title: Dual targeting of TGF-β and PD-L1 with bifunctional anti-PD-L1 /TGF-β RII agents in recurrent cervical cancer

status: Public on Oct 01 2022

city: Jinan

first: Wenxiong

last: Sun

address: No.107 West Wenhua Road, Jinan, 250001, China

institute: Qilu Hospital, Cheeloo College of Medicine, Shandong University

summary:
Purpose: To find out the patients who are most sensitive and effective to the anti-PD-L1 and TGF-β bifunctional fusion protein in the treatment of recurrent cervical cancer.
Patients and methods: We report two cases of recurrent cervical cancer treated with the anti-PD-L1 and TGF-β bifunctional fusion protein. We described the clinical course, clinical characteristics, and genetic characteristics of the two patients, and analyzed the changes of gene expression in the two patients after treatment.
Results: Although PD-L1 expression and HPV status were same in the two patients, the treatment effect of two patients with recurrent cervical cancer was different, according to the evaluation of enhanced computed tomography (CT), one was partial response (PR) and the other was progressive disease (PD), which may indicate that PD-L1 expression and HPV status of patients is not enough to predict the effectiveness of the anti-PD-L1 and TGF-β bifunctional fusion protein treatments. Then, we demonstrated that the changes of peripheral blood lymphocytes of two patients during the treatment had different trends. Moreover, number of alterable genes in PR patient is much greater than that in PD patient, indicating PR patient may be more sensible to the anti-PD-L1 and TGF-β bifunctional fusion protein treatments. Total 4844 genes changing-fate gene set selected which is believed conducting anti-cancer function during the anti-PD-L1 and TGF-β bifunctional fusion protein treatments. Furthermore, we identified that changing-fate genes were correlated with female reproductive organ cancer, infectious disease, inflammatory disease, immune system, indicating these genes may conducting anti-cancer, anti-inflammation and immune function.
Conclusion: Anti-PD-L1 and TGF-β bifunctional fusion protein is feasible for the treatment of recurrent cervical cancer. Multi-center, large-sample prospective clinical studies are still needed to further explore the efficacy of anti-PD-L1 and TGF-β bifunctional fusion protein in recurrent cervical cancer and screen appropriate patients, so as to achieve the maximum survival benefit of patients.

overall_design: Examination the changes of gene expression in the two patients after anti-PD-L1 and TGF-β bifunctional fusion protein treatment.

first: Jin

last: Peng


title: APOE4 drives transcriptional heterogeneity and maladaptive immunometabolic responses of astrocytes (bulk RNA-Seq)

status: Public on Oct 20 2022

city: Lexington

first: Joshua

middle: M

last: Morganti

state: KY

address: 789 S. Limestone St

department: Sanders-Brown Center on Aging

country: USA

institute: University of Kentucky

type: Expression profiling by high throughput sequencing

summary: Apolipoprotein 4 (APOE4), is the strongest genetic risk allele associated with the development of late onset Alzheimer’s disease (AD). Across the CNS, astrocytes are the predominant expressor of Apoe while also being critical mediators of neuroinflammation and cerebral metabolism. APOE4 has been consistently linked with dysfunctional neuro-immunometabolism, however insights into the molecular constituents driving these responses remain unclear. Utilizing complimentary approaches across humanized ApoE expressing mice and isogenic IPS astrocytes, we demonstrate that harboring ApoE4 alters astrocyte immunometabolic response to pro-inflammatory stimuli. Our findings demonstrate that ApoE4-expressing astrocytes acquire distinct transcriptional repertoires at the single-cell and spatially-resolved domains, which driven, in-part, by preferential utilization of the cRel transcription factor. Further, inhibiting cRel translocation abrogated inflammatory-induced glycolytic shift and ultimately resulted in significantly dampened glycolysis-associated metabolites in tandem with mitigating production of multiple pro-inflammatory cytokines. Altogether, our findings elucidate novel cellular underpinnings by which ApoE4 drives maladaptive immunometabolic responses of astrocytes.

overall_design: Isogenic APOE33 and APOE44 astrocytes (see 10.1016/j.cell.2022.05.017) were seeded in 24 well plate at a density of ~109k cells/well. Cells were treated with vehicle or 3ng/mL IL-1a, 30ng/mL TNF, and 400ng/mL C1q for 4 hours. Following treatment, media was apirated, cells washed with sterile DPBS. Following wash, cells were lysed with RLTplus buffer and RNA harvested per manufacturer's suggested protocol (Qiagen # 74034).


title: Distalised kidney organoids

status: Public on Sep 23 2022

city: Parkville

first: Sean

last: Wilson

state: Victoria

address: 50 Flemington Road

country: Australia

institute: MCRI

summary: Distalised organoid samples at Day 14 and Day 21 of culture. Day 21 cultures have RSPO1 addition either at Day 7 or Day 14 of culture.

overall_design: Single cell RNA-seq generated on a 10x Chromium genomics platform from iPSC-derived human kidney organoids. Each sample represents 6 pooled organoids derived from a single well of a transwell plate, generated from individual iPSC-derived reporter lines and harvested at either Day 14 (D14) or Day 21 (D21) of the differentiation protocol.

first: Pamela

last: Kairath

first: Melissa

last: Little


title: The prostate stromal transcriptome and aggressive and lethal prostate cancer

status: Public on Oct 11 2022

city: Boston

first: Yinglu

last: Zhou

state: MA

address: 450 Brookline Ave

institute: Dana-Farber Cancer Institute

summary: RNA sequencing (Illumina TruSeq Exome Capture) of 272 tumor-adjacent and 120 benign-adjacent macrodissected prostate stromal samples from 293 men from the Health Professionals Follow-up Study and Physicians’ Health Study.

overall_design: 272 tumor-adjacent and 120 benign-adjacent macrodissected prostate stromal samples from 293 male patient, with other pathological information collected, such as Gleason scores, lethal level and cribriform

first: Svitlana

last: Tyekucheva

first: Kathryn

middle: L

last: Penney


title: MBD5 and MBD6 stabilize the BAP1 complex and promote BAP1-dependent cancer

status: Public on Sep 15 2022

city: Chicago

first: Lu

last: Wang

state: Illinois

address: 303 E. Superior Street Simpson Querrey 7-414

department: Biochemistry and Molecular Genetics

institute: Northwestern University

type: Genome binding/occupancy profiling by high throughput sequencing

summary: The BRCA1-associated protein 1 (BAP1) is a ubiquitin carboxy-terminal hydrolase (UCH), which forms a multi-protein complex with different epigenetic factors such as ASXL1-3, and FOXK1/2. At chromatin, BAP1 catalyzes the removal of mono-ubiquitination on histone H2AK119 in collaboration with other subunits within the complex, and therefore functions as a transcriptional activator. However, the crosstalk between different subunits and how these subunits impact BAP1 function remains unclear. Here, we report the identification of the methyl-CpG-binding domain proteins 5 and 6 (MBD5 and MBD6) that bind to the C-terminal PHD fingers of the large scaffold subunits ASXL1-3 and stabilize the BAP1 complex at chromatin. We further identified a previously uncharacterized Drosophila protein, the six-banded (SBA), as the ortholog of human MBD5/6. We demonstrated the core module of the BAP1 complex is structurally and functionally conserved during the evolution from Drosophila (Calypso/ASX/SBA) to human cells (BAP1/ASXL/MBD). Dysfunction of the BAP1 complex induced by the misregulation/mutations in each subunit is frequent in human cancer. In BAP1-dependent human cancers, MBD6 tends to be a dominant form. Depletion of MBD6 leads to a global loss of BAP1 occupancy at chromatin, resulting in a reduction of BAP1-dependent gene expression and tumor growth in vitro and in vivo. In summary, our study has uncovered MBD5/6 as important regulators of the BAP1 complex and transcription, and sheds light on the therapeutic potential of targeting MBD5/6 in human cancer.

overall_design: This study aims to provide mechanistic insight into the function of MBD5/6 in BAP1 complex .

first: Zibo

last: Zhao


title: Influence of vaccination and time on gene expression of healthy backgrounded beef cattle

status: Public on Aug 29 2022

city: Canyon

first: Matthew

last: Scott

state: TX

address: 3201 Russell Long Blvd

institute: Texas A&M University

summary: Twelve clinically healthy backgrounded cattle (n=6 vaccinated, n=6 non-vaccinated), over four time points (median age in days: 107, 114, 183, 230) were selected for whole blood (Tempus Blood RNA Tubes) mRNA sequencing via NovaSeq 6000 S4 workflow. Sequenced raw reads (~35M/sample) were analyzed for the influence of time (immunological development) and vaccination with a commercial modified live viral multivalent vaccine on host gene expression.

overall_design:
Comparative time-course RNA-Seq analysis on lysed whole blood samples across four time points. Cattle (n=12) were evenly distributed based on vaccine administration at median day 107 and boostering at median day 183, or no vaccination.

