title: Single-cell RNA-sequencing of porcine submandibular lymph node cells from ASF-immune and nonimmune pigs

first: Jordi

last: Argilaguet

summary: We describe the recall response to African swine fever virus (ASFV) by applying single-cell RNA-sequencing (scRNA-seq) of submandibular lymph node (LN) cells from a control and a vaccinated animal with the live attenuated BA71ΔCD2 vaccine prototype. Cell suspensions obtained from the digested tissues were in vitro stimulated for 16 hours with BA71ΔCD2 ASFV, and methanol-fixed prior sequencing using the 10x Genomics scRNA-seq platform. We identified 22 transcriptionally distinctive clusters which were assigned to different cell subsets based on canonical lineage markers. Interferon-stimulated genes (ISG) were significantly upregulated in several cell subsets from the vaccinated pig when compared to the control one. Several populations were overrepresented in LN cells from the vaccinated pig, suggesting their contribution to the ASFV-specific recall response. These included several B cell subsets such as plasmablasts and plasma cells, an undefined CD4 T cell subset, and γδ T cells. The proinflammatory CXCL10 chemokine was strongly upregulated in plasmablasts, in the undefined CD4 T cell subset, and in crosspresenting DCs, thus showing the induction of a Th1-biased recall response. Of particular interest was the presence of a robust vaccine-specific cytotoxic response characterized by elevated numbers of responding CD8 T cells. Indeed, these subset significantly upregulated GZMA.1, confirming their activated status, while it was similarly expressed in NK cells from both samples. Overall, scRNA-seq allowed deciphering the complex protective immune response against ASFV infection, demonstrating a major role of an early Th1-mediated inflammatory response concomitant with a rapid expansion of cytotoxic CD8 T cells.

overall_design: 10x Genomics single-cell RNA-sequencing (scRNA-seq) of submandibular LN cells from a control and a BA71ΔCD2-vaccinated animal after in vitro stimulation for 16 hours with BA71ΔCD2 ASFV and methanol fixation.

first: Anna

last: Esteve-Codina

first: Beatriz

last: Martín-Mur

first: Marc

last: Dabad

first: Laia

last: Bosch-Camós

first: Uxía

last: Alonso

first: Boris

last: Gavrilov

first: Fernando

last: Rodríguez


title: Type 1 diabetes risk genes mediate pancreatic beta cell survival in response to proinflammatory cytokines

status: Public on Oct 31 2022

city: La Jolla

first: Paola

last: Benaglio

state: CA

address: 9500 Gilman Drive #0761

department: Pediatrics

country: USA

institute: University of California San Diego

type: Genome binding/occupancy profiling by high throughput sequencing

type: Expression profiling by high throughput sequencing

summary: Beta cells intrinsically contribute to the pathogenesis of type 1 diabetes (T1D), but the genes and molecular processes that mediate beta cell survival in T1D remain largely unknown. We combined high throughput functional genomics and human genetics to identify T1D risk loci regulating genes affecting beta cell survival in response to the proinflammatory cytokines IL-1b, IFNg, and TNFa. We mapped cytokine-responsive candidate cis-regulatory elements (cCREs) active in beta cells using ATAC-seq and single nuclear ATAC-seq (snATAC-seq), and linked cytokine-responsive beta cell cCREs to putative target genes using single cell co-accessibility and HiChIP. We performed a genome-wide pooled CRISPR loss-of-function screen in EndoC-βH1 cells, which identified hundreds of genes affecting cytokine-induced beta cell loss. We identified thousands of variants in cytokine-responsive beta cell cCREs altering transcription factor (TF) binding using high-throughput SNP-SELEX. Together our findings reveal processes and genes acting in beta cells during cytokine exposure that intrinsically modulate risk of T1D.

overall_design: Primary human islets from 12 donors were cultured in vitro with pro-inflammatory cytokines (IL-1b, IFNg, and TNFa) at multiple doses and durations. ATAC-seq, snATAC-Seq (10x Genomics) and RNA-seq were performed in treated and untreated matched samples to map islet and beta cells regulatory programs in response to cytokine stimulation. The cell line EndoC-βH1, a model for human beta cells, was profiled with HiChIP in untreated and cytokine-treated conditions, to identify long range chromatin interaction, and was used to perform a CRIPSR-KO screen to identify genes affecting cytokine-induced beta cell loss. SELEX-Seq was used to determine the in-vitro binding of hundreds of transcription factors at genetic variants located within islet regulatory elements.

first: Han

last: Zhu

first: Mei-Lin

last: Okino

first: Jian

last: Yan

first: Ruth

last: Elgamal

first: Naoki

last: Nariai

first: Elisha

last: Beebe

first: Katha

last: Korgaonka

first: Yunjiang

last: Qiu

first: Margaret

last: Donovan

first: Joshua

last: Chiou

first: Gaowei

last: Wang

first: Jacklyn

last: Newsome

first: Jaspreet

last: Kaur

first: Sierra

last: Corban

first: Anthony

last: Aylward

first: Jussi

last: Taipale

first: Bing

last: Ren

first: Kelly

middle: A

last: Frazer

first: Maike

last: Sander

first: Kyle

middle: J

last: Gaulton


title: Phase separation of YAP fusion proteins drives supratentorial ependymoma I

status: Public on Oct 27 2022

city: Cincinnati

first: Richard

last: Lu

state: OH

address: 3333 BURNET AVENUE

department: Brain Tumor Center

institute: Cincinnati Children's Hospital Medical Center

summary: HIPPO-YAP/TAZ signaling has been implicated in supratentorial ependymoma formation from neural progenitor cells (NPC) in the brain, however, the underlying mechanisms  to trigger the neural progenitor cell transformation remains elusive. Here, we uncover that patient-derived tumorigenic YAP-fusion proteins (YAP-MAMLD1 and C11ORF95-YAP) promote ependymoma tumorigenesis through forming liquid-liquid phase-separated condensates. Intrinsically disordered regions (IDR) in the fusion proteins promote oligomerization of YAP-transcriptional co-activators and self-assembly of nuclear puncta-like membrane-less organelles. Phase separation of YAP-fusion proteins further facilitates the compartmentalization of transcriptional coactivators, BRD4 and MED1, resulting in pervasive enhancer landscape changes and exclusion of transcriptional repressors such as PRC2 complexes. YAP-fusion proteins-induced nuclear puncta recruit RNA polymerase II to promote transcriptional bursting of multiple oncogenic pathways. Moreover, we show that IDR-mediated phase separation is necessary for YAP-fusion protein-induced tumor formation. Distinct YAP fusion-proteins identified in other human tumors also encompass IDR features. Together, our data suggest that IDR-mediated phase separation is an integral component of YAP-fusion protein-induced tumorigenesis and might serve as a therapeutic target in supratentorial ependymoma.

overall_design: RNA-seq and ChIP-seq

first: Xiaohua

last: Hu


title: Comparative transcriptomic and proteomic analysis reveals common molecular factors responsive to heat and drought stress in sweetpotato (Ipomoea batatas)

status: Public on Oct 23 2022

city: Xuzhou

first: Wei

last: Tang

address: Kunpeng Road num 78

country: China

institute: Xuzhou Institute of Agricultural Sciences in Jiangsu Xuhuai District

summary: In the process of field production, crops are often affected by a variety of abiotic stresses, among which heat (HT) and drought (DR) stress are the most common co-stresses in summer. Although a large number of studies have been carried out on HT and DR stress respectively, little is known about how their combination (DH) affects plants. In this study, we investigated the responses of sweetpotato to HT, DR or DH stress by RNA-seq and DIA technologies, and set up a controlled experiment and quantified gene expression and protein concentrations from paired samples. A total of 12 cDNA libraries were constructed under HT, DR, DH and control condition. We identified 536, 389 and 907 DEGs in response to HT, DR or DH stress, of which 147 were shared and 447 were specifically identified under DH stress. Proteomic analysis identified 1609, 1168 and 1535 DEPs under HT, DR and DH treatments compared to the control, of which 656 were shared and 358 were exclusively identified under DH stress. Further analysis revealed that some DEGs/DEPs associated with heat shock protein, carbon metabolism, phenylalanine metabolism, starch and cellulose metabolism, plant defense and so on. Correlation analysis identified a number of co-expressed genes and proteins under HT, DR or DH stress. Meanwhile, a cross-comparison of transcriptomics and proteomics data identified 59, 35 and 86 significant co DEGs and DEPs genes under HT, DR and DH stress respectively. This is the first time that studies the differential genes and proteins of sweet potato under DH stress, and hopes that the results of this study will help us to understand the molecular mechanism of sweet potato resistance to heat and drought stress.

overall_design: RNA samples from leaves and tuberous roots at each time point under heat, drought and their co-stress respectively as a mixing pool to construct four sequencing libraries, named as HT (heat), DR (drought), DH (drought and heat) and CK (control)

first: Mohamed

middle: H

last: Arisha


title: RNA-seq using human SH-SY5Y neuroblastoma cells used for SILAC experiment

status: Public on Oct 30 2022

city: Rochester

first: Tatsuaki

last: Kurosaki

state: NY

address: 601 Elmwood Avenue, Box 712

department: Biochemistry and Biophysics

institute: University of Rochester

summary: To measure translational efficiency in FMRP depletion, we purified RNAs from either wild-type or FMR1-knockout (FMR1-KO) SH-SY5Y cells generated for SILAC coupled to LC-MS/MS analysis and performed RNA-seq to quantitate mRNA abundance to normalize their protein abundance.

overall_design: RNA profiles of wild-type (n=6) and FMR1-knockout SH-SY5Y cells (n=6) culturing in either SILAC heavy (containing 13C6,15N4 L-arginine and 13C6,15N2 L-lysine) or light (containing 12C6,14N4 L-arginine and 12C6 L-lysine) medium.

first: Lynne

middle: E

last: Maquat


title: Phase separation of YAP fusion proteins drives supratentorial ependymoma (methyl-seq)

type: Methylation profiling by high throughput sequencing

overall_design: methyl-Seq, 6 samples


title: HDAC1 regulates the chromatin landscape to control transcriptional dependencies in chronic lymphocytic leukemia [RNA-seq]

status: Public on Oct 25 2022

city: Columbus

first: Ayse

middle: Selen

last: Yilmaz

address: 1800 Cannon Drive

department: Biomedical Informatics

institute: OSU

summary: Chronic lymphocytic leukemia (CLL) is a quiescent B-cell malignancy that depends on transcriptional dysregulation for survival.  The histone deacetylases are transcriptional regulators whose role within the regulatory chromatin and consequence on the CLL transcriptome is poorly characterized.  Here, we profiled and integrated the genome wide occupancy of HDAC1, BRD4, H3K27Ac and H3K9Ac signals with chromatin accessibility, Pol2 occupancy and target expression signatures in CLL cells. We identified that when HDAC1 was recruited within super-enhancers (SEs) marked by acetylated H3K27 and BRD4, it functioned as a transcriptional activator that drove the de novo expression of select genes to facilitate survival and progression in CLL. Targeting HDACs reduced BRD4 and Pol2 engagement to downregulate the transcript and proteins levels of specific oncogenic driver genes in CLL such as BLK, a key mediator of the B-cell receptor pathway, core transcription factors such as PAX5 and IKZF3 and the anti-apoptotic gene, BCL2. Concurrently, HDAC1, when recruited in the absence of super-enhancers repressed target gene expression. HDAC inhibition reversed silencing of a defined set of protein coding and noncoding RNA genes. We focused on a specific set of microRNA genes and show that their upregulation was inversely correlated with the expression of CLL specific survival, transcription factor and signaling genes. Our findings identify that the transcriptional activator and repressor functions of HDACs cooperate within the same tumor to establish the transcriptional dependencies essential for survival in CLL.

