. A glial cell population with ependymal character within an initially quiescent subventricular neurogenic niche in the aged murine brain is identified that upon transient suppression of PTBP1 reenters the cell cycle, replicates DNA, and converts into neurons through a canonical adult neurogenesis pathway. Glia-derived neurons migrate from this niche, with some neurons transiting to the striatum and acquiring a transcriptome characteristic of GABAergic inhibitory neurons. Similar PTBP1 expressing quiescent glia are identified in the corresponding neurogenic niche of aged human brain. Thus, transient reduction of PTBP1 holds potential for inducing the generation of new neurons in quiescent neurogenic niches of the aged nervous system, thereby offering promising therapeutic applications.

overall_design: Hippocampus from 3 adult wildtype mice were dissected and sequenced with scRNA-seq


title: The Tumor Microenvironment of Laryngeal Squamous Cell Carcinoma Revealed by Single-Cell Transcriptomics [II]

city: shenyang

first: sun

middle: yuan

last: yuan

address: 沈北新区蒲河路77号

institute: China Medical University

summary: Laryngeal squamous cell carcinoma (LSCC) is a malignant tumor with a high possibility of metastasis. The tumor microenvironment (TME) is well known to play an important role in LSCC metastasis. To gain insights into the TME of LSCC, we performed single-cell RNA-seq (scRNA-seq) using LSCC with lymph node metastases.

overall_design: We collected 3 fresh laryngeal cancer tissues from 3 patients immediately after surgery. Single-cell suspension was prepared immediately and then subjected to 3’ droplet- based single-cell sequencing (10×Genomics)

first: Yuanyuan

last: Sun

first: Weineng

last: Fu

first: Wei

last: Yan

first: Zhenming

last: Xu

first: Sheng

last: Chen

first: Yongping

last: Lu


title: Hippocampus and cortex of mice exposed to urban particulate matter

first: Bu-Yeo

last: Kim

address: 1672 Yuseongdae-ro, Yuseong-gu

department: Herbal Medicine Research Division

institute: Korea Institute of Oriental Medicine

summary: Urban particulate matter (UPM) is known to be a risk factor for respiratory and cardiovascular diseases, but recent studies report that UPM exposure is associated with the development of brain disorders. In this study, we performed bioinformatic analysis to elucidate the molecular mechanisms of the effects of UPM exposure on the brain.

overall_design: UPM SRM 1648a was purchased from Sigma-Aldrich (St. Louis, MO, USA) and certified by the National Institute of Standards and Technology (NIST) (Gaithersburg, MD , USA). Dispersed suspensions of SRM1648a UPM were prepared by sonication in sterile PBS for 15 min in a cooling water bath. Seven-week-old male C57BL/6 mice were exposed intranasally to PBS (vehicle) or UPM once daily for 3, 5, and 7 days (short-term exposure) and twice per week for 3, 8, 12, 16, and 20 weeks (long-term exposure). Total RNA was extracted from hippocampus and cortex of mice and then used for sequencing for QuantSeq Analysis.

first: Soo-Jin

last: Jeong


title: Long noncoding RNA lncMREF promotes myogenic differentiation and muscle regeneration by interacting with the Smarca5/p300 complex [ChIP-seq_p300]

first: wei

last: jiang

overall_design: p300 ChIP-seq in skeletal muscle satellite cells differentiated for 2 days from WT mice and lncMREF KO mice

last: Lv

last: Jiang

first: Bo

last: Zuo


title: Histone demethylase UTX regulates differentiation, mineralization, and homeostasis in osteoblast and osteoclast interation

city: Kaohsiung

middle: Shiung

last: Lian

address: No.123, Dapi Rd., Niaosong Dist.,

department: Department of Medic al Research

institute: Kaohsiung Chang Gung Memorial Hospital

summary: This study is the first indicated that osteoblast-specific UTX deficiency adverse to bone tissue integrity and increase osteoporosis development.

overall_design: Mouse osteoblast transcripotomic analysis in wt and Col1a1-UTX-KO mice.

first: Yu-Shan

first: Wei-Shiung

first: Feng-Sheng

last: Wang