Grant:
#2019-67015-29845
Title: "Impact of management decisions during the cow-calf, backgrounding, and feedlot phases of beef production on BRD morbidity and mortality risks"
Funding source: USDA National Institute of Food and Agriculture (NIFA) Agriculture and Food Research Initiative (AFRI).

middle: A


title: H3K4me3 CUT&Tag - Jmjd3-scKO, Utx-scKO, Tdt-Ctrl, IgG-His

status: Public on Aug 04 2022

city: Madison

first: Jeffrey

last: Dilworth

email: jdilworth@ohri.ca, fdilworth@wisc.edu

state: WI

address: 1111 Highland Ave - WIMR II 4518

department: Cell and Regenerative Biology

institute: University of Wisconsin - Madison

summary: Stem cells reside in specialized niches that play a critical role in modulating their fate. Supporting cells in the niche instruct fate changes to the stem cells through epigenetic enzymes that transduce cell signaling to modify gene expression. Recent studies showed that the innate immune response to muscle injury alters the muscle stem cell (MuSC) niche, it remains unknown how MuSC adapt to the modified milieu to mediate muscle repair. Here we show that the epigenetic enzyme JMJD3 coordinates MuSC adaptation to the regenerative niche in a non-cell autonomous manner where it modifies their extracellular matrix to integrate signaling that stimulates exit of quiescence. Genomics and transcriptomics approaches identified the hyaluronic acid (HA) synthesis enzyme Has2 as a key JMJD3 target gene that allows MuSCs to integrate signals from the regenerative niche. Overall, we identified a specific role for JMJD3 in regulating the expression of genes that allow MuSCs to adapt to the modified niche of regenerating muscle. We aim to determine the differential occupancy of histone H3 lysine 4 trimethyl mark muscle satellite stem cells isolated from JMJD3scKO, UTXscKO and Wild-type mice.

overall_design: CUT&Tag was performed on muscle satellite cells isolated from hindlimb muscles at 30 hrs post cardiotoxin injury.

first: Kiran

last: Nakka

first: F

middle: J


title: Maternal transcription factor TCF12 mediates fertilization and zygotic genome activation during early embryonic development

status: Public on Aug 17 2022

city: Hangzhou

first: Lan-Rui

last: Cao

state: Zhejiang

address: 866 Yu Hang Tang Rd

department: Life Sciences Institute

country: China

institute: Zhejiang University

summary: To investigate the physiological function of TCF12 in oocyte maturation and preimplantational development, we crossed Tcf12fl/fl mice with Gdf9-Cre mice to specifically delete Tcf12 from the primordial follicle stage. We then performed gene expression profiling analysis using data obtained from RNA-seq on Tcf12fl/fl and Tcf12fl/fl;Gdf9-Cre growing GV oocytes (gGO), fully grown GV oocytes (fGO), embryos at 2-cell and 4-cell stage.

overall_design: Comparative gene expression profiling analysis of RNA-seq data for Tcf12fl/fl and Tcf12fl/fl;Gdf9-Cre samples.

first: Chi

last: Zhang

first: Zuo-Qi

last: Deng

first: Zhi-Yan

last: Jiang

first: Yun-Wen

last: Wu

first: Jing

last: Li

first: Heng-Yu

last: Fan


title: Next Generation Sequencing Facilitates Quantitative Analysis of NP1 and NP1/CRTCHA Gut Transcriptomes

status: Public on Aug 10 2022

first: HANSONG

last: DENG

address: RM 5O1, BLDG 1, # 817 ZHENGLI RD, YANGPU DISTRICT

institute: Tongji University

summary: Differential expression analysis used the DESeq2 Bioconductor package, a model based on the negative binomial distribution. the estimates of dispersion and logarithmic fold changes incorporate data-driven prior distributions, Padj of genes were setted <0.05 to detect differential expressed ones.Our study represents the detailed analysis of of NP1 and NP1/CRTCHA drosophila gut transcriptomes, with biologic replicates, generated by RNA-seq technology.Transcriptome analysis indicated that the genes involved in proteasome assembly, ROS scavengers, and protein folding were highly enriched among those differentially expressed genes (DEGs) in CRTC overexpressing (CRTCOE) intestines.

overall_design: Gut mRNA profiles of 3-5-day old NP1/+ and NP1/+;UASCRTCHA/+ drosophila

first: Hansong

first: Youjie

last: Yin


title: Jmjd3-Lab UTX-Lab CUT&Tag


title: H3K27me3 CUT&Tag - Jmjd3-scKO, Utx-scKO, Tdt-Ctrl, IgG-His


title: WGBS of primary and recurrent ovarian cancer tumors with and without BRCA1/2 mutations

status: Public on Jul 31 2022

city: Los Angeles

first: Michelle

last: Jones

state: CA

address: 8700 Beverly Blvd

institute: Cedars Sinai Medical Center

type: Methylation profiling by high throughput sequencing

summary: WGBS was generated for a cohort of ovarian cancer patients to identify DNA methylation changes between primary and recurrent ovarian cancer tumors from patients with and without BRCA1/2 mutations

overall_design: We performed whole genome bisulfite sequencing in 62 primary and  recurrent  tumors  from  28  patients  with  stage  III/IV  high  grade  serous  ovarian  cancer (HGSOC), of which 11 patients carried germline, pathogenic BRCA1and/or BRCA2mutations

first: Nicole

last: Gull

middle: R

first: Simon

last: Gayther


title: Jak2V617F Reversible Activation Shows an Essential Requirement for Jak2V617F in Myeloproliferative Neoplasms

status: Public on May 25 2022

city: Philadelphia

first: Robert

last: Bowman

state: PA

address: 421 Curie Blvd

department: Cancer Biology

institute: University of Pennsylvania School of Medicine

summary: Janus kinases (JAKs) mediate cytokine signaling, cell growth and hematopoietic differentiation. Gain-of-function mutations activating JAK2 signaling are seen in the majority of  myeloproliferative neoplasm (MPN) patients, most commonly due to the JAK2V617F driver allele. While clinically-approved JAK inhibitors improve symptoms and outcomes in MPNs, remissions are rare, and mutant allele burden does not substantively change with chronic JAK inhibitor therapy in most patients. This has been postulated to be due to incomplete dependence on constitutive JAK/STAT signaling, alternative signaling pathways, and/or the presence of cooperating disease alleles; however we hypothesize this is due to the inability of current JAK inhibitors to potently and specifically abrogate mutant JAK2 signaling. We therefore developed a conditionally inducible mouse model allowing for sequential activation, and then inactivation, of Jak2V617F from its endogenous locus using a Dre-rox/Cre-lox dual orthogonal recombinase system. Deletion of oncogenic Jak2V617F abrogates the MPN disease phenotype, induces mutant-specific cell loss including in hematopoietic stem/progenitor cells, and extends overall survival to an extent not observed with pharmacologic JAK inhibition. Furthermore, reversal of Jak2V617F in MPN cells with antecedent loss of Tet2 abrogates the MPN phenotype and inhibits mutant stem cell persistence suggesting cooperating epigenetic-modifying alleles do not alter dependence on mutant JAK/STAT signaling. Our results suggest that mutant-specific inhibition of JAK2V617F represents the best therapeutic approach for JAK2V617F-mutant MPN and demonstrate the therapeutic relevance of a dual-recombinase system to assess mutant-specific oncogenic dependencies in vivo.