overall_design: CLL samples (untreated or exposed to 400mM abexinostat) were harvested after 24h of drug exposure, extracted for total RNA and libraries prepared and seqeuenced by total RNA Seq

middle: S

first: Hatice

middle: G

last: Ozer

first: Deepa

last: Sampath

first: Tzung-Huei

last: Lai


title: HDAC1 regulates the chromatin landscape to control transcriptional dependencies in chronic lymphocytic leukemia [ChIP-seq]

overall_design: CLL Cells were treated with vehicle (DMSO) or with abexinostat (0.4 mM) for 6 h before being harvested and processed for chromatin innunoprecipitation (ChIP) with the HDAC1, BRD4, H3K9Ac, H3K27Ac and RNA Pol II antibodies.


title: Transcriptome sequencing of Xenopus laevis animal caps at six time points in transit from pluripotency to 4 lineages: epidermal, neural, ventral mesoderm and endoderm

city: Evanston

first: Carole

last: LaBonne

state: IL

address: 2205 Tech Dr

department: Molecular Biosciences

institute: Northwestern University

summary: The purpose of this study is to examine transciptome dynamics at high resolution to 4 separate lineages. Here we provide snapshots of the Xenopus laevis transcriptome at Nieuwkoop and Faber stages 9., 10, 10.5, 11, 12 and 13 for the epidmeral, neural, ventral mesoderm and endoderm lineage

overall_design: Methods: mRNA profiles of Xenops animal cap populations at st9, 10, 10.5, 11, 12 13 in transit to the following lineages: epidermal (untreated), neural (100ng/uL noggin), ventral mesoderm (20ng/uL BMP4/7), endoderm (160ng/uL activin) were generated by Next Gen Sequencing

first: Kristin

last: Johnson


title: Genome-wide maps of H3K27me3 states in Arabidopsis thaliana flowers.

city: Harbin

first: Ralf

last: Mueller-Xing

address: NO.26 Hexing Road

institute: Northeast Forestry University

summary: Arabidopsis AP1-GR ap1-1 cal-1 were grown under long-day (16 h light/8 h dark) condition. After bolding (26 DAG), half of the plants were treated with dexamethasone. 31 DAG, the untreated inflorescenes were sampled as t0 and the dexamethasone treated one as t5.

overall_design: Examination of global H3K27me3 levels at 2 different flower stages in AP1-GR inflorescences.


title: Levofloxacin induces the downexpression of inflammation-related transcriptome in the gut of spondyloarthritis DBA/1 mice.

status: Public on Oct 22 2022

city: Chihuahua

first: Susana

middle: Aideé

last: González-Chávez

state: Chihuahua

address: Circuito Universitario Campus II

department: Facultad de Medicina

country: Mexico

institute: Universidad Autónoma de Chihuahua

summary: Gene expression profiles in the gut of DBA/1 mice whit spontaneus arthritis and treated with levofloxacion vs. those who were not received levofloxacin were compared. Levofloxacin induced the downexpression of inflammation-related genes and signaling pathways.

overall_design: Pools of total RNA were made per study group (six mouse per group): DBA1.SpA.Levo mice (test group) and DBA1.SpA.control mice (reference). The reverse transcription polymerase chain reaction (RT-PCR) was performed and the resulting complementary DNAs were labeled with Cy5 (DBA1.SpA.Levo) or Cy3 (DBA1.SpA.control). Hybridation analysis used the mouse 65-mer oligo library from Sigma-Genosys to compare the expression of 23,232 gene-specific oligonucleotide probes for mouse.

first: César

last: Pacheco-Tena


title: Levofloxacin induces the downexpression of inflammation-related transcriptome in the tarsal joint of Spondyloarthritis DBA/1 mice.

summary: Gene expression profiles in the tarsal joints of DBA/1 mice whit spontaneus arthritis and treated with levofloxacion vs. those who were not received levofloxacin were compared. Levofloxacin induced the downexpression of inflammation-related genes and signaling pathways.


title: Levofloxacin induces the downexpression of inflammation-related transcriptome in the spine of spondyloarthritis DBA/1 mice.

summary: Gene expression profiles in the spine of DBA/1 mice whit spontaneus arthritis and treated with levofloxacion vs. those who were not received levofloxacin were compared. Levofloxacin induced the downexpression of inflammation-related genes and signaling pathways.


title: Microglia influence host defense, disease, and repair following coronavirus infection of the central nervous system

status: Public on Oct 21 2022

city: Salt Lake City

first: Amber

last: Syage

state: Utah

address: 2000 Circle of Hope

department: Pathology

institute: University of Utah

summary: The present study examines functional contributions of microglia in host defense, demyelination, and remyelination following infection of susceptible mice with a neurotropic coronavirus. Treatment with PLX5622, an inhibitor of colony stimulating factor 1 receptor (CSF1R) that efficiently depletes microglia, prior to infection of the central nervous system (CNS) with the neurotropic JHM strain of mouse hepatitis virus (JHMV) resulted in increased mortality compared with control mice that correlated with impaired control of viral replication. Single cell RNA sequencing (scRNASeq) of CD45+ cells isolated from the CNS revealed that PLX5622 treatment resulted in muted CD4+ T cell activation profile that was associated with decreased expression of transcripts encoding MHC class II and CD86 in macrophages but not dendritic cells. Evaluation of spinal cord demyelination revealed a marked increase in white matter damage in PLX5622‐treated mice that corresponded with elevated expression of transcripts encoding disease‐associated proteins Osteopontin (Spp1), Apolipoprotein E (Apoe), and Triggering receptor expressed on myeloid cells 2 (Trem2) that were enriched within macrophages. In addition, PLX5622 treatment dampened expression of Cystatin F (Cst7), Insulin growth factor 1 (Igf1), and lipoprotein lipase (Lpl) within macrophage populations which have been implicated in promoting repair of damaged nerve tissue and this was associated with impaired remyelination. Collectively, these findings argue that microglia tailor the CNS microenvironment to enhance control of coronavirus replication as well as dampen the severity of demyelination and influence repair.

overall_design: Mice fed with either PLX5622 diet or control chow were injected intracranially (i.c.) in the right brain hemisphere with 250 plaque forming units (PFU) of JHMV and CD45-positive (CD45+) cells were flow sorted from the brains at day 7 post-infection (p.i.) and spinal cords at day 14 p.i. of JHMV-infected mice. FACS sorted CD45+ cells then underwent single-cell RNA-sequencing analysis

first: Vrushali

last: Mangale

middle: R

first: H

last: Ekiz

first: Dominic

middle: D

last: Skinner

first: Yuting

last: Cheng

first: Colleen

last: Stone

first: R

middle: M

last: Brown

first: Ryan

last: O'Connell

first: Kim

middle: N

last: Green

first: Thomas

last: Lane


title: Hepatic BCL6 and plasma trigylecrides regulate sexual dimorphism in tissue tolerance [set6_GDX]

city: San Francisco

first: Joni

last: Nikkanen

address: 555 Mission Bay Blvd S

institute: UCSF

summary: Aim of the experiment was to study the role of gonadectomy and testosterone treatment on liver gene expression of male mice. Gonadectomized male mice received infusion of testosterone or vehicle, and liver was used to perform RNAseq analysis.

overall_design: 4-week-old WT C57BL/6J male mice were gonadectomized and received a continuous infusion of testosterone or vehicle for 2 weeks starting at 8 weeks of age.

first: Yew

last: Leong

first: William

last: Krause

first: Ajay

last: Chawla


title: Hepatic BCL6 and plasma triglycerides regulate sexual dimorphism in tissue tolerance [set 2]

summary: Hepatic gene expression shows sexual dimorphism. Here, we investigated the role of BCL6 in establishing sexual dimorphism in hepatic gene expression and created Bcl6Flox/Flox,Alb-Cre mice and performed RNAseq from livers of 4- and 8-week-old male and female Ctrl and BCL6 liver knock-out mice.

overall_design: Examination of liver transcriptome of Bcl6Flox/Flox and Bcl6Flox/Flox,Alb-Cre male and female mice.


title: An evolutionary trade-off between host immunity and metabolism drives fatty liver in male mice.

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

overall_design: Refer to individual Series


title: Hepatic BCL6 and plasma triglycerides regulate sexual dimorphism in tissue tolerance [set 3]

summary: Here, we investigated the role of BCL6 in hepatic response to E.Coli infection. Bcl6 F/F and Bcl6 F/F, Alb-Cre male and female mice were infected with E.Coli and livers were collected 24h after infection for RNAseq analysis.

overall_design: Examination of liver transcriptome of Bcl6Flox/Flox and Bcl6Flox/Flox,Alb-Cre male and female mice infected with E.Coli.


title: Expression profiling analysis reveals key microRNA-mRNA interactions in patients with transposition of the great arteries and systemic left and right ventricles

status: Public on Oct 20 2022

city: Homburg

first: Masood

last: Abu-Halima

address: kirrberger st

department: Human genetics

country: Germany

institute: Saarland University

type:
Expression profiling by array
Non-coding RNA profiling by array


title: Expression profiling analysis reveals key microRNA–mRNA interactions in patients with transposition of the great arteries and systemic left and right ventricles [mRNA]

summary:
RNA was purified from Paxgene blood collected samples
miRNA and mRNA microarrays were conducted to determine the genome-wide expression profiles in the blood of 16 TGA-RV patients, 16 TGA-LV patients, and 16 age and gender-matched controls

overall_design: RNA was purified using the PAXgene Blood RNA Kit

first: A

last: Meese

first: Hashim

last: Abdul-Khaliq


title: A computational workflow for the analysis of 3’ Tag-Seq data

status: Public on Oct 13 2022

city: Merced

first: Clarissa

middle: Jane

last: Nobile

address: 5200 North Lake Rd

department: Molecular and Cell Biology

institute: University of California, Merced

summary: RNA-sequencing (RNA-seq) is a ubiquitous tool to profile genome-wide changes in gene expression. RNA-seq uses high-throughput sequencing technology to quantify the amount of RNA in a biological sample. With the increasing popularity of RNA-seq, many variations on the protocol have been proposed to extract unique and relevant information from biological samples. 3’ Tag-Seq (also called TagSeq, 3′ Tag-RNA-Seq, and Quant-Seq 3′ mRNA-Seq) is one RNA-seq variation, where the 3’ end of the transcript is selected and amplified to yield one copy of cDNA from each transcript in the biological sample.We present a simple, easy to use, and publicly available computational workflow to analyze 3’ Tag-Seq data. The workflow begins by trimming sequence adapters from raw FASTQ files. The trimmed sequence reads are checked for quality using FastQC, aligned to the reference genome, and read counts are obtained using STAR. Differential gene expression analysis is performed using DESeq2, based on differential analysis of gene count data. The outputs of this workflow are MA plots, tables of differentially expressed genes, and UpSet plots.This protocol is intended for users specifically interested in analyzing 3’ Tag-Seq data. As such, transcript length-based normalizations are not performed within the workflow. Future updates to this workflow could include custom analyses based on the gene counts table as well as data visualization enhancements.

overall_design: Comparative gene expression profiling of Candida albicans transcription factor TF028 mutant samples with wildtype samples.

first: Priyanka

last: Bapat


title: ACKR3 promotes CXCL12/CXCR4-mediated migration of lymphoma cells

city: Bellinzona

first: Mathilde

last: Foglierini

address: Via Vincenzo Vela 6

country: Switzerland

institute: Institute for Research in Biomedicine

summary: Chemotaxis is an essential physiological process, often harnessed by tumors for metastasis. CXCR4, its ligand CXCL12 and the atypical receptor ACKR3 are overexpressed in many human cancers. Interfering with this axis by ACKR3 deletion impairs lymphoma cell migration towards CXCL12. Here, we propose a model of how ACKR3 controls the migration of the diffused large B-cell lymphoma VAL cells in vitro and in vivo in response to CXCL12. VAL cells expressing full-length ACKR3, but not a truncated version missing the C-terminus, can support the migration of VAL cells lacking ACKR3 (VAL-ko) when allowed to migrate together. This migration of VAL-ko cells is pertussis toxin-sensitive suggesting the involvement of a Gi-protein coupled receptor. RNAseq analysis indicate the expression of chemotaxis-mediating LTB4 receptors in VAL cells. We found that LTB4 acts synergistically with CXCL12 in stimulating the migration of VAL cells. Pharmacologic or genetic inhibition of BLT1R markedly reduces chemotaxis towards CXCL12 suggesting that LTB4 enhances in a contact-independent manner the migration of lymphoma cells. The results unveil a novel mechanism of cell-to-cell-induced migration of lymphoma.

overall_design: As control groups, ACKR3 WT VAL and ACKR3 KO VAL were considerated. Transcriptome of the control groups were compared with IgM+ ACKR3+ and IgM- ACKR3- cells, IgM KO cells and CXCL12 and CXCL11_12 stimulated cells. In total there are 14 samples with 5 biological replicates each.

first: Paola

last: Antonello

first: Diego

middle: U

last: Pizzagalli

first: Serena

last: Melgrati

first: Egle

last: Radice

first: Sylvia

last: Thelen

first: Marcus


title: Annexin A1 exerts renoprotective effects in experimental crescentic glomerulonephritis

status: Public on Oct 04 2022

city: Berlin

first: Robert

last: Labes

address: Charitéplatz 1

department: Institute of Translational Physiology

institute: Charité - Universitätsmedizin Berlin

summary: The glucocorticoid-inducible protein annexin A1 has been shown to function as key-regulator of the resolution phase of inflammation but its role in immune-mediated crescentic glomerulonephritis has not been studied so far. Acute crescentic glomerulonephritis was induced in annexin A1 deficient and wildtype mice using a sheep serum against rat glomerular basement membrane constituents. Alterations in gene expression were determined by RNA-Seq and gene ontology analysis. Intrinsic annexin A1 has a protective effect in reducing pro-inflammatory signals and infiltration of neutrophil granulocytes during crescentic GN. The annexin A1 signaling cascade may therefore provide novel targets for the treatment of inflammatory kidney disease.

overall_design: Comparative gene expression profiling analysis of RNA-seq data for kidney homogenates from nephritic wildtype and AnxA1 knockout mice.

first: Alexander

last: Paliege

first: Ralf

last: Mrowka


title: ULK3 is a key determinant of the keratinocyte self-renewal and tumorigenesis [shULK3 SCC13]

status: Public on Oct 10 2022

city: Charlestown

first: Sandro

last: Goruppi

state: Massachusetts

address: 13th Street

department: CBRC

institute: MGH-Partners Healthcare

summary: Transcriptomic profiling of human squamous cell carcinoma cells SCC13 infected with three ULK3 silencing lentivirus versus control virus

overall_design: Transcriptomic profiling of human squamous cell carcinoma cells SCC13 separately infected with three ULK3 silencing lentivirus versus control virus

first: Goruppi

last: Sandro

first: Andrea

last: Clocchiatti

first: Giulia

last: Bottoni

first: Min

last: Ma

first: Beatrice

last: Tassone

first: Paolo

last: Dotto


title: ULK3 is a key determinant of the keratinocyte self-renewal and tumorigenesis [shULK3 HKCs]

summary: Transcriptomic profiling of three strains of primary human keratinocytes infected with two ULK3 silencing lentivirus versus control virus

overall_design: Transcriptomic profiling of primary human keratinocytes  infected with two different ULK3 silencing lentivirus versus control virus


title: Upregulated PD-1 Signaling Is an Important Antagonist to Glomerular Health in Aged Mouse Kidneys

status: Public on Oct 01 2022

city: Box

first: Stuart

last: Shankland

state: WA

address: 1959 NE Pacific Avenue

department: Nephrology

institute: University of Washington, Seattle

summary: Kidney aging and its contribution to disease and its underlying mechanisms are not well understood. Yet with an aging population, kidney health becomes an important medical and socioeconomic factor. We previously showed that podocytes isolated from aged mice exhibit increased expression of Programed Cell Death Protein 1 (PD-1) surface receptor and its two ligands (PD-L1, PD-L2). We now extend this observation to aged human kidneys. In vitro studies in cultured podocytes demonstrate a critical role of PD-1 signaling in cell survival and the induction of a Senescence-Associated Secretory Phenotype (SASP). To prove that the PD-1 signaling is critical to podocyte aging, aged mice were injected with an anti-PD-1 antibody (aPD-1ab). This treatment significantly improved the aging phenotype of the kidney and liver. In the glomerulus, it increased the lifespan of podocytes, but not parietal epithelial, mesangial or endothelial cells. Moreover, transcriptomic and immunohistochemistry studies demonstrate that anti-PD-1 treatment also improved the health-span of podocytes. It restored the expression of canonical podocyte genes, transcription factors and gene regulatory networks, increased the cellular metabolism signatures and lessened the SASP of aged podocytes. Increased PD-1 transcripts in human glomeruli significantly correlated with reduced eGFR.Together, these results suggest a critical contribution of increased PD-1 signaling towards both kidney and liver aging.

overall_design: We did RNA-seq of podocytes from young (4-month-old) mice, old mice(21-month-old) treated with PD1 control antibody, and old mice treated with anti-PD1 antibody. All mice were male. We have 5 biological replicates per condition

first: Yuliang

last: Wang


title: Microglia-like cells derived from patients with panic disorder

status: Public on Sep 30 2022

city: Seongnam-si

first: Minsoo

last: Kwon

address: 335 Pangyo-ro

department: Pharmacology

country: South Korea

institute: CHA University

summary: We used a model to induce patient-derived microglia-like cells (iMGs) to clarify the molecular characteristics and function of Panic disorder patient-iMGs (PD-iMGs). We established iMGs from 14 PD patients and 10 healthy controls (non-psychiatric controls, HC). We analyzed the phenotype of the PD-iMGs by RNA sequencing. The PD-iMGs clustered together distinct from HC-iMGs. Gene set enrichment analysis revealed the involvement of cholesterol biosynthesis and steroid metabolism in PD-iMGs.

overall_design:
The human RNA sample which was collected from peripheral blood monocytes derived microglia-like cells of 10 Healthy control individuals and 14 Panic disorder patients were sequenced.

Please note that the previous processed data files (with incorrect gene symbols) have been replaced on Nov 15, 2022.

first: Min-Jung

last: You

first: Chan

last: Rim

first: Minji

last: Bang

first: Bohyun

last: Yang

first: Hui-Ju

last: Kim

first: Soyoung

last: Sung

first: Sang-Hyuk

last: Lee


title: Transcriptomic response of bioengineered human cartilage to parabolic flight microgravity is sex-dependent

city: Edmonton

first: Zhiyao

state: Alberta

country: Canada

institute: University of Alberta

summary: Spaceflight and simulated spaceflight microgravity induced osteoarthritic-like alterations at the transcriptomic and proteomic levels in the articular and meniscal cartilages of rodents. But little is known about the effect of spaceflight or simulated spaceflight microgravity on the transcriptome of tissue-engineered cartilage developed from human cells. In this study, we investigate the effect of simulated spaceflight microgravity facilitated by parabolic flights on tissue-engineered cartilage developed from chondrogenically differentiated human bone marrow mesenchymal stem cells obtained from age-matched female and male donors. Our bulk transcriptome data via RNA sequencing demonstrated that the engineered tissues responded to parabolic microgravity in a sex-dependent manner.

overall_design: Response of bioengineered human cartilage to parabolic flight microgravity

first: Aissiou

middle: K

last: Aissiou

first: Kirtan

last: Dhunnoo

first: Shankar

last: Jha

first: Rahul

last: Ravin

first: Melanie

last: Kunze

first: Hilda

middle: Z

first: David

middle: X

last: Li

first: Kinston

last: Wong

first: Adetola

middle: B

last: Adesida


title: ULK3 is a key determinant of the keratinocyte self-renewal and tumorigenesis

first: Sandro

last: Goruppi


title: Expression data from human endometrial stromal cells (HESCs) treated with PRP

status: Public on Sep 24 2022

city: Tokyo

first: Keiji

last: Kuroda

address: Nishi-shinjuku, 1-19-6, Shinjuku-ku

department: Center for Reproductive Medicine and Implantation Research

country: Japan

institute: Sugiyama Clinic Shinjuku

summary:
In IVF treatment, the effects of intrauterine platelet-rich plasma (PRP) infusion with increasing rate of successful pregnancy have been reported; however, the mechanisms that support embryo implantation remain unclear.
In the undifferentiated HESCs, PRP was found to strongly promote the gene expression associated with cell growth, tissue regeneration, proinflammatory response, and antibiotic effects. In decidualized HESCs, PRP was found to attenuate the gene expression involved in cell proliferation and inflammation by inhibiting the expression of PI3K signaling.

overall_design: HESCs were cultured and passaged equally into four cell culture dishes in each patient. Two were treated with PRP twice and the other two were treated with vehicle. Subsequently, two cultures with and without PRP were decidualized with cAMP and progesterone for 5 days. The gene expression in undifferentiated or decidualized HESCs with and without PRP was compared.


title: Expression profiling analysis reveals key microRNA–mRNA interactions in patients with transposition of the great arteries and systemic left and right ventricles [miRNA]

first: Masood

last: Abu-Halima

first: A

last: Meese

first: Hashim

last: Abdul-Khaliq


title: Identification and control for the effects of bioinformatic globin depletion on human RNA- seq differential expression analysis

status: Public on Oct 17 2022

city: Melbourne

first: Dylan

last: Sheerin

state: VIC

address: 1G Royal Parade

country: Australia

institute: WEHI

summary:
To compare the impact of haemoglobin depletion by hybridisation-based removal or bioinformatic removal of reads on the outcome of differential gene expression analysis.
This comparisons was performed using RNA-seq data from 58 human tuberculosis (TB) patient whole blood samples – 29 globin kit-depleted and 29 matched non-depleted – a subset of which were taken at TB diagnosis and at six months post-TB treatment from the same patient

overall_design: Comparative gene expression profiling analysis of whole blood RNA-seq data from TB patients before and after treatment and quantitative assessment of the effects of kit depletion or bioinformatic depletion on this outcome.


title: Canine head and neck cancer as a spontaneous, translational model for radio-immunology research

city: Fort Collins

first: Daniel

last: Regan

address: 1678 Campus Delivery

institute: Colorado State University

summary: The baseline immune landscape of spontaneous canine HNSCC tumors was asssessed using immunohistochemistry and nanostring gene expression profiling of 34 canine oral carcinoma tumors and two normal oral mucosal tissue samples.

overall_design: Formalin fixed paraffin embedded tissue samples from 33 dogs were analyzed, which included 34 tumor samples and 2 normal mucosal samples, with one dog providing both tumor and normal mucosal samples. Samples were anlayzed by immunohistochemistry for CD3, FoxP3, CD204, and CD79a. RNA was extracted for nanostring gene expression profiling using a custom designed panel of canine specific probes for 48 immune genes based on those published by Rooney et al. (2015).

first: Keara

last: Boss


title: KDM6B protects T-ALL cells from NOTCH1-induced oncogenic stress [Human RNAseq]

city: St Louis

first: Grant

middle: A

last: Challen

state: MO

address: 660 Euclid Avenue

department: Medicine

institute: Washington University School of Medicine

summary: Kdm6b mutant cells are at a survival disadvantage in NOTCH1- induced T-ALL

overall_design: Comparative gene expression profiling analysis of RNA-seq data for primary T-ALL patient samples that were targeted against AAVS1 or KDM6B using CRISPR/Cas9

first: Nancy

last: Issa

first: Aishwarya

last: Krishnan

first: Hassan

last: Bjeije

first: Hamza

last: Celik

first: Saranajith

last: Dunuwille

first: Won

last: Kyuh

first: Andrew

last: Young

first: Sammi

last: Burkart

first: Jason

last: Arand


title: Hepatic BCL6 and plasma triglycerides regulate sexual dimorphism in tissue tolerance [set 5]

first: Joni

last: Nikkanen

summary: Tissue tolerance is a sexually dimorphic trait. Here, we investigated the role of BCL6 in establishing hepatic chromatin landscape promoting sexually dimorphic tissue tolerance during E.Coli infection.