overall_design: Gene expression profiling was performed on sorted lineage negative, Sca1+, Kit+ (LSK) and megakaryocyte-erythroid progenitor cells (MEPs). These were cells were sorted from JAK2 V617F mice where tamoxifen (TAM)-mediated Cre activation results in loss of the JAK2 V617F allele. LSKs and MEPs were sorted from either vehicle treated mice, after 3 days of TAM, after 7 days of TAM, or after 7 days of JAK2 inhibition with Ruxolitinib.

first: Andrew

last: Dunbar

first: Ross

last: Levine


title: Platinum chemotherapy induces diverse evolutionary trajectories in high grade serous ovarian cancer

status: Public on Aug 01 2022

city: London

first: Eleni

last: Maniati

address: John Vane Science Centre, Charterhouse Square

department: Barts Cancer Institute

country: United Kingdom

institute: Queen Mary University of London

summary: Cisplatin- and carboplatin-resistant high-grade serous ovarian cancer (HGSC) cells were generated and new lines were created from single cell clones. All cells were derived from a common ancestral line, Ovcar4. RNA sequencing was performed to examine transcriptional changes related to acquisition of platinum resistance.

overall_design: RNA sequencing on HGSC cell lines OVCAR4, Ov4Cis and Ov4Carbo  as well as two cell lines derived from single cell Ov4Carbo clones (Ov4Carbo4 and Ov4Carbo7). The cells were cultured in vitro and three biological replicates were performed per cell line.

first: Joseph

last: Hoare

first: Helen

last: Hockings

first: Ashley

last: Browne

first: Jayeta

last: Saxena

first: Francesco

last: Nicolini

last: Lockley


title: RNA-Seq and CUT&Tag of satellite stem cells

first: Jeffrey

last: Dilworth

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

overall_design: Refer to individual Series


title: Single-cell RNA-seq - Jmj KO, Utx KO, Tdt.Control

summary: Stem cells reside in specialized niches that play a critical role in modulating their fate. It remains unknown how MuSC adapt to the modified milieu to mediate muscle repair. Here, we show that the epigenetic enzyme JMJD3 coordinates MuSC adaptation to the regenerative niche in a non-cell autonomous manner where it modifies their extracellular matrix to integrate signaling that stimulates exit of quiescence. Genomics and transcriptomics approaches identified the hyaluronic acid (HA) synthesis enzyme Has2 as a key JMJD3 target gene that allows MuSCs to integrate signals from the regenerative niche.

overall_design: Single-cell RNA-Seq was performed on muscle satellite cells prepared from indicated mouse strains. Muscle satellite cells were isolated by FACS at 40 h post Cardiotoxin injury.

first: Kiran

last: Nakka

first: F


title: Defining the Transcriptional and Epigenetic Basis of Organotypic Endothelial Diversity in the Developing and Adult Mouse

status: Public on Jul 01 2022

city: Houston

first: Manuel

middle: Eliezer

last: Cantu Gutierrez

address: 1 Baylor Plaza

institute: Baylor College of Medicine

summary: The transport of gases, nutrients, metabolites and cells -  a prerequisite for proper organogenesis and tissue homeostasis - requires a functional circulatory system consisting of arteries and veins, separated by intervening capillary networks. Despite their shared origin and some common functions, endothelial cells (ECs), which line every blood vessel, display profound structural and functional heterogeneity unique to the organ and tissue that they reside in. The diversity of phenotypes that ECs can adopt suggest substantial plasticity and indicates that heterogeneity is a core endothelial property that allows ECs to fulfill their multiple tasks. While the anatomical heterogeneity of blood vessels across different organs has been appreciated for centuries, the molecular basis of the variation within the vertebrate vascular tree is poorly understood.   To decipher the transcriptional and epigenetic basis of endothelial heterogeneity across organs, and to determine how ECs mature during development, we surveyed the transcriptional and accessible chromatin landscape of ECs from the brain, retina, heart, liver, lung, and kidney of E12.5, P6, and adult mice. Through analysis of differential gene expression signatures, as well as chromatin accessibility, we have identified unique transcripts, as well as regulatory regions, that define each organ bed and developmental time point. Additionally, through single cell RNA-seq profiling of the embryonic and adult mouse we have determined that the endothelium of a single organ - in this case the brain - uses a diverse set of gene regulatory networks to mature and create a functional blood brain barrier.

overall_design:
Assay for Transposase-Accessible Chromatin with high-throughput sequencing (ATAC-seq) and RNA-seq of endothelial cells (Ecs) or input nuclei of trunk, heart and brain at embryonic day 12.5 and brain, retina, heart, lung, liver and kidney at postnatal day 6 and adult (2 month old) mice; single cell RNA-seq of ECs at embryonic day 9.5, 12.5, 16.5, postnatal day 8 and adult (2 month old) mouse brain.

UPDATE: [Apr-05-2026] The bigWig files for Samples GSM5611331 and GSM5611332 were replaced.

middle: E

first: Matthew

middle: C

last: Hill

first: Gabrielle

last: Largoza

first: James

middle: F

last: Martin

first: Joshua

middle: D

last: Wythe


title: The Atlas of Immune Infiltrates in Islet Cell Allo-transplantation

city: Shenzhen

first: Lisha

last: Mou

state: Guangdong

address: Room 604, Building 1, Yinxingzhijie 1 Qi Guanlan, Longhua District

institute: Shenzhen Second People's Hospital

summary: Islet transplantation to treat the late stage of T1DM patients has made some inspiring success recently in clinical trials. However, most of patients underwent a decline of islet cell graft in one to three years due to chronic immune rejection. Although the mechanisms of immune cells including macrophages, dendritic cells (DCs), neutrophils, natural killer cells (NKs), B cells, T cells that mediate immune rejection have been investigated, the overall characteristics of immune infiltrates in islet allografts remain unclear. Single-cell RNA sequencing (scRNA-seq) has provided us with new opportunities to study the molecular characteristics of the immune microenvironment in islet transplants. In the present study, we used scRNA-seq to comprehensively analyze the immune heterogeneity in islet graft, and compared the variances regarding to transcriptomal profiling and immune atlas between syngeneic islet transplantation and allograft.

overall_design:
We performed single-cell RNA sequencing (scRNA-seq) on islet cell allograft (Balb/c islets to C57bl/6 recipients) and syngeneic graft (C57bl/6 islets to C57bl/6 recipients) to identify the comprehensive cell components and variations that are related to graft rejection. 7 days after transplantation, the grafts were harvested and subjected to 10X Genomics pipeline barcoding, library preparation, and sequencing.