overall_design: Investigated the H3K27 acetylation in livers of Bcl6Flox/Flox and Bcl6Flox/Flox,Alb-Cre male and female mice infected with E.Coli and housed at +30ºC.

first: Yew

last: Leong

first: Ajay

last: Chawla


title: Hepatic BCL6 and plasma triglycerides regulate sexual dimorphism in tissue tolerance [set 4]

summary: Hepatic gene expression shows sexual dimorphism. Here, we investigated the role of BCL6 in establishing sexually dimorphic chromatin state and performed H3K27ac ChIP-seq from livers of female and male Ctrl and BCL6 liver knock-out mice.

overall_design: Investigated the H3K27 acetylation in livers of Bcl6Flox/Flox and Bcl6Flox/Flox,Alb-Cre male and female mice.


title: Disruption to the FOXO-PRDM1 axis resulting from deletions of chromosome 6 in acute lymphoblastic leukaemia

city: Newcastle Upon Tyne

first: Paul

last: Sinclair

state: Tyne and Wear

address: Level 6, Herschel Building, Newcstle university

department: Translational and Clinical Research Institute

country: United Kingdom

institute: Newcastle University

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

overall_design: Refer to individual Series


title: T cells specific for alpha-myosin drive immunotherapy related myocarditis

status: Public on Sep 22 2022

city: Nashville

first: Margaret

middle: L

last: Axelrod

state: TN

address: 2200 Pierce Ave, 777 PRB

institute: Vanderbilt University

summary: Single cell RNA and TCR sequencing of murine hearts and human alpha-myosin expanded blood

sample_organism:
Homo sapiens
Mus musculus

platform_organism:
Homo sapiens
Mus musculus

overall_design: Single cell RNA and TCR sequencing


title: Fetal genetic findings for fetal growth restriction without structural malformations at a territory referral center: 10-year experience

status: Public on Sep 20 2022

city: Fuzhou

first: Xiaoqing

last: Wu

address: 18 daoshan road, Gulou district

institute: Fujian Maternity and Child Health Hospital, Affiliated Hospital of Fujian Medical University

type:
Genome variation profiling by SNP array
SNP genotyping by SNP array

summary: We retrospectively reviewed 488 fetuses who diagnosed with FGR and without structural malformation during a 10-year period. A total of 19 (3.9%) cases of chromosomal anomalies were detected, including 11 cases of numerical abnormalities, 5 of structural abnormalities, and 3 of mosaicism. We classified the cohort into cases diagnosed at ≤24, 25-28, 29-32, and > 32 weeks of gestation according to the onset gestations; isolated FGR, FGR with soft markers, and FGR with nonstructural anomalies according to different ultrasound findings; high and low-risk maternal serum screening (MSS) groups based on the MSS results. The results suggested that abnormal karyotypes were more frequently detected in cases diagnosed at ≤24 weeks (7.2%), cases with soft markers (5.2%), and cases with high-risk MSS (7.5%) than in other groups within each classification. Among cases with normal karyotype, additional 4.2% of clinically relevant aberrations were detected by SNP array. The incremental yields in cases diagnosed at ≤24 weeks (6.5%), cases with soft markers (9.5%), and cases with high-risk MSS (12.0%) were higher than those in other groups within each classification. We concluded that fetal chromosomal aberration is an important etiology for FGR without structural malformation, and plays an important role in pregnancies decision-making. SNP array improves the detection of genetic anomalies especially in fetuses diagnosed at ≤24 weeks, fetuses with soft makers, and fetuses with high risk of MSS.

overall_design:
We retrospectively reviewed 488 fetuses who diagnosed with FGR and without structural malformation. Conventional karyotyping was performed on all subjects, and SNP array was performed on 272 of them. The cohort was classified into groups diagnosed at ≤24, 25-28, 29-32, and > 32 weeks of gestation. According to the ultrasonography, they were grouped into isolated FGR, FGR with soft markers, and FGR with nonstructural anomalies. Based on the maternal serum screening (MSS), they were categorized into high-risk and low-risk MSS groups. The rates of abnormal karyotypes and incremental yield of clinically significant aberrations detected by SNP array were compared among groups in different classifications.
-----------------------------------------------
Submitter states: "Some CEL files were lost because of the damage of hard disc."
This submission includes 10 CEL files only

first: Liangpu

last: Xu


title: Analysis of genes bound by ULK3 and of H3K27 histone modification plus/minus ULK3 silencing in SCC13 cells

first: Sandro

last: Goruppi

summary: We report high-throughput profiling of genes bound by ULK3 and of H3K27 histone modification plus/minus ULK3 silencing in squamous cell carcinoma SCC13 cells .

overall_design: Identification of ULK3-bound genes and examination of active chromatin mark ± ULK3 silencing in SCC13 cells

first: Andrea

last: Clocchiati

first: Giulia

last: Bottoni

first: Min

last: Ma

first: Gian

middle: P

last: Dotto


title: mRNA profiles of CD43++c-kit+, CD43+c-kit- and CD43-c-Kit- AML1-ETO9a murine leukemic bone marrow cells

status: Public on Oct 03 2022

city: Shanghai

first: Mengxi

last: Wang

address: 197# Rui Jin Road II, Shanghai 200025 CHINA.

institute: Shanghai Institute of Hematology

summary: We discovered a spontaneous differentiation path characterized by CD43 and c-Kit in the AE9a murine model, where the leukemia-initiating potential is lost while leukemic cells display features of erythroid maturation. Therefore, we sorted out CD43++c-Kit+, CD43+c-Kit- and CD43-c-Kit- AE9a leukemic cells for RNA-sequencing analyses to determine the underlying transcriptome.

overall_design: CD43++c-Kit+, CD43+c-Kit- and CD43-c-Kit- AML1-ETO9a murine leukemic bone marrow cells were sorted out. mRNA profiles were generated by deep sequencing, in triplicate, using  Illumina HiSeq 4000. The sequence reads that passed quality filters were analyzed at the transcript isoform level with two methods: Burrows–Wheeler Aligner (BWA) followed by ANOVA (ANOVA) and TopHat followed by Cufflinks. qRT–PCR validation was performed using  SYBR Green assays.

first: Meng-xi

first: Li

last: Yan

first: Jiang

last: Zhu


title: The Injections of Mitochondrial Fusion Promoter M1 during Proestrus Disrupt the Progesterone Secretion and the Estrous Cycle in the Mouse.

status: Public on Sep 16 2022

city: Taipei City

first: Yi-Fan

last: Jiang

address: No.1, Sec. 4, Roosevelt Road

country: Taiwan

institute: National Taiwan University

summary: Mitochondrial fusion promotor, M1, was used to study the impact of mitochondria dynamics in the female reproductive system. The M1 treatment in mice can lead to acute and reversible disruption of estrous cycles in vagina smears. The ovarian samples were collected after the control and M1 injections on the evening of proestrus. The comparative gene expression profiling analysis of RNA-seq data was performed.

overall_design: Comparative gene expression profiling analysis of RNA-seq data for mouse ovaries after the treatments of M1 or control on the day of proestrus.


title: Cell polarity opposes Jak-STAT mediated Escargot activation that drives intratumor heterogeneity in a Drosophila tumor model

status: Public on Sep 19 2022

city: New Orleans

first: Wu-Min

last: Deng

state: LA

address: 1700 Tulane Avenue

department: School of Medicine, Department of Biochemistry

institute: Tulane University

summary: In proliferating neoplasms, microenvironment-derived selective pressures promote tumor heterogeneity by imparting diverse capacities for growth, differentiation and invasion. However, what makes a tumor cell respond to signaling cues differently from a normal cell is not well understood. In the Drosophila ovarian follicle cells, apicobasal-polarity loss induces heterogenous epithelial multilayering. When exacerbated by oncogenic-Notch expression, this multilayer displays an increased consistency in the occurrence of morphologically distinguishable cells adjacent to the polar follicle cells. Polar cells release the Jak-STAT ligand Unpaired (Upd), in response to which, neighboring polarity-deficient cells exhibit a precursor-like transcriptomic state. These cells activate the Snail-family transcription factor Escargot (Esg), among several regulons that we identify using single-cell transcriptomics. We also ascertain a similar relationship between Upd and Esg in normally-developing ovaries, where establishment of polarity determines early follicular differentiation. Overall, our results indicate that epithelial-cell polarity acts as a gatekeeper against microenvironmental selective pressures that drive heterogeneity.

overall_design: Whole-tissue RNA-Seq (2 replicates per genotype; 2 time-points - 24h and 96h) of tjTS>GFP (Control) and tjTS>lglRNAi, tjTS>NICD, tjTS>Upd, tjTS>Upd+lglRNAi and tjTS>NICD+lglRNAi (Samples) and single-cell RNA-Seq (1 replicate; 1 time-point - 72h) of w1118 cells (Control) of the Drosophila ovary and tjTS>lglRNAi, tjTS>Upd+lglRNAi and tjTS>NICD+lglRNAi cells (Samples) of the Drosophila ovary. Single-cell RNA-Seq: 10x Genomics CHROMIUM Single Cell 3’ Solution V2 Chemistry and Sequencing platform: Illumina NovaSeq 6000.

first: Deeptiman

last: Chatterjee


title: The novel long noncoding RNA Lnc19959.2 modulating triglyceride metabolism associated genes through interaction with Purb and hnRNPA2B1 (RNA-seq data set)

status: Public on Sep 11 2022

first: dongsheng

last: xiao

address: No.151 Libing Road, Zhangjiang Hi-Tech Park Pudong, Shanghai 201203, P.R. China

institute: Shanghai Biotechnology Corporation

summary: High triglycerides can lead to atherosclerotic cardiovascular disease. Long noncoding RNAs (lncRNAs) are currently consider to have vital and wide range of biological functions, but the molecular mechanism underlying TG metabolism remains poorly understood. To identify novel lncRNAs differentially expressed in rat liver with hypertriglyceridemia using transcriptome sequencing and elucidated the function role in TG metabolism. In our study, we identified a novel lncRNA, Lnc19959.2, which was highly expression in rat liver with hypertriglyceridemia. Knockdown of lnc19959.2 has profound TG lowering effects in vitro and vivo. Subsequently genome-wide analysis identified that knockdown of Lnc19959.2 caused deregulation of many genes during TG homeostasis. Further mechanism studies reveal that Lnc19959.2 specifically bound to Purb to up-regulate expression of Apoa4, while bound to hnRNPA2B1 to down-regulate the expression of Cpt1a, Tm7sf2 and Gpam, respectively. In the upstream pathway, palmitate acid up-regulated CCAAT/Enhancer-Binding Protein Beta (Cebpb) facilitates its binding to promoter region of Lnc19959.2, which resulted in significant promotion of lnc19959.2 transcriptional activity. Our findings provide novel insights into transcriptional regulation of TG homeostasis by a novel lncRNA. This newly identified lncRNA could be exploited as novel therapeutic targets for hypertriglyceridemia.

first: Jing

first: Dao

last: Xiang

first: Shuai

last: Mei

first: Yuanchao

last: Jing

first: Dating

last: Sun

first: Chen

last: Chen

first: Dong

last: Hu

first: Shiyang

last: Li

first: Huihui

first: Yan

first: Hu

last: Ding

middle: W


title: Expression data of A549 Fra-2 overexpressing cells

status: Public on Sep 23 2022

city: Columbus

first: Carlo

middle: M.

last: Croce

state: Ohio

address: 460 West 12th Avenue

department: Department of Cancer Biology and Genetics

institute: The Ohio State University

summary:
Fra-2 belongs to the activated protein-1 (AP-1) family and is involved in the mechanisms of resistance to platinum in ovarian cancer and to anti-EGFR therapy in NSCLC.
We used microarrays to identify genes potentially regulated by Fra-2 transciptional activity.