UPDATE: [Apr-05-2026] The titles and characteristics of Samples GSM5958320 and GSM5958321 were swapped. The processed data files for these Samples were renamed. The processed data files and raw data files associated with the GSM records did not change.

first: Pengfei

last: Chen

first: Ying

last: Lu

first: Yuanzheng

last: Peng


title: Histone methylation profiles of H3K4me3, H3K9me3, H3K36me3, H4K20me3, and RIOX2 in WT and mdig/mina53 KO MDA-MB 231 breast cancer cells

status: Public on Jul 12 2022

city: Stony Brook

first: Fei

state: New York

address: Lauterbur Drive Stony Brook, NY 11794

institute: Stony Brook Cancer Center

summary: The mineral dust-induced gene (mdig, also called as MINA or RIOX2) is overexpressed in breast cancer and its high expression correlates with poor overall survival of the patients. Our  studies suggested its role in cell motility, invasion and in the demethylation of DNA and histone proteins. Here we studied the global histone methylation profiles of human triple negative breast cancer cells MDA-MB-231 that were knocked out for mdig via CRISPR-Cas 9 gene editing. Altered histone methylation profiles impacted the transcriptional status of key genes implicated in cell growth, motility, invasion and cancer.

overall_design: Examination of 5 different histone modifications in WT and mdig KO MDA-MB 231 cells.

first: Chitra

last: Thakur

first: Qian

last: Zhang


title: Bulk RNA-Seq in JMJD3scKO, UTXscKO and Wild-type satellite cells

overall_design: RNA-Seq was performed on muscle satellite cells prepared from indicated mouse strains in duplicates. Muscle satellite cells were isolated by FACS at 30 h post Cardiotoxin injury.


title: Transcriptomic expression of A549 cells treated with palbociclib and indisulam or PF-06873600 and SUM159 cells treated with PF-06873600

status: Public on Mar 03 2022

city: Amsterdam

first: Rodrigo

last: Leite de Oliveira

address: De Boelelaan 1118

country: Netherlands

institute: Amsterdam UMC / location VUmc

summary: Inducing senescence in cancer cells is emerging as a new therapeutic strategy. We tested the senescence induction of palbociclib and indisulam or PF-06873600 in A549 and  PF-06873600 in SUM159 cells, and profiled these for senescence associated gene signatures.

overall_design: Transcriptomic analysis of A549 cells treated with palbociclib and indisulam or PF-06873600  and SUM159 cells treated with PF-06873600 and controls. The experiment was performed in technical duplicates. A549 cells were treated with 2µM Palbociclib,  0.5µM of indisulam and the combniation for 10 days. A549 and SUM159 were treated with 0.5µM PF-06873600  for 7 days.

first: Ziva

last: Pogacar

first: Jackie

last: Johnson

first: Lenno

last: Krenning

first: Fleur

last: Jochems

first: Giulia

last: DeConti

first: Cor

last: Lieftink

first: Arno

last: Velds

first: Leyma

last: Wardak

first: Kelvin

last: Groot

first: Arnout

last: Schepers

first: Liqin

last: Wang

first: Ji-Ying

last: Song

first: Marieke

last: vandeVen

first: Olaf

last: vanTellingen

first: Rene

middle: H

last: Medema

last: Bernards

last: LeitedeOliveira


title: Single-cell sequencing reveals homogeneity and heterogeneity in the molecular cytopathological mechanisms of AKI caused by different etiologies

status: Public on Apr 30 2022

city: Fuzhou

first: Zhimin

last: Chen

address: Chazhong Road NO.20

institute: the First Affiliated Hospital, Fujian Medical University, Fuzhou

summary: We constructed single-cell atlases of AKI induced by different etiologies, revealed potential homogeneity of injury patterns and heterogeneity between models in AKI. Extensive cell death and cytoskeletal remodeling events in proximal tubular cells (PTCs) as well as aberrant proliferation and inflammation of endothelial cells (ECs) in AKI are common injury patterns across different AKI models. However, there are differences in injury outcomes in PTCs with different etiologies, and ECs also have distinct transcriptional profiles.

overall_design:
Single-cell sequenceing of AKI induced by different etiologies:
cisplatin (CP), folic acid (FA), sodium oxalate (SO), ischemia reperfusion injury (IRI), and unilateral ureteral obstruction (UUO).

first: Yinshuang

last: Li

first: Ying

last: Yuan

first: Ruilong

last: Lan

first: Kunmei

last: Lai

first: Hong

first: Yanfang

last: Xu


title: Venetoclax cooperates with ionizing radiation to attenuate Diffuse Midline Glioma tumor growth

status: Public on Mar 23 2022

city: Aurora

first: Bridget

last: Sanford

state: CO

department: Pediatrics

institute: University of Colorado

summary: This article highlights the radiation induced cytotoxic effect of the BCL2 inhibitor, venetoclax, in diffuse midline gliomas (DMG). 1. RNA-seq: We performed bulk RNA sequencing of DMG cells exposed to 6Gy radiation and found the genes upregulated after radiation compared to unirradiated controls. 2. DNA Repair shRNA screen: We also performed a DNA Repair shRNA screen and identified the genes which are responsible for radioresistance in DMG.

overall_design: 1. RNA-seq samples were obtained from SF8628 DIPG cells radiated at 6Gy and unirradiated controls. 2. DNA Repair shRNA samples obtained from SF8628 cells transduced with DNA Repair shRNA pool and then either radiated at 6Gy or not radiated. Genomic DNA was collected at Day 21 after radiation.

first: Ilango

last: Balakrishnan

first: Rajeev

last: Vibhakar

first: Sujatha

last: Venkataraman


title: Transcriptomic expression of A549 and SUM159 cells treated with palbociclib and indisulam

first: Rodrigo

last: Leite de Oliveira

summary: Indisulam is a molecular glue targeting a splicing factor RBM39 for degradation. To assess splicing errors when treating the cells with indisulam, palbociclib and the combination we perform RNA sequencing and analyze splicing errors.

overall_design: Transcriptomic analysis of A549 ans SUM159 cells treated with palbociclib and indisulam and controls. The experiment was performed in technical duplicates. The cells were treated with 2µM Palbociclib, 3µM of indisulam and the combniation for 16h.

first: Ziva

last: Pogacar

first: Jackie

last: Johnson

first: Lenno

last: Krenning

first: Fleur

last: Jochems

first: Giulia

last: DeConti

first: Cor

last: Lieftink

first: Arno

last: Velds

first: Leyma

last: Wardak

first: Kelvin

last: Groot

first: Arnout

last: Schepers

last: Wang


title: Transcriptomic expression of SUM159 cells treated with palbociclib and indisulam

summary: Inducing senescence in cancer cells is emerging as a new therapeutic strategy. We tested the senescence induction of palbociclib and indisulam in SUM159 cells, and profiled these for senescence associated gene signatures.

overall_design: Transcriptomic analysis of  SUM159 cells treated with palbociclib and indisulam and controls. The experiment was performed in technical duplicates. The cells were treated with 2µM Palbociclib, 3µM of indisulam and the combniation for 16h.

first: Liqin

first: Ji-Ying

last: Song

first: Marieke

last: vandeVen

first: Olaf

last: vanTellingen

first: Rene

last: Medema

last: Bernards

last: LeitedeOliveira


title: HDAC3 Inhibition Causes the Impairment in Development of Neocortical VIP Interneurons via dysregulation of Notch Signaling and Autism-like Behaviors

status: Public on Jun 20 2022

city: Isehara

first: Takatoshi

last: Iijima

state: Kanagawa

address: 143 Shimokasuya

department: School of Medicine

country: Japan

institute: Tokai University

summary: Autism spectrum disorders (ASDs) are a neurodevelopmental disorder characterized by impairments in social interactions and stereotyped behaviors. While ASD has a strong genetic background, environmental factors including toxins, pesticides, infection and drugs are also known to confer autism susceptibility, likely by inducing epigenetic changes. Exposure to Valproic acid (VPA), a drug for epilepsy and bipolar disorders, during pregnancy is highly associated with the risk of ASD children. In rodents, in utero VPA exposure can precipitate behavioral phenotypes related to ASD in the offspring. Since VPA is an inhibitor of histone deacethytransferase (HDAC) activity, it thought to cause ASD with epigenetic modification. However, the core mechanism by which prenatal VPA exposure causes onset of ASD is still not fully uncovered.  Here we revealed that prenatal VPA exposure strongly influences development of vasoactive intestinal peptide (VIP) - positive neurons, a subtype of cortical GABAergic interneurons. The number of VIP+ interneurons was severely reduced in somatosensory area of VPA-exposed ASD animals. We then found that the reduction in VIP+ interneurons is caused by the inhibition of HDAC3 activity upon prenatal VPA exposure. Importantly, prenatal HDAC3 inhibition caused not only the selective reduction in VIP+ interneurons but also the ASD-like behaviors in mice. We then demonstrated that the HDAC3 inhibition aberrantly activates Notch signaling, which influences the cell fate determination of VIP+ interneuron progenitors in caudal ganglionic eminence. Thus, this study uncovers the mechanism by which specific HDAC inhibition during development influences a specific type of GABAergic interneurons in the ASD model. The findings provide a novel insight into the understanding of ASD pathophysiology.

overall_design: To explore the whole aspect of prenatal VPA exposure on neural development, we screened the gene alteration in the in vitro VPA model that mimics in utero VPA exposure by transcriptomic analyses.

first: Yoko

last: Hanno-Iijima

first: Moe

last: Nakanishi

first: Masami

last: Tanaka

first: Masayuki

first: Chisa

last: Okada

first: Goichi

last: Miyoshi

first: Toru

last: Takumi


title: Transcriptomic expression of A549 CDK2 KO cells treated or untreated with palbociclib

first: Rodrigo

last: Leite de Oliveira

summary: Inducing senescence in cancer cells is emerging as a new therapeutic strategy. We tested the senescence induction of palbociclib in CDK2 KO cells, and profiled these for senescence associated gene signatures. This was a CRISPR generated CDK2 KO clone in A549 cells.

overall_design: Transcriptomic analysis of A549 CDK2 KO cells treated with palbociclib and control. The experiment was performed in technical duplicates.

first: Ziva

last: Pogacar

first: Jackie

last: Johnson

first: Lenno

last: Krenning

first: Fleur

last: Jochems

first: Giulia

last: DeConti

first: Cor

last: Lieftink

first: Arno

last: Velds

last: Wardak


title: Senescence associated gene signatures


title: Identify key factors regulated by transcription factor Cebpd in the kidney during heart regeneration in zebrafish

status: Public on Feb 25 2022

first: Jianhong

last: Ou

state: Wisconsin

address: 330 N Orchard Street

institute: Morgridge Institute For Research

summary: In previous studies, we  identified and demonstrated that a 1.2kb cebpd downstream element (CEN) is capable and neccessary for the induction of cebpd in the kidney after cardiac injury. The goal of this study is to unveal the Cebpd regulated responses of kidney to cardiac regeneration in zebrafish. we profiled responses by kidney in cebpd mutant and enhancer (CEN) mutant fish zebrafish to massive injuries of the heart.

overall_design: cebpd+/+ and  cebpd-/-  kidney RNA-seq profiling after cardiac injury; CEN+/+ and  CEN-/-   kidney RNA-seq profiling after cardiac injury；

first: Fei

last: Sun

first: Kenneth

last: Poss


title: Nanostring nCounter Bovine Arrival BRD 60 Panel v1.0

status: Public on Mar 02 2022

first: Matthew

last: Scott

summary: The objective of this study was to corroborate the findings of previous BRD-associated transcriptome experiments, utilizing multiple independent populations of high-risk beef cattle.

overall_design: Blood samples were utilized from 240 cattle at facility arrival, across seven independent populations. Samples were randomly selected from cattle never having received clinical treatment for bovine respiratory disease (Healthy, n=116) and those having been treated at least one time in the 28 days post-arrival (BRD, n=124). BRD samples were further stratified into disease severity cohorts, based on frequency of treatment and mortality (Treated_1, n=91; Treated_2+, n=33). Samples were profiled for mRNA expression with the NanoString nCounter SPRINT Profiler, selecting 56 genes plus four internal controls. Quality control and differential expression was analyzed with nSolver v4.0. Six samples were removed from further analysis due to poor quality assessment and/or flagged normalization values.


title: Identification of enhancer elements that direct long-range responses to tissue injury

summary: The goal of this study is to unveal the responses of uninjured tissue to distant tissue injury and the structures required for long-range responses to tissue injuries. we profiled responses by the brain and kidney in zebrafish to massive injuries of the heart and identified cebpd transcript induction in both tissue. We also identified and demonstrated that a 1.2kb cebpd downstream element is capable and neccessary for the induction of cebpd in the brain after cardiac injury.

overall_design: Brain and kidney RNA-seq and ATAC-seq profiling after cardiac injury; cebpd+/+ and  cebpd-/-brain RNA-seq profiling after cardiac injury

first: Adam

last: Shoffner

first: Lingyun

last: Song

first: Alexis

last: Safi

first: Gregory

last: Crowford


title: miRNA overexpression modulates neutrophil migration

city: West Lafayette

first: Qing

last: Deng

state: Indiana

address: 915 W. State Street

department: Department of Biological Sciences

institute: Purdue University

summary: We performed RNAseq to identify miRNAs that were specifically down regulated in neutrophils, and RNAseq for identification of mRNA targets of  miRNA-31, miRNA-190 and miRNA-375  in neutrophils

overall_design: For miRNA target identification we sequenced messenger RNAs in zebrafish neutrophils over expressing miR-31, 190, 375 or vector control

first: Alan

middle: Y

last: Hsu

first: Sheng

last: Liu

first: Jun

last: Wan


title: Cotton transcriptome analysis reveals novel biological pathways that eliminate reactive oxygen species (ROS) under sodium bicarbonate (NaHCO3) alkaline stress

status: Public on Jan 26 2022

city: Zhengzhou

first: yanyong

last: cao

state: henan

address: No. 116, Huayuan Road

institute: Henan Academy of Agricultural Sciences

summary: To explore the mechanisms of cotton response to this alkaline stress, we used next-generation sequencing (NGS) technology to study transcriptional changes of cotton under NaHCO3 alkaline stress. A total of 18,230 and 11,177 differentially expressed genes (DEGs) were identified in cotton roots and leaves, respectively. Gene ontology (GO) analysis indicated the enrichment of DEGs involved in various stimuli or stress responses. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis showed that DEGs associated with plant hormone signal transduction, amino acid biosynthesis, and biosynthesis of secondary metabolites were regulated in response to the NaHCO3 stress. We further analyzed genes enriched in secondary metabolic pathways and found that secondary metabolites were regulated to eliminate the reactive oxygen species (ROS) and improve the cotton tolerance to the NaHCO3 stress. In this study, we learned that the toxic effect of NaHCO3 was more profound than that of NaOH at the same pH. Thus, Na+, HCO3- and pH had a great impact on the growth of cotton plant. The novel biological pathways and candidate genes for the cotton tolerance to NaHCO3 stress identified from the study would be useful in the genetic improvement of the alkaline tolerance in cotton.

overall_design: The transcriptional levels of cotton under two different alkaline stresses were tested

first: Yapeng

last: Fan

first: Wuwei

last: Ye


title: Single-cell transcriptomics of adult gd T-cell lineage commitment highlights its TCR-instructive nature

status: Public on Jan 01 2022

city: Marseille

first: Delphine

last: Potier

address: 27 boulevard Lei Roure

country: France

institute: CRCM

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

overall_design:
Refer to individual Series.