overall_design: A549 cell lines were transfected with pCMV6-Entry-Fra2 (Myc-DDK-tagged) and pCMV6-Entry as control (ORIGENE, Rockville, MD) and, after 48 hours, RNA was collected and isolated.

first: Francesca

last: Lovat

first: Gian

last: Rampioni Vinciguerra


title: Cortical bulk RNA sequencing of Trem2 H157Y knock-in mouse models

status: Public on Sep 08 2022

city: Jacksonville

first: Tadafumi

middle: Clark

last: Ikezu

address: 4500 San Pablo Rd

institute: Mayo Clinic

summary: We performed cortical bulk RNA-seq aiming to study how Trem2 H157Y mutation affect the overall transcriptomic profiles in the absence or presence of amyloid pathology. We identified differentially expressed genes and significant modules in the comparison of Hom and WT mice in the non-amyloid and amyloid cohorts, separately. In general, while there were only three DEGs in the non-amyloid cohort, 183 DEGs emerged responding to amyloid pathology, including 177 downregulated genes and 6 upregulated genes. These DEGs were found to related to neuroinflammatory pathway. Although no significant module related to genotype was identified in the non-amyloid cohort through weighted gene co-expression network analysis, we discovered an immune process related module in the amyloid cohort network and this module was downregulated in Hom mice and correlated with the amyloid pathological readout.

overall_design: A total of 40 samples were run in both lanes of the flow cell. These samples were separated into non-amyloid (20) and amyloid (20) cohort. Each cohort includes five mice per sex for each of the two genotypes, wild type (WT) and homozygous (Hom) mice.

first: Wenhui

last: Qiao

last: Clark Ikezu


title: Regulatory mechanisms and metabolic changes of miRNA during leaf color change in the bud mutation branches of Acer pictum subsp. mono.

status: Public on Sep 06 2022

city: Beijing

first: Baoli

last: Lin

address: No.7 Beinong Road, Shigezhuang Street

institute: College of Landscape Architecture, Beijing Agricultural College

summary: To reveal the molecular mechanism of leaf color changes in Acer pictum subsp. mono, this study was conducted on bud-transformed branches, analyzing the transcriptome and small RNAs of Acer pictum subsp. mono leaves and performing miRNA-mRNA association analysis on differentially expressed mRNAs and miRNAs.

overall_design:
We then performed gene expression profiling using data obtained by RNA-seq of six groups of material from both AG and AR periods.
Comparative gene expression profiling of RNA-seq data from leaves of wild branches and leaves of mutant branches of Acer pictum subsp. mono.(AG,AR)

first: Baolil

first: Jinteng

last: Cui


title: The use of tissue microRNAs to distinguish indolent and aggressive forms of prostate cancer

status: Public on Sep 01 2022

city: Brno

first: Jaroslav

last: Juracek

address: Kamenice 5

country: Czech Republic

institute: CEITEC MU

summary: The low sensitivity or specificity of current parameters for prostate cancer detection leads to overdiagnosis and overtreatment of the disease. MicroRNAs are small non-coding RNAs whose level can reflect clinical and biological characteristics of the tumor. In the study, our objective was to identify miRNAs associated with disease aggressiveness, which can supplement risk stratification systems.

overall_design: A global miRNA profiling was performed on FFPE samples from indolent and aggressive prostate cancer. Within two-level validation, the prognostic potential of miRNAs associated with disease aggressiveness was evaluated.

first: Ondrej

last: Slaby


title: Transcriptome from mouse Ts65Dn adult hippocampi and entorhinal cortices

city: ILLKIRCH

first: Yann

last: HERAULT

address: 1 rue Laurent Fries

country: France

institute: IGBMC/PHENOMIN-ICS

summary: We have created the Ts66Yah a new model for Down syndrome or T21, derived from the Ts65Dn. Ts66Yah does not contain a set of  genes present in 3 copies that are not linked to T21. On this model (Ts66), we performed an RNA seq analysis on 2 structures (hippocampus and entorhinal cortex, ref: S18276) and we have done the same experiment on the Ts65Dn line to compare the 2 models. For this we sampled the hippocampus (hippo) and the entorhinal cortex (EntCortex) from 6 wild-type control male littermate animals and 6 males trisomic individual (Ts66 or Ts65).

overall_design: 12 individuals, 6 control and 6 Ts, 2 brain regions Hippocampus and Entorhinal cortex

last: Herault

first: Arnaud

last: Duchon


title: Transcriptome from mouse Ts66Yah adult hippocampi and entorhinal cortices

overall_design: 11 individuals, 5 control and 6 Ts, 2 brain regions Hippocampus and Entorhinal cortex


title: Expression data from U251 RSK1 Knockout and RSK2 Knockout cell lines

city: Honolulu

first: Won Seok

last: Yang

state: HI

address: University of Hawaii Cancer Center, 701 Ilalo st, Lab 454

institute: University of Hawaii Cancer Center

summary:
The 90 kDa ribosomal S6 kinases (RSKs) are serine threonine kinases comprising four isoforms. The isoforms can have overlapping functions in regulation of migration, invasion, proliferation, survival, and transcription in various cancer types.
We delineate RSK isoform-specific transcriptional gene regulation by comparing transcription programs in RSK1 and RSK2 knockout cells using microarray analysis.

overall_design: To determine if RSK1 and RSK2 have specific roles in gene expression, NT, RSK1 knockout and RSK2 knockout U251 cells were for RNA extraction and hybridization on Affymetrix microarrays. Cells were serum starved (0.1% FBS) overnight to minimize RSK activity, then stimulated with epidermal growth factor (EGF) (100 ng/ml) for 5 hours generating 6 samples for analysis: NT-DMSO, NT-EGF, RSK1 Knockout-DMSO, RSK1 Knockout-EGF, RSK2 Knockout-DMSO and RSK2 knockout-EGF.

first: Won

middle: S

first: Maisel

middle: J

last: Caliva

first: Vedbar

last: Khadka

first: Maarit

last: Tiirikainen

first: Michelle

last: Matter

first: Youping

last: Deng

first: Joe

last: Ramos


title: Single-cell transcriptome profiling of the stepwise progression of head and neck cancer

status: Public on Aug 31 2022

city: Suwon

first: Hyun Goo

last: Woo

address: 164 Worldcup-ro Yeongtong-gu

institute: Ajou University School of Medicine

summary: Head and neck squamous cell carcinoma (HNSCC) undergoes stepwise progression from normal tissue to metastasized tumors. To comprehensively delineate the heterogeneity of tumor cells and their interactions during the progression of HNSCC, we employed single-cell RNA-seq (scRNA-seq) profiling for the tissues of normal, leukoplakia, HNSCC, and metastasized HNSCC. We identified novel clones of malignant cells expressing LGALS7B and fibroblasts expressing CXCL8, and the abundance of these cells in the tumor tissue was associated with poorer prognostic outcomes. In addition, we demonstrated that fibroblasts in leukoplakia and tumor tissue express COL1A1, which interacts with CD44+ malignant cells, facilitating HNSCC progression. CD4+FOXP3+ regulatory T cells expand in leukoplakia and express LAIR2 with collagen stimulation, which may provide a favorable microenvironment for tumor progression. In conclusion, stromal and immune cell interactions play critical roles in the stepwise progression of HNSCC, and we have identified steps during HNSCC progression for possible therapeutic interventions

overall_design: Single-cell transcriptome profiling from 37 tissue specimens of non-tumoral surrounding normal tissue (NL, n = 9), leukoplakia (LP, n = 4), primary cancer (CA, n = 20), and metastatic tumors in lymph nodes (LN, n = 4)

first: H

middle: G


title: Bovine intramuscular adipocytes RNA-seq

city: Xianyang

first: Xinhao

last: Ma

state: Shaanxi

address: No. 3, Taicheng Road

institute: Northwest A&F University

type: Non-coding RNA profiling by high throughput sequencing

summary: RNA sequencing was performed to  obtain a landscape of mRNA, circRNA, lncRNA, and miRNA of bovine intramuscular adipocytes in 4 differentiation periods.

overall_design: Intramuscular adipocytes mRNA, circRNA, lncRNA, and miRNA profiles of adipogenic differentiation at 0d, 3d, 6d and 9d (n=3).

first: Xinran

first: Linsen

last: Zan


title: Tissue-specific modifier alleles determine Mertk loss-of-function traits

status: Public on Aug 26 2022

city: New Haven

first: Yemsratch

middle: Tadesse

last: Akalu

state: CT

address: 300 Cedar Street

department: Immunobiology

institute: Yale University

summary: Knockout (KO) mouse models play critical roles in elucidating biological processes behind disease-associated or disease-resistant traits. As a consequence of gene KO, mice display certain phenotypes. Based on insight into the molecular role of said gene in a biological process, it is inferred that the particular biological process causally underlies the trait. This approach has been crucial towards understanding the basis of pathological and/or advantageous traits associated with Mertk KO. MERTK is a receptor tyrosine kinase with a critical role in phagocytosis of apoptotic cells or cellular debris. Therefore, early-onset, severe retinal degeneration was described to be a direct consequence of failed phagocytosis of photoreceptor outer segments by retinal pigment epithelia. Similarly, enhanced anti-tumor immunity was inferred to result from the failure of macrophages to dispose cancer cell corpses, resulting in a pro-inflammatory tumor microenvironment. Here we report that the loss of Mertk alone is not sufficient for retinal degeneration. This trait only manifests when the function of the paralog Tyro3 is concomitantly lost. Additionally, the dramatic resistance against two syngeneic mouse tumor models observed in Mertk KO cannot, at least entirely, be ascribed to the loss of Mertk. The widely used Mertk KO carries multiple coincidental changes in its genome that affect the expression of a number of genes, including Tyro3. Nonetheless, neither Tyro3, nor macrophage phagocytosis by alternate genetic redundancy, accounts for the absence of anti-tumor immunity in two independent Mertk KOs. Collectively, our results indicate that context-dependent epistasis of independent modifier alleles determine Mertk KO traits.

overall_design: We performed gene expression profiling analysis using data obtained from RNA-sequencing of bone-marrow-derived macrophages (BMDMs) and retinal pigment epithelial (RPE) cells from C57BL/6, Mertk-/-V1, Mertk-/-V2 and Mertk-/-V3 mice.

middle: T

first: Maria

middle: E

last: Mercau

first: Marleen

last: Ansems

first: Sagie

last: Wagage

first: Lindsey

middle: D

last: Hughes

first: James

last: Nevin

first: Emily

last: Alberto

last: Liu

first: Li-Zhen

last: He

first: Diego

last: Alvarado

first: Tibor

last: Keler

first: Yong

last: Kong

first: William

middle: M

last: Philbrick

first: Silvia

middle: C

last: Finnemann

first: Antonio

last: Iavarone

first: Anna

last: Lasorella

first: Carla

middle: V

last: Rothlin

first: Sourav

last: Ghosh


city: Abu Dhabi

first: Piergiorgio

last: Percipalle

state: Abu Dhabi

address: Saadiyat Campus, Abu Dhabi

department: Biology Department, Science Division

country: United Arab Emirates

institute: New York University Abu Dhabi

summary: ATAC-Seq analysis of beta actin knockout mouse embryonic fibroblasts expressing NLS-tagged beta-actin to study impact of actin levels on chromatin accessibility

overall_design: ATAC sequencing was performed on 2 replicates

first: Syed

last: Raza Mahmood


title: Transcriptome analysis of developing seeds from Mtabi4 Tnt1 insertion mutants

status: Public on Sep 13 2022

city: Beaucouze

first: Julia

last: Buitink

address: 42 rue Georges Morel

department: BAP

institute: INRAE

summary: ABI4 (MtrunA17_Chr5g0437371) is an AP2 transcription factor that is upregulated during seed maturation. To identify genes that are regulated by this transcription factor in the model legume Medicago truncatula, Tnt1 insertion mutants were identified and RNA sequencing was performed on two abi4 mutants and the wild type seeds at 13 DAP, 24 DAP and mature seeds.

overall_design: Three replicates of 50 seeds harvested from different plants were sequenced for two Tnt1 insertion mutants, NF10440 (hsfa9-1) and NF13157 (Mthsfa9-2) in the R108 background and the wildtype R108.

last: Zinsmeister

first: David

last: Lalanne

first: Olivier

last: Leprince


title: Small molecule screen reveals pathways that regulate C4 secretion in stem-cell derived astrocytes.

status: Public on Sep 17 2022

city: Cambridge

first: Matthew

middle: Thomas

last: Tegtmeyer

state: MA

address: 75 Ames St

department: Stanley Center

institute: Broad Institute

summary: In the brain, the complement system plays a crucial role in the immune response and in synaptic elimination during normal development and disease. Here, we sought to identify pathways that modulate the production of complement component 4 (C4), recently associated with an increased risk of schizophrenia. To design a disease-relevant assay, we first developed a rapid and robust 3D protocol capable of producing large numbers of astrocytes from pluripotent cells. Transcriptional profiling of these astrocytes confirmed the homogeneity of this population of dorsal fetal-like astrocytes. Using a novel ELISA-based small molecule screen, we identified epigenetic regulators, as well as inhibitors of intracellular signaling pathways, able to modulate C4 secretion from astrocytes. We then built a Connectivity Map to predict and validate additional key regulatory pathways, including one involving c-Jun-kinase (JNK). This work provides a foundation for developing therapies for CNS diseases involving the complement cascade.

overall_design: Biological replicates of astrocytes differentited from human stem-cells (IPSCs, 1016A, n=3 ,ESCs, Hues8 n=3 and H1 n=2) were analyzed using scRNAseq

first: Francesca

last: Rapino

first: Ted

last: Natoli

first: Francesco

last: Limone

first: Erin

last: O'Connor

first: Jack

last: Black

last: Tegtmeye

last: Chen

first: Erika

last: Norabuena

first: Juhin

last: Narula

first: Dane

last: Hazelbaker

first: Lindy

last: Barrett

first: Alison

last: O’Neil

first: Ursula

middle: K

last: Beattie

first: Jessica

last: Thanos

first: Heather

last: de Rivera

first: Roy

middle: H

last: Perlis

first: Steven

last: McCarroll

first: Beth

last: Stevens

first: Aravind

last: Subramanian

first: Ralda

last: Nehme

first: Lee

last: Rubin


status: Public on Sep 09 2022

first: baoli

last: lin

address: No.7 Beinong Road

institute: Beijing Agricultural College

overall_design:
We then performed gene expression profiling using data obtained by miRNA-seq of six groups of material from both AG and AR periods.
Comparative gene expression profiling of miRNA-seq data from leaves of wild branches and leaves of mutant branches of Acer pictum subsp. mono.(AG,AR)

first: Baolil

last: Lin

first: Jinteng

last: Cui


title: Sequencing analysis of beta-actin KO MEFs expressing NLS-beta-actin

first: Piergiorgio

last: Percipalle

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

overall_design: Refer to individual Series


title: Macrophages trigger injury-induced hepatocyte reprogramming via IL-6/gp130/STAT3 axis

status: Public on Aug 24 2022

first: Lijian

last: Hui

address: yueyang road 320

department: SIBCB

institute: CEMCS, CAS


title: Chromosome 9p21.3 Coordinates Cell Intrinsic and Extrinsic Tumor Suppression [scRNA-seq]

city: New York

first: Yu-Jui

last: Ho

state: New York

address: 417 E 68th St

department: Cancer Biology & Genetics Program

institute: Memorial Sloan Kettering Cancer Center

summary: Somatic chromosomal deletions are prevalent in cancer, yet their effects are poorly understood. The most prominent homozygous deletions affect chromosome 9p21.3 and eliminate the CDKN2A/B tumor suppressor genes, thus disabling a cell intrinsic barrier to tumorigenesis. However, half of 9p21.3 deletions encompass a cluster of 16 type I interferons (IFNs) whose co-deletion remains unexplored. To functionally dissect 9p21.3 and other genomic deletions, we developed MACHETE (Molecular Alteration of Chromosomes with Engineered Tandem Elements), a genome engineering strategy that enables flexible modeling of megabase-sized deletions. Applying MACHETE to a syngeneic mouse model of pancreatic cancer, we show that concomitant loss of the IFN cluster with Cdkn2a/b enhanced immune evasion, metastasis, and immunotherapy resistance compared to Cdkn2a/b deletions alone. Mechanistically, IFN co-deletion disrupted type I IFN signaling in the tumor microenvironment, leading to marked changes in infiltrating immune cells and escape from CD8+ T cell surveillance, effects largely driven by the poorly understood interferon epsilon (Ifne). These results reveal how IFN-encompassing 9p21.3 deletions disable cell intrinsic and extrinsic tumor suppression, thereby providing a pervasive route for immune evasion, metastasis, and immunotherapy resistance. Our study provides a framework for interrogating large deletion events in cancer and beyond.

overall_design: sc RNA-seq analysis was performed on CD45+ cells sorted from from KrasG12D; sgP53; dS or KrasG12D; sgP53; dL tumors, which were harvested from immune-competent mice treated with control IgG or anti-IFNAR1 blocking antibody.

first: Francisco

last: Barriga

first: Kaloyan

last: Tsanov

first: Yu

last: Jo

first: Noor

last: Sohail

first: Amy

last: Zhang

first: Timour

last: Baslan

first: Alexandra

last: Wuest

first: Isabella

last: Del Priore

first: Brigita

last: Meskauskaite

first: Geulah

last: Livshits

first: Direna

last: Alonso-Curbelo

first: Janelle

last: Simon

first: Almudena

last: Chaves-Perez

first: Dafna

last: Bar-Sagi

first: Christine

middle: A

last: Iacobuzio-Donahue

first: Faiyaz

last: Notta

first: Ronan

last: Chaligne

first: Roshan

last: Sharma

first: Dana

last: Pe'er

first: Scott

last: Lowe


title: Endothelial Extracellular Vesicles Contribute to the Malignant Plasticity of Prostate Cancer cells in Concert with Endogenous Twist1

status: Public on Aug 22 2022

city: Norfolk

first: Allison

middle: Heath

last: Mathiesen

state: VA

address: 700 W Olney Rd, Department of Physiology

institute: Eastern Virginia Medical School


title: Overexpression of ZmSUS1 gene alters the content and composition of endosperm starch in maize (Zea mays L.)

status: Public on Sep 07 2022

city: Jinan

first: Panpan

last: Li

address: Daxue Road 3501

institute: Qilu University of Technology

summary: Cereal crops accumulate starch in seeds as an energy reserve. Sucrose synthase (SuSy) plays an important role in grain starch synthesis. In this study, ZmSUS1 was transformed into maize inbred line KN5585, and transgenic plants were obtained. Compared with the control, the content and activity of SuSy were significantly increased, the amylose content in mature seeds of transgenic maize increased by 41.1-69.2%, the total starch content increased by 5.0-13.5%, The 100-grain weight increased by 19.0-26.2% and the average diameter of starch granules increased by 10.8-17.2%. These results indicated that overexpression of ZmSUS1 can significantly improve the traits of maize kernels and obtain new lines with high amylose content. It was also found that ZmSUS1 may increase the amylose content by regulating the expression of Shrunken2 (Sh2) and Brittle2 (Bt2) which encodes endosperm ADP-glucose pyrophosphorylase (AGPase) size subunits, and the expression of Granule bound starchsynthase1 (GBSS1) and Starch synthase1 (SS1) which encodes starch synthase. This study proved the important role of ZmSUS1 in maize starch synthesis, and provided a new technology strategy for improving corn starch content and yield.

overall_design:
In this study, ZmSUS1 (Zm00001d047253) was transformed into a maize inbred line to study the effect of its overexpression on the structure and content of maize starch and the expression of genes related to starch synthesis.
A transgenic strain (T) was selected with its non-transgenic negative control (CK) for RNA-seq analysis, with three biological replicates selected each. RNA is extracted from corn kernels after 10 days of pollination.

first: Haizhen

last: Ma

first: Ning

last: Xiao

first: Yuqing

last: Zhang

first: Tianyu

last: Xu

first: Tao

last: Xia


title: Gene expression of PC3ML, metastatic prostate cancer cells, with or without HAMVEC EV C, HAMVEC EV PIC, or ATEV treatment and/or expressing varying levels of endogenous TWIST1

summary: The aim of this study was to explore the potential link between inflammation-induced endothelial dysfunction and prostate cancer phenotypic plasticity in vitro, and to explore the role of endogenous Twist1

overall_design: In this study PC3ML expressing either wild type, deficient or surplus levels of Twist1 were either untreated or treated with extracellular vesicles (EV)derived from control or proinflammatory-cytikine treated human adipose microvascular endothelial cells or from EV collected from adipose tissue of subjects undergoing bariatric surgery. RNA was then isolated from the cells and gene expression assessed using the NanoString Pan Cancer Progression panel.

first: Anca

last: Dobrian

first: Ryan

last: Huyck


title: Effect of Exogenous Retinoic Acid on human iPSCs derived intestinal organoids

status: Public on Sep 02 2022

city: Charleston

first: Jorge

last: Munera

state: SC

address: 173 Ashley Avenue

institute: Medical University of South Carolina

summary: Retinoic acid promotes the in vitro growth, patterning and improves the cellular composition of human pluripotent stem-cell-derived intestinal organoids

overall_design: 35-day old human intestinal organoids (HIO) generated from clump were collected for RNA-Seq. analysis. One group of HIO were cultured in basic gut medium with EGF (HIO control)  and the other group of HIO were treated with EGF plus retinoic acid (HIO + RA).

last: Qu

first: Braxton

last: Jeffcoat


title: mRNA transcriptome analyses of the functions of DDX6-mediated pathways during EpiLC induction

city: Mishima

first: Yumiko

last: Saga

state: Shizuoka

address: 1111 Yata

department: Department of Gene Function and Phenomics

institute: National Institute of Genetics

summary: DDX6 is an RNA helicase and involved in various post-transcriptional regulatory processes. Although DDX6 is an evolutionarily well conserved central player in post-transcriptional gene regulation, its function in embryonic development remains obscure. In this study, we have identified the crucial functions of DDX6 during early mouse embryogenesis. However, due to its wide range of involvement, the more detailed dissection of DDX6-mediated functions was required to pinpoint which specific DDX6 function is important. For this purpose, we selected a key gene of each well-known DDX6 pathway, generated KO ES line, then made cDNA libraries of ESC and EpiLC Day2 samples to investigate transcriptomic differences during the very early differentiation processes of embryonic pluripotent cells.

overall_design: There are total 5 genotype groups: WT, Ddx6 KO, Eif4enif1 KO, Dcp2 KO, Dgcr8 KO.  For each genotype, mRNA profiles of two ESC libraries (Three Dgcr8 KO ESC libraries), three EpiLC Day2 libraries.

first: Jessica

last: Kim

first: Masafumi

last: Muraoka

first: Hiroshi

last: Mori

first: Atsushi

last: Toyoda


title: MTFR2 shapes a barrier of immune microenvironment in hepatocellular carcinoma

city: Changsha

first: Hong

last: Shen

state: Hunan

address: Xiangya Road

department: Department of Oncology

institute: Xiangya Hospital

summary: Hepatocellular carcinoma (HCC) is a leading cause of cancer-related death in the world. Mitochondrial fission regulator 2 (MTFR2) is involved in the development of various cancers. However, the roles of MTFR2 in HCC remain unknown. In this study, we conducted a comprehensive analysis of MTFR2 in HCC, which was generated from integrative MTFR2 analyses of eight HCC cell lines, and three datasets (public dataset, real-world dataset, immunotherapy dataset) derived from bulk HCC tissues, survival and immunotherapy data. We demonstrated that the expression level of MTFR2 is up-regulated in HCC, leading to poor prognosis. MTFR2 is positively correlated with the level of immune cell infiltration, multiple immune checkpoints and immunotherapy response prediction pathways, and act important role in cancer-immunity cycle. In conclusion, our work indicates that MTFR2 can shape a barrier of immune microenvironment and result in poor prognosis in hepatocellular carcinoma, but the immune barrier may be broken by immunotherapy.

overall_design:
Comparative gene expression profiling analysis of RNA-SEq data for anti-PD-1 immunotherapy in patients with hepatocellular carcinoma.