Additional scRNAseq R objects are available here:
https://doi.org/10.5281/zenodo.19002803


title: A primed immune transcriptional program is activated in oligodendroglia in multiple sclerosis [HiChIP]

status: Public on Jan 28 2022

city: Stockholm

first: Eneritz

last: Agirre

address: Solnavägen 9

department: MBB

country: Sweden

institute: Karolinska Institutet

summary: Multiple sclerosis (MS) is a disease characterized by a targeted immune attack on myelin in the central nervous system (CNS). We have previously shown that oligodendrocytes (OLs), myelin producing cells in the CNS, and their precursors (OPCs), acquire disease-specific transcriptional states in MS. To understand how these alternative transcriptional programs are activated in disease, we performed single-cell assay for transposase accessible chromatin using sequencing (scATAC-seq) on the OL lineage in the experimental autoimmune encephalomyelitis (EAE) mouse model of MS. We identified regulatory regions with increased accessibility in oligodendroglia (OLG) in EAE, some of which in the proximity of immune genes. A similar remodeling of chromatin accessibility was observed upon treatment of postnatal OPCs with interferon-gamma (IFNg), but not with dexamethasone. These changes in accessibility were not exclusive to distal enhancers, but also occurred at promoter regions, suggesting a role for promoters in mediating cell-state transitions. Notably, we found that a subset of immune genes already exhibited chromatin accessibility in OPCs ex vivo and in vivo, suggesting a primed chromatin state in OLG compatible with rapid transitions to an immune-competent state. Several primed genes presented bivalency of H3K4me3 and H3K27me3 at promoters in OPCs, with loss of H3K27me3 upon IFNg treatment. Inhibition of JMJD3/KDM6B, mediating removal of H3K27me3, led to the inability to activate these genes upon IFNg treatment. Importantly, OLGs from the adult human brain showed chromatin accessibility at immune gene loci, particularly at MHC-I pathway genes. A subset of single-nucleotide polymorphisms (SNPs) associated with MS susceptibility overlapped with these primed regulatory regions in OLG from both mouse and human CNS. Our data suggest that susceptibility for MS may involve activation of immune gene programs in OLG. These programs are under tight control at the chromatin level in OLG and may therefore constitute novel targets for immunological-based therapies for MS.

overall_design: We have performed H3K27ac-directed HiChIP in cultured primary mOPCs in control and IFNg treated conditions.

first: Mandy

last: Meijer

first: Mukund

last: Kabbe

first: Cassandra

last: van Tuijn

first: Abeer

last: Heskol

first: Ana

last: Falcao

first: M

last: Corces

first: Thomas

last: Montine

first: Xingqi

last: Chen

first: Howard

last: Chang

first: Gonçalo

last: Castelo-Branco


title: Ambient RNA analysis reveals misinterpreted and masked cell types in brain single-nuclei  datasets

status: Public on Oct 19 2022

first: Genevieve

last: Konopka

address: 650 Charles Young Drive South, 73-214 CHS

department: Neurobiology

institute: UCLA David Geffen School of Medicine

summary: Ambient RNA contamination in single-cell RNA sequencing (RNA-seq) is a significant problem, but its consequences are poorly understood. Here, we show that ambient RNAs in brain single-nuclei RNA-seq can have a nuclear or extra-nuclear origin, and each origin results in a distinct gene set signature. Both ambient RNA signatures are predominantly neuronal and we find that some previously annotated neuronal cell types are distinguished by ambient RNA. Strikingly, we also detect pervasive neuronal ambient RNA contamination in all glial cell types unless glia and neurons are physically separated prior to sequencing. We demonstrate that this contamination can be removed in silico using existing tools. We also show that previous annotations of immature oligodendrocytes are likely glial cells contaminated with ambient RNAs. After ambient RNA removal, we can detect extremely rare committed oligodendrocyte progenitor cells, which were infrequently annotated in previously published adult human brain datasets. Together, these results provide an in-depth analysis of ambient RNA contamination in brain single-cell datasets.

sample_organism:
Homo sapiens
Mus musculus

overall_design:
Data were reanalzyzed from raw fastq files with or without CellBender. Cells were annotated based on their cell type and glial cells were additionally annotated for ambient RNA contamination based on ambient RNA marker gene enrichment. Oligodendrocyte progenitor cells were additionally clustered and annotated.
---------------------------------------
Reanalyzed data includes PRJNA434002 (SRR9262927-SRR9262957), GSE192773, GSE97930, and GSE198640)

first: Emre

last: Caglayan

first: Yuxiang

last: Liu


title: HiCAR analysis of human embryonic stem cell differentiation reveals principles of cis-regulatory chromatin reorganization controlling developmental gene expression

status: Public on Feb 28 2022

first: Jianhong

last: Ou

summary: we report a novel method, Hi-C on Accessible Regulatory DNA (HiCAR), which leverages principles of ATAC-seq and high-throughput 3C-assay for genome-wide profiling of chromatin accessibility and open chromatin anchored cRE interactions.

overall_design: cross-linked cells were treated with Tn5 transposase that were assembled with an engineered DNA adaptor . The Tn5 adaptor contains a Mosaic End (ME) sequence for Tn5 recognition as well as a single-stranded flanking sequence that can be ligated to the CviQI-digested DNA fragment with a splint oligo. Next, restriction enzyme digestion was performed using the 4-base cutter CviQI, followed by in situ proximity ligation to ligate the Tn5 adaptor to the spatially proximal genomic DNA. After in situ ligation, cross-links were reversed, and the purified DNA was digested by another 4-base cutter NlaIII, followed by circularization and PCR amplification to generate HiCAR DNA libraries for Next-Generation-Sequencing (NGS)

first: Yarui

last: Diao

first: Xiaolin

last: Wei

first: Yu

last: Xiang


title: Single-cell transcriptomics of adult gd T-cell lineage commitment highlights its TCR-instructive nature II

first: Delphine

last: Potier

summary: Single cell RNA-seq study of T lymphocyte differentiation WT and LAT deficient mice in order to deciphy gd T-cell lineage commitment.

overall_design:
Single cell RNA-seq study of T lymphocyte differentiation. Two datasets were produced, corresponding to either double negative cells (DN, i.e. CD8– and CD4–) or total thymocytes (TOT) that were both sorted for live cells.

Additional scRNAseq R objects are available here:
https://doi.org/10.5281/zenodo.19002803

first: Sara

last: Scaramuzzino

first: Robin

last: Ordioni

first: Pierre

last: Grenot

first: Dominique

last: Payet-Bornet

first: Hervé

last: Luche

first: Bernard

last: Malissen


title: Single-cell transcriptomics of adult gd T-cell lineage commitment highlights its TCR-instructive nature I

overall_design:
Single-cell RNA-seq analysis of the T cell stages straddling the developmental bifurcation leading to αβ and γδ T cells in adult thymus. Thymocyte subsets encompassing such bifurcation were isolated from 6- to 8-week-old mice using established cell surface markers and subjected to single cell RNA sequencing. Double negative cells (DN, i.e. CD8– and CD4–) cells were sorted into 5 subsets corresponding to DN3a bi-potent αβ/γδ precursors which rearrange the genes coding for the TCRγ, TCRδ, and TCRβ chains, post-selected αβ precursors (DN3b TCRγδ– and DN4 TCRγδ–; in short DN3b γδ– and DN4 γδ–), post-selected γδ precursors (DN3b TCRγδ+; in short DN3b γδ+), and immature γδ T cells in the process of functional diversification (DN4 TCRγδ+; in short DN4 γδ+). In addition, to precise the role of γδ TCR signals in the earliest phases of γδ lineage commitment and specification two subsets of DN3 cells expressing signaling-defective γδ TCR from TCRd-H2BEGFP Lat-deficient mice were isolated : DN3 γδint and DN3 γδ–.
Each subset was spike-in using 500 splenic B cells in order to check dataset merging quality.