*** Submitter declares that raw data are not available due to patient privacy concerns. ***


title: Spatial transcriptomics of in vivo invasive trancheobronchitis biopsies obtained from patients with influenza-associated pulmonary aspergillosis or COVID-19-associated pulmonary aspergillosis

city: Seattle

first: Wei

last: Yang

state: WA

address: 530 Fairview Ave N

institute: Nanostring

summary: To assess whether transcriptional differences exist in the epithelial tissue and the inflammatory infiltrate of invasive Aspergillus tracheobronchitis in patients with severe influenza or severe COVID-19, we performed GeoMx spatial transcriptomics on four biopsy samples in total: two of patients with influenza-associated pulmonary aspergillosis (IAPA) and two of patients with COVID-19-associated pulmonary aspergillosis (CAPA). Several regions of interest (ROIs) were delineated in each biopsy sample, and transcriptomic data was derived of each of these ROIs using GeoMx with a whole transcriptome atlas with SARS-CoV-2 spike-in.

sample_organism: Severe acute respiratory syndrome coronavirus 2

overall_design: Four in vivo tracheobronchial biopsies of invasive Aspergillus tracheobronchitis were obtained from patients with IAPA (n=2) and CAPA (n=2). ROIs were selected in epithelial tissue and in the (subepithelial) inflammatory infiltrate.

first: Simon

last: Feys

first: Agostinho

last: Carvalho

first: Johan

last: van Weyenbergh

first: Joost

last: Wauters


title: mRNA transcriptome analysis of Ddx6 knockout embryos

summary: DDX6 is an RNA helicase and involved in various post-transcriptional regulatory processes. Although DDX6 is an evolutionarily well conserved central player in post-transcriptional gene regulation, its function in embryonic development remains obscure. To study this, we examined Ddx6 knockout mouse embryos and pluripotent cell lines. E8.5 Ddx6 mutants exhibited gastrulation defects. To transcriptomically identify the existing cell population in E8.5 mutant embryos and further find the possible causes of this defect, we performed RNA-seq analysis with E8.5 embryo cDNA libraries.

overall_design: mRNA profiles of one E7.5 wild-type embryo library, one E8.5 wild-type embryo library, and two E8.5 Ddx6 KO embryo libraries


title: CD70 as an actionable immunotherapeutic target in recurrent glioblastoma and its microenvironment

city: Hamilton

first: Sheila

last: Singh

state: ON

address: 1280 Main Street West

department: Biochemistry and Biomedical Sciences

institute: McMaster University

summary: We have used our established Glioblastoma cell models and gene expression analyses to characterize gene wild-type and CD70 knockdown GBM cell lines

overall_design: We utilized early passage Glioblastoma cell lines derived from primary patient samples of Glioblastoma in our work, as these samples are enriched for Brain Tumor Initiating Cells (BTICs) that are believed to initiate tumor formation. Briefly, we transduced each cell line with either shGFP or shCD70-knockdown lentiviral vectors, and confirmed knockdown of CD70 by flow cytometry. These lines were minimally cultured, collected, and sent for RNA sequencing analysis.

first: Mathieu

middle: P

last: Seyfrid

first: William

last: Maich

first: Vaseem

last: Shaikh

first: Chitra

last: Venugopal

first: Minomi

last: Subapanditha

first: Kevin

middle: R

last: Brown

first: Jason

last: Moffat


title: Hdac1 and Hdac2 ChIP-Seq of isolated E16.5 nephron progenitor cells [ChIP-seq]

city: New Orleans

first: Hongbing

last: Liu

address: 1430 Tulane Ave

institute: Tulane University

summary: ChIP-Seq was employed to study the important roles of Hdac1 and Hdac2 in the regulation of gene expression during nephrogenesis

overall_design: The nephron progenitor cells were isolated from E16.5 kidneys of wild type mice and cultures for two massages. After crosslinking with formaldehyde, the samples were shipped to Diagendo for ChIP-Seq service


title: Expression data from unstimulated vs. anti-CD40 stimulated cDC1 from WT mouse skin draining lymph node

city: Saint Louis

first: Kenneth

last: Murphy

state: MO

address: Clinical Science Research Building, 7th Floor, Room 7701A, Campus Box 8118

department: Pathology & Immunology

institute: Washington University School of Medicine

summary: We used microarrays to identify gene targets of CD40 signaling in mouse cDC1.

overall_design: cDC1s from skin draining lymph nodes of WT mice were sort-purified for RNA extraction and hybridization on Affymetrix microarrays. We sought to obtain and compare gene expression signatures for cDC1 populations in the presence or absence of CD40 stimulation.

first: Renee

last: Wu


title: Lack of GPR180 ameliorates hepatic lipid depot via downregulation of mTORC1 signaling

status: Public on Aug 25 2022

city: Shimotsuke

first: Sadahiko

last: Iwamoto

state: Tochigi

address: Yakushiji 3311-1

department: Center for Molecular Medicine

institute: Jichi Medical University

summary: Our previous genome-wide association study to explore genetic loci associated with lean nonalcoholic fatty liver disease (NAFLD) in Japan suggested four candidate loci, which were mapped to chr6, chr7, chr12 and chr13. The present study aimed to identify the locus involved functionally in NAFLD around the association signal observed in chr13.

overall_design: Chromosome conformation capture assay and a database survey suggested the intermolecular interaction among DNA fragments in association signals with the adjacent four coding gene promoters. The four genes were further screened by knockdown (KD) in mice using shRNA delivered by an adeno-associated virus vector (AAV8), and KD of G protein-coupled receptor 180 (Gpr180) showed amelioration of hepatic lipid storage. Gpr180 knockout (KO) mice also showed ameliorated hepatic and plasma lipid levels without influencing glucose metabolism after high-fat diet intake. Comparative gene expression profiling analysis of RNA-seq data for C57BL6 wild type mice and knockout mice fed with high fat diet.

first: Ken

last: Yoshida

first: Kazuha

last: Yokota


title: Mitochondrial PARP1 Regulates NAD+-dependent Poly ADP-ribosylation on Mitochondrial Nucleoids

status: Public on Aug 20 2022

city: Baltimore

first: Jong-Hyuk

last: Lee

state: Maryland

address: 251 Bayview BLVD

institute: National Institute of Health

summary: Poly ADP-ribose (PAR) polymerases (PARPs) play fundamental roles in multiple DNA damage recognition and repair pathways. Persistent nuclear PARP activation causes cellular NAD+ depletion and exacerbates cellular aging. However, very little is known about mitochondrial PARP (mtPARP) and PARylation. The existence of mtPARP is controversial, and the biological roles for mtPARP induced mitochondrial PARylation are unclear. Here, we demonstrate the presence of PARP1 and PARylation in purified mitochondria. The addition of the PARP1 substrate NAD+ to isolated mitochondria induces PARylation which is suppressed by PARP inhibitor olaparib treatment. Mitochondrial PARylation was also evaluated by enzymatic labeling of terminal ADP-ribose (ELTA) labeling. To further confirm the presence of mtPARP1, we evaluated mitochondrial nucleoid PARylation by ADP ribose-chromatin affinity purification (ADPr-ChAP) . We observed that NAD+ stimulated PARylation and TFAM occupancy on the mtDNA regulatory region D-loop, inducing mtDNA transcription. These findings suggest that PARP1 is integrally involved in mitochondrial PARylation and NAD+ dependent mtPARP1 activity contributes to mtDNA transcription regulation.

overall_design: TFAM ChIP or ADPr-ChAP were performed with isolated mitochondria from HeLa cells that are treated with DMSO (control), NAD+, NAD+ with olaparib.

first: Vilhelm

last: Bohr


title: A cis-regulatory lexicon of DNA motif combinations mediating cell type-specific gene regulation [MPRA]

status: Public on Aug 17 2022

city: Stanford

first: Margaret

last: Guo

state: CA

address: 269 Campus Dr. CCSR Room 2150

institute: Stanford University

summary:
Abstract: Gene expression is controlled by transcription factors (TFs) that bind cognate DNA motifs in cis-regulatory elements (CREs), however, the combinations of motifs that mediate cell type-specific gene regulation are undefined. Chromatin accessibility, TF footprinting, and H3K27ac-dependent DNA looping data were generated to identify 7,531 cell type-specific CREs across 15 normal human cell types. A co-enrichment framework nominated 838 cell type-specific, recurrent heterotypic DNA motif combinations (DMCs), which were functionally validated using massively parallel reporter assays. Compared to their normal counterparts, cancer cells induced DMCs linked to neoplasia-enabling processes that operate in normal cells while also engaging entirely new DMCs. These data identify a cis-regulatory combinatorial DNA motif lexicon for cell type-specific gene regulation in diverse normal and diseased human cells.
Purpose: To identify a cis-regulatory combinatorial DNA motif lexicon mediating cell type-specific gene regulation in diverse normal and diseased human cells, matched RNA-seq, chromatin accessibility profiling via ATAC-seq, and enhancer-promoter looping via H3K27ac HiChIP was performed in 15 primary human cell types and 6 human cancer cell lines. Processed and raw data for all cell types can be found in this repository. Squamous cell carcinoma cell line raw and processed data can be found at Jung, et al. "XXX". All biological replicates (n=2) are merged.

sample_organism:
Homo sapiens
synthetic construct

platform_organism:
Homo sapiens
synthetic construct

overall_design:
4 primary human cell type and 2 human cancer cell line MPRA mRNA profiles with 3 biological replicates in vitro
NOTE FROMS SUBMITTER: For the melanocytes and keratinocytes raw data, these are primary human samples so we can’t release the raw data files but we can release all processed files.

first: Laura

last: Donohue


title: A cis-regulatory lexicon of DNA motif combinations mediating cell type-specific gene regulation [HiChIP-Seq]

overall_design:
15 primary human cell type and 2 malignant melanoma H3K27ac HiChIP profiles with 2 or 3 biological replicates in vitro
NOTE FROMS SUBMITTER: For the melanocytes and keratinocytes raw data, these are primary human samples so we can’t release the raw data files but we can release all processed files.


title: A cis-regulatory lexicon of DNA motif combinations mediating cell type-specific gene regulation [ATAC-Seq]

overall_design:
15 primary human cell type and 3 malignant melanoma cell line open chromatin (ATAC-seq) profiles with 2 biological replicates in vitro
NOTE FROMS SUBMITTER: For the melanocytes and keratinocytes raw data, these are primary human samples so we can’t release the raw data files but we can release all processed files.


title: A cis-regulatory lexicon of DNA motif combinations mediating cell type-specific gene regulation [RNA-Seq]

overall_design:
15 primary human cell type and 3 human malignant melanoma cell line mRNA profiles with 2 biological replicates in vitro
NOTE FROMS SUBMITTER: For the melanocytes and keratinocytes raw data, these are primary human samples so we can’t release the raw data files but we can release all processed files.


title: A cis-regulatory lexicon of DNA motif combinations mediating cell type-specific gene regulation

overall_design: Refer to individual Series


title: ZFP90 drives initiation of colitis-associated colorectal cancer using a microbiota-dependent strategy

status: Public on Aug 14 2022

city: Shanghai

first: Ji-Xuan

last: Han

address: 145 Middle Shandong Road

institute: Renji Hospital, Shanghai Jiao-Tong University School of Medicine

summary:
Chronic inflammation and gut microbiota dysbiosis are risk factors for colorectal cancer. In clinical practice, inflammatory bowel disease (IBD) patients have a greatly increased risk of developing colitis associated colorectal cancer (CAC). However, the basis underlying the initiation of CAC remains to be explored. Systematic filtration through existing genome-wide association study (GWAS) and conditional deletion of Zfp90 in CAC mice model indicated that Zfp90 was a putative oncogene in CAC development.
Strikingly, depletion of gut microbiota eliminated the tumorigenic effect of Zfp90 in CAC mice model. Moreover, fecal microbiota transplantation demonstrated Zfp90 promoted CAC depending on gut microbiota. Combining 16s rDNA sequencing in feces specimens from CAC mice model, we speculated that Prevotella copri-defined microbiota might mediate the oncogenic role of Zfp90 in the development of CAC. Mechanistic studies revealed Zfp90 accelerated CAC development through Tlr4-Pi3k-Akt-Nf-κb pathway. Our findings elucidated the crucial role of Zfp90-microbiota-Nf-κb axis in creating a tumor-promoting environment and suggested therapeutic targets for CAC prevention and treatment.