Additional scRNAseq R objects are available here:
https://doi.org/10.5281/zenodo.19002803


title: A primed immune transcriptional program is activated in oligodendroglia in multiple sclerosis [Cut&Run IFNgvsCtr]

first: Eneritz

last: Agirre

overall_design: We have performed bulk CUT&RUN for H3K27ac, H3K27me3, H3K4me3 and Ctcf from FACS sorted Sox10GFP+ oligodendrocyte precursor cells  treated with IFN-gamma fro 48 hours.

first: Mandy

last: Meijer


title: MYC assembles and stimulates topoisomerases 1 & 2 in a “topisome” [CAD-seq]

status: Public on Dec 09 2021

city: Solna

first: Vladislav

last: Kuzin

state: Stockholm

department: Cell and Molecular Biology

institute: Karolinska Institute

summary: High-intensity transcription and replication supercoil DNA to levels that can impede or halt these processes. As a potent transcription amplifier and replication accelerator, the proto-oncogene MYC must somehow manage these high levels of torsional stress. By comparing gene expression with the recruitment of topoisomerases and MYC to promoters, we surmised a direct association of MYC with Topoisomerases 1 (TOP1) and 2A (TOP2A) that was confirmed in vitro and in vivo. Beyond recruiting topoisomerases, MYC directly stimulates their activities in vitro and in vivo. We identify a MYC-nucleated “topoisome” complex that unites and increases the levels of both  both TOP1 and TOP2, as well as their activities at promoters and enhancers. Whether TOP2A or TOP2B is included in the topoisome, is dictated by the presence of c-MYC or MYCN, respectively. Thus, in vivo and in vitro, MYC assembles tools that simplify DNA topology and promote genome function under high output conditions.

overall_design:
To probe binding profiles of TOP2A, MYC and RNAPII chromatin immunoprecipitation sequencing (ChIP-seq) experiments were perfromed. ChIP-seq of TOP2A in TOP2A-FLAG HCT116 and MYC in asynchronous wild type HCT116 cells and ChIP-seq of MYC and RNAPII in asynchronous TOP1/TOP2A auxin inducible degron HCT116 cells (-mAID). For mapping of topoisomerase activity we designed CAD-seq method which enables mapping of topoisomerase cleavage complexes. TOP1cc CAD-seq was performed in K562 MYC-mAID cells. To pull down the "topisome" complex we designed cross CAD-seq method which involves trapping of TOP2A by etoposide treatment and then proceeding with a pull down against TOP1. TOP1cc cross-CAD-seq was performed in U2OS cell with and without MYC induction to look at the formation of the topisome.
Please note that the processed data generated from both replicates is linked to the corresponding rep1 sample records.

first: Subhendu

middle: K

last: Das

first: Donald

last: Cameron

first: Suzanne

last: Sanford

first: Rajiv

last: Jha

first: Zuqin

last: Nie

first: Marta

middle: T

last: Rosello

first: Jan

last: Wisniewski

first: David

last: Price

first: Brian

last: Lewis

first: Fedor

last: Kouzine

last: Levens

first: Laura

last: Baranello


title: MYC assembles and stimulates topoisomerases 1 & 2 in a “topisome”

overall_design: Refer to individual Series


title: MYC assembles and stimulates topoisomerases 1 & 2 in a “topisome” [cross-CAD-seq]


title: Shank3(∆C/+) mice exhibit altered transcriptomic response to swim stress

status: Public on Nov 18 2021

city: Baltimore

first: Lisa

middle: Nicole

last: Learman

state: MD

address: 725 N. Wolfe St., PCTB 917

department: Neuroscience

institute: Johns Hopkins University School of Medicine

summary: Shank3 is a postsynaptic protein that complexes with group 1 metabotropic, AMPA-, and NMDA-type glutamate receptors. Mutations of Shank3 are causal for Phelan-McDermid syndrome (PMS) and associated autism phenotypes. Individuals with PMS often exhibit sensitivity to novelty or stress that can result in behavioral deterioration. Here we use a Shank3 mouse model with face-validity to PMS [Shank(3∆C/+)] and perform a transcriptomic analysis of principal neurons from neocortex of mice subjected to brief swim stress.  Analysis reveals overrepresented pathways related to synapses accompanied by elevated expression of the immediate early gene Homer1a. In normal brain Homer1a is dynamically expressed in association with motivated behavior and mediates an essential step in sleep-related homeostatic down-scaling of synaptic proteins. This is consistent with observations that synaptic Shank3 expression requires Homer cross-linking, which is interrupted by Homer1a.  Accentuated Homer 1a expression in Shank3(∆C/+) results in marked reductions of Shank3 expression, changes in synapse composition and NMDA-dependent synaptic plasticity, and disruption of social motivation. Deletion of Homer1a partially mitigates stress-induced phenotypes in Shank3(∆C/+) mice. Homer 1a is required for developmental plasticity, learning and memory, yet its enhanced expression in Shank3(∆C/+) may underlie a vulnerability of PMS patients that highlights the challenge of clinical management.

overall_design: Pyramidal Neuron mRNA profiles of Shank3(+/+) and Shank3(∆C/+) mice on C57BL6 strain background with and without swim stress

first: Raozhou

last: Lin

middle: N

first: M

last: Bangash

first: Tatiana

last: Melnikova

first: Erica

last: Leyder

first: Nirinjini

last: Naidoo

last: Linden

first: Joo

last: Park

first: Alena

last: Savonenko

first: Paul

last: Worley


title: Multipopulational transcriptome analysis of beef cattle at arrival to identify and further validate candidate biomarkers for predicting clinical bovine respiratory disease

status: Public on Dec 13 2021

city: Canyon

first: Matthew

last: Scott

address: 3201 Russell Long Blvd

institute: Texas A&M University

summary:
Objective: Classify and further validate BRD-associated genes and mechanisms found to be differentially expressed at facility arrival in post-weaned beef cattle from multiple independent populations. Our approach was to profile and compare at-arrival whole blood transcriptomes of post-weaned beef cattle that failed to develop symptoms associated with clinical BRD and cattle that ultimately were diagnosed and treated for clinical BRD within the first 28 days of facility arrival, further stratifying diseased animals into severity cohorts.
Methods: Whole blood RNA profiles were generated via NGS approach, using an Illumina Novaseq 6000. Individual samples were processed using an adaptation of the Revised Tuxedo Suite protocol (Tuxedo 2), then analyzed in R using edgeR with likelihood-ratio testing. Genes were considered differentially expressed with an FDR cutoff of 0.05. Downstream analysis involved PCA, gene ontology term enrichment, pathway analysis, protein-protein interaction networking, and IPA.
Results: 132 differentially expressed genes were identified between all three cohorts. Biological processes and pathways primarily involved neutrophilic activity, antimicrobial killing, cell cornification, and inflammatory signaling/regulation.
Conlusions: This study corroborated genes and pathways identified in our previous work, while providing novel genes and pathways for future analysis.

overall_design:
48 whole blood mRNA samples of stocker cattle at facility arrival were sequenced with an Illumina Novaseq 6000.
Disease severity cohorts:
"Healthy" animals never showed clinical signs throughout the course of that year's study.
"Treated_1" showed clinical signs after arrival and were only treated with injectable antimicrobials.
"Treated_2+" showed clinical signs after arrival and were treated more than one time with injectable antimicrobials and/or were euthanized due to clinical decline.
The antimicrobials used to treat clinical respiratory disease were florfenicol, ceftiofur, and enrofloxacin.


title: Titanium with nanotopography attenuates the osteoclast-induced disruption of osteoblast differentiation by regulating histone methylation

status: Public on Nov 23 2021

city: Ribeirão Preto

first: Rayana

middle: Longo

last: Bighetti-Trevisan

state: São Paulo

address: Avenida do Café s/n.