overall_design: Examination of colon epithelium gene expression from two groups: (1) Zfp90fl/f with AOM-DSS treatment; (2) Zfp90△IEC with AOM-DSS treatment.

first: Zhi-Hang

last: Tao

first: Chen-Yang

last: Yu

first: Jing-Yuan

last: Fang


title: miRNA cargo of extracellular vesicles in the proinflammatory obese adipose environment

first: Allison

last: Mathiesen

summary: miRNA detected in Extracellular Vesicles obtained from adipose tissue of patients undergoing bariatric surgery or from human adipose microvascular endothelial cells  (HAMVEC) either untreated or treated with proinflammatory cytokines (PIC)

overall_design: In this study we sought to characterize the miRNA cargo of obese adipose tissue extracellular vesicles and that of human adipose microvascular endothelial cells in the presence or absence of proinflammatory cytokines.

first: Anca

last: Dobrian

last: Mathisen

first: Ryan

last: Huyck


title: Development and transdifferentiation into inner hair cells require Tbx2

status: Public on Aug 09 2022

city: Beijing

first: Zhiyong

last: Liu

address: 7 Science Park Road ZGC Life Science Park

institute: National Institute of Biological Sciences, Beijing

summary: Atoh1 is essential for the development of both outer hair cells (OHCs) and inner hair cells (IHCs) in the mammalian cochlea. Whereas Ikzf2 is necessary for OHC development, the key gene required for IHC development remains unknown. We found that deletion of Tbx2 in neonatal IHCs led to their transdifferentiation into OHCs by repressing 26.7% of IHC genes and inducing 56.3% of OHC genes, including Ikzf2. More importantly, persistent expression of Tbx2 coupled with transient Atoh1 expression effectively reprogramed non-sensory supporting cells into new IHCs expressing the functional IHC marker vGlut3. The differentiation status of these new IHCs was considerably more advanced than that previously reported. Thus, Tbx2 is essential for IHC development, and co-upregulation of Tbx2 with Atoh1 in supporting cells represents a new approach for treating deafness related to IHC degeneration.

overall_design: Adult cochlear inner hair cells (IHCs) at P30 (P30_WT IHCs)  were manually picked  and subjected to smart-seq HT library construction. The transcriptomic comparision between P30_WT IHCs and P30_WT OHCs (from our previous report) identified that Tbx2 is a transcriptional factor that highly expressed in P30_WT IHCs, but not in  P30_WT OHCs. We further confirmed that Tbx2 is persistently expressed in IHC lineage from emrbyonic to adult ages. To determine the roles of Tbx2 in IHCs, we constructed the conditional Tbx2 cko model where Tbx2 was specifically deleted in neonatal IHCs. Our phenotypic analysis demonstrates that IHCs tend to become OHCs when Tbx2 is deleted. Thus, the Tbx2 -/- IHCs were defined as induced OHCs (iOHCs). Next, by the same smart-seq HT method,  we compared the gene profiles between wild type IHCs at P14 (P14_WT IHCs) and those iOHCs at P14 (P14_iOHCs). The overal cell cluster  and trajectorary analysis support that the iOHCs globally behave adult OHCs.

first: Zhenghong

last: Bi

first: Xiang

last: Li

first: Minhui

last: Ren

first: Yunpeng

last: Gu

first: Tong

last: Zhu

first: Shuting

first: Guangqin

last: Wang

first: Suhong

last: Sun

first: Yuwei


title: HAND1 knockdown disrupts trophoblast global gene expression

status: Public on Aug 03 2022

city: Gainesville

first: Helen

middle: N

last: Jones

state: Florida

address: 1345 Center Dr

department: Physiology and FUnctional Genomics

institute: University of Florida

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


title: HAND1 knockdown disrupts trophoblast gene expression in vitro in Bewo cells

status: Public on Aug 02 2022

summary: Congenital heart disease (CHD) affects nearly 1% of births annually, and neonatal and perinatal outcomes in cases of CHD are strongly impacted by pregnancy outcomes. CHD pregnancies carry increased risk of developing pathologies of abnormal placentation including fetal growth restriction, preeclampsia, preterm birth, and stillbirth. HAND1 is a gene associated with CHD.  In this study, we aimed characterize the mechanistic impacts of disrupting HAND1 on human placenta trophoblast cell lines.

overall_design: To silence HAND1 gene expression, BeWo cells, a choriocarcinoma model of human cytotrophoblasts, were treated for 96 h with HAND1/2 siRNA. Cells were harvested and mRNA isolated. RNA sequencing was performed using the Illumina NextSeq 550 platform (single end reads 85-101bp, read depth 25M). The Galaxy Bioinformatic Platform was used for quality control, alignment and generation of read counts. Normalization and differential gene expression analyses were conducted using general linear modeling in edgeR packages. Statistical significance was determined using a log2 fold change cut off >1.0 or <-1.0 and unadjusted ≤0.05. Overrepresentation analysis was performed using Panther DB for Reactome pathways and GO Biological Processes, and String DB for protein association network analysis.


title: Antibody from Single Human VH-rearranging Mouse Potently Neutralizes All SARS-CoV-2 Variants Through BA.5 by Inhibiting Membrane Fusion

status: Public on Jul 28 2022

city: Boston

first: Frederick

middle: W

last: Alt

address: 1 Blackfan Circle

department: Program in Cellular and Molecular Medicine

institute: Boston Children's Hospital

summary: Here, we describe a mouse model in which the primary B cell receptor (BCR) repertoire is generated solely through V(D)J recombination of a human VH1-2 heavy chain (HC) and, substantially, a human Vk1-33 light chain (LC).  Thus, primary humanized BCR repertoire diversity in these mice derives from immensely diverse HC and LC antigen-contact complementarity-region-3 (CDR3) sequences generated de novo by non-templated junctional modifications during V(D)J recombination. We assayed the V usage and CDR3 diversity in this mouse model by HTGTS-repertoire sequencing.  Immunizing this human VH1-2/Vk1-33-rearranging model with prototype SARS-CoV-2 spike protein immunogens elicited several VH1-2/Vk1-33-based nAbs.  Of these, SP1-77 potently and broadly neutralized all SARS-CoV-2 variants through BA.5.  Cryo-EM studies revealed that SP1-77 binds RBD away from the ACE2 receptor-binding-motif via a striking CDR3-dominated mode of recognition.  Lattice-light-sheet-microscopy-based studies confirmed that SP1-77 did not block ACE2-mediated viral attachment or subsequent endocytosis, but rather blocked membrane fusion.  The SP1-77 binding epitope and neutralization mechanism may offer additional strategies for designing vaccines that robustly neutralize emerging SARS-CoV-2 variants.

overall_design: High-thoughput sequencing of splenic B cell receptor repertoire

first: Sai

last: Luo

first: Jun

last: Zhang

first: Alex

last: Kreutzberger

first: Amanda

last: Eaton

first: Robert

middle: J

last: Edwards

first: Changbin

last: Jing

first: Hai-Qiang

last: Dai

first: Gregory

last: Sempowski

first: Kenneth

last: Cronin

first: Robort

last: Parks

first: Adam

middle: Y

last: Ye

first: Karayoun

last: Mansouri

first: Maggie

last: Barr

first: Novalia

last: Pishesha

first: Aimee

last: Williams

first: Lucas

last: Francisco

first: Anand

last: Saminathan

first: Hanqin

last: Peng

first: Himanshu

last: Batra

first: Lorenza

last: Bellusci

first: Surender

last: Khurana

first: S

last: Alam

first: David

last: Montefiori

first: Kevin

middle: O

last: Saunders

first: Ming

last: Tian

first: Hidde

last: Ploegh

first: Thomas

last: Kirchhausen

first: Bing

last: Chen

first: Barton

middle: F

last: Haynes


title: GPX8 regulates clear cell renal cell carcinoma tumorigenesis through promoting lipogenesis by NNMT

status: Public on Aug 01 2022

city: Seoul

first: Sunghyouk

last: Park

state: Not US or Canada

address: Bldg 143, Room 302 College of Pharmacy Seoul National University, Gwanak 1

department: Natural Products

institute: Seoul National University

summary: By analyzing RNAseq data from TCGA in ccRCC and metabolomics data from CCLE, we identified the strong correlation of GPX8 with the lipid and glycogen metabolism, which are highly upregulated in ccRCC. We validated this observation by knocking out GPX8 in Caki1 (ccRCC cell line). Using transcript profiling, we confirmed the association of GPX8 with de novo lipogenesis and suppressed fatty acid oxidation. Mechanically, from RNA-seq data we also found the decrease of NNMT upon GPX8 KO, which functions as the downstream of GPX8 and regulates the lipid phenotype in ccRCC.

overall_design: GPX8 was permanently knocked out using CRISPR-Cas9 in Caki1 cell line. RNA samples from two groups (GPX8-KO Caki1 and WT-Caki1) were extracted for RNA sequencing.

first: Tin Tin

last: Nguyen


title: Nonconverters exhibit differential transcriptional signatures compared to converters.

status: Public on Aug 21 2022

city: Tyler

first: Tanmoy

last: Mukherjee

state: TX

department: Pulmonary Immunology

institute: University of Texas Health Science Center at Tyler

summary: Here, we determined the transcriptional signature of the above groups of donor PBMCs after Mtb antigen ESAT-6 and CFP-10 stimulation.

overall_design: We obtained freshly isolated PBMCs from converters (n = 3) and nonconverters (n = 3) at baseline and during follow-up and cultured them in the presence and absence of ESAT-6 and CFP-10 for 48 h and the global gene expression pattern was determined using whole transcriptome sequencing.

first: Deepak

last: Tripathi

first: Vijaya

middle: L

last: Valluri


title: Accurate simultaneous sequencing of genetic and epigenetic bases in DNA

status: Public on Jul 24 2022

city: Cambridge

first: Páidí

last: Creed

address: B400, The Trinity Building Chesterford Business Park, Saffron Walden

institute: biomodal limited

summary: We present a single-base-resolution sequencing methodology that will simultaneously sequence complete genetics and complete epigenetics in a single workflow. The approach is non-destructive to DNA and provides a digital readout of bases, which we exemplify by simultaneous sequencing of G, C, T, A, and 5mC/5hmC (5-letter sequencing) or 5mC and 5hmC (6-Letter sequencing). We demonstrate sequencing of human genomic DNA and also cell-free DNA taken from a blood sample of a cancer patient. The approach is accurate, requires low DNA input and has a simple workflow and analysis pipeline. We envisage it will be versatile across many applications in life sciences.

overall_design: 5-letter and 6-letter sequencing technologies unambiguously resolve the 4 genetic bases with the 5-th letter being 5mC or 5hmC (also referred to as modC) or the 5-th and 6-th letter being 5mC and 5hmC, respectively. This experiment evaluates the performance of these technologies and compares 5-letter sequencing with Whole-genome Bisulfite Sequencing and Enzymatic Methyl Sequencing.

first: Casper

last: Lumby

middle: M

last: Morley

first: Joanna

middle: D

last: Holbrook


title: Divergent clonal differentiation trajectories of T cell exhaustion

status: Public on Jul 25 2022

first: Ansuman

middle: T

last: Satpathy

address: 300 Pasteur Drive

department: Pathology