department: Basic and Oral Biology

country: Brazil

institute: University of São Paulo

summary:
We report the application of RNA sequencing to evaluate the effect of titanium (Ti) with nanotopography, compared to Ti control, on the whole transcriptome of osteoblastic cells in isolated cultures grown on these surfaces and to evaluate the effect of Ti with nanotopography, compared to Ti control, on the whole transcriptome of osteoblastic cells, grown on these surfaces, in co-culture with osteoclastic cells.
MC3T3-E1 osteoblastic cells were plated at the density of 1x10^4 cells/well on the Ti discs with nanotopography and Ti control, in 24-well plates in osteogenic medium and kept isolated for 5 days to allow cell adhesion. Osteoclast cells from the RAW 264.7 lineage were cultured on osteoclastogenic medium on ThinCert™ cell culture inserts (Greiner Bio-One), with 0.4 μm pore, at the density of 1x104 cells/membrane, and was also be kept isolated for 5 days to allow cell adhesion. At the end of this period theThinCert™ cell culture inserts (Greiner Bio-One), containing the osteoclast cells were positioned on the osteoblastic cell cultures, thereby establishing indirect co-culture. The controls were osteoblastic cells of the MC3T3-E1 lineage grown on the Ti discs in the absence of osteoclast cells of the RAW 264.7 lineage, i.e., not maintained in co-culture.

overall_design: All the experiments were performed considering biological triplicates of each group.

first: Luciana

middle: O

last: Almeida

first: Larissa

last: Castro-Raucci

first: Jonathan

last: Gordon

first: Coralee

last: Tye

first: Gary

middle: S

last: Stein

first: Jane

middle: B

last: Lian

first: Janet

first: Adalberto

last: Rosa

first: Marcio

last: Beloti


title: MYC assembles and stimulates topoisomerases 1 & 2 in a “topisome” [ChIP-seq]

first: Vladislav

last: Kuzin

first: Subhendu

last: Das

first: Donald

last: Cameron

first: Suzanne

last: Sanford

first: Rajiv

last: Jha

first: Zuqin

last: Nie

first: Marta

last: Rosello

first: Jan

last: Wisniewski

first: David

last: Price

first: Brian

middle: A

last: Lewis

first: Fedor

last: Kouzine

last: Levens

first: Laura

last: Baranello


title: High-resolution transciptome mapping and N6-methyladenosine modification mapping of RAW264.7 cell lines treated with TCP, TBP or TIP.

status: Public on Jul 01 2021

city: nanjing

first: Zhou

last: Jun

state: jiangsu

address: longmiandadao

department: College of life science and technology

institute: China Pharmaceutical University

summary:
Purpose:Detect transcriptome-wide mapping of m6A modifications by MeRIP-seq between normal and chemical-treated RAW264.7 cells.
Methods:Total RNA was extracted using TRIzol Reagent followed by chemical fragmentation.  The fragmented RNA was incubated with anti-m6A antibody. The desired m6A-enriched RNA eluate was used to construct cDNA library in parallel with input control.
Conclusion: Our study revealed the difference of m6A-methylated RNA between normal and TCP/TBP/TIP-treated cells by RNA-seq and MeRIP-seq technologies.

overall_design: Compare the difference of m6A-methyalated RNA between normal and TBP/TCP/TIP treated samples.

first: Linyuan

last: Huang

first: Jun

last: Zhang


title: Cellular and transcriptional immune responses induced by neoadjuvant PD-1 blockade in glioblastoma patients

status: Public on Oct 18 2021

city: Los Angeles

first: Willy

last: Hugo

state: California

address: 10833 Le Conte Ave

department: Medicine

institute: University of California, Los Angeles

summary: The differentiation and effector function of tumor infiltrating lymphocytes and macrophages in the tumor microenvironment is critical for productive anti-tumor immune responses, although direct evidence for this remains poorly characterized in brain cancer patients.  Using mass cytometry, single-cell RNA sequencing, and quantitative multiplex immunofluorescence, we comprehensively characterized the phenotype and single-cell transcriptome of myeloid cells and T lymphocytes that infiltrated malignant gliomas, and identified how such populations changed following neoadjuvant PD-1 checkpoint blockade in recurrent glioblastoma patients.  Cells of the myelo-monocytic lineage represented approximately three quarters of the immune cell infiltrate, with T lymphocytes representing the next major immune cell subset by density and percentage, but following neoadjuvant PD-1 antibody blockade, the ratio of myeloid cells to T cells significantly decreased.  We then used single-cell RNA sequencing to comprehensively define the transcriptional profiles of lymphoid and myeloid populations in these tumors.  Recurrent GBM patients treated with neoadjuvant PD-1 checkpoint inhibition possessed a greater fraction of CD8+ T cells with an effector T cell transcriptional program. The increased effector T cell populations were associated with the distinct upregulation of the chemokines, CXCL9 and CXCL10 by an interferon-responsive macrophage cluster.  Importantly, we also identified that neoadjuvant PD-1 blockade was associated with significantly increased cellular interactions specifically between CD8+ T cells and tumor associated macrophages within the tumor microenvironment. Together, these findings suggest that effector T cell infiltration and differentiation are increased with neoadjuvant PD-1 blockade but impeded by adaptive resistance and immunosuppression from tumor associated macrophages.  Future therapeutic strategies to target this dominant immunosuppressive myeloid cell population may be needed to achieve true, therapeutic interventions in this patient population.

overall_design: This dataset contains a total of 40 single cell transcriptomes of new and recurrent glioblastoma with/without neoadjuvant anti-PD1 treatment.

first: Alexander

last: Lee

first: Lu

last: Sun

first: Aaron

last: Mochizuki

first: Jeremy

middle: G

last: Reynoso

first: Joey

middle: R

last: Orpilla

first: Frances

last: Chow

first: Jenny

last: Kienzler

first: Richard

last: Everson

last: Nathanson

first: Steven

last: Bensinger

first: Linda

middle: M

last: Liau

first: Timothy

last: Cloughesy

first: Robert

last: Prins


title: Overexpression of the cytokinesis regulator PRC1 activates the p53 pathway due to cytoplasmic microtubule-bundling resulting in senescence of A549 lung cancer cells

status: Public on Sep 01 2021

city: Wuerzburg

first: Carsten

middle: P

last: Ade

address: Am Hubland

department: Lehrstuhl Biochemie und Molekularbiologie

country: Germany

institute: University of Wuerzburg

summary: Protein regulator of cytokinesis 1 (PRC1) is a microtubule-bundling protein with essential roles in mitosis and cytokinesis. In this study we investigated the potential nuclear functions of PRC1 and the consequences of overexpression of PRC1 by using lung cancer cell lines stably expressing inducible expression constructs for PRC1. Ectopically expressed PRC1 resulted in proliferation defects, multi-nucleation and enlargement of cells which were directly linked to microtubule-bundling within the cytoplasm. Genome wide expression profiling by RNA sequencing revealed that the p53 pathway is activated upon overexpression of PRC1 resulting in cellular senescence. A mutant of PRC1 unable to enter into the nucleus induced the same gene sets as wildtype PRC1, suggesting that PRC1 has no nuclear-specific functions in lung cancer cells. The depletion of p53 switched the response to PRC1 overexpression or depletion from senescence to apoptosis. In addition, treatment with cisplatin, a commonly used chemotherapeutic drug, enhanced the proliferation defects due to deregulated PRC1, implicating PRC1 as a possible therapeutic target for cancer. Taken together, PRC1 needs to be tightly regulated to allow unperturbed proliferation of lung cancer cells.

overall_design: RNA-seq analysis of A549 lung cancer cells after overexpression of PRC1 or PRC1-NLS3A.

first: Steffen

last: Hanselmann

first: Woo

middle: J

last: Shin

first: Stefan

last: Gaubatz


title: Epithelial membrane protein-2 promotes VEGF signaling to promote pathological neovascular growth in retinopathy of prematurity

status: Public on Dec 17 2021

city: LA

first: Madhuri

last: Wadehra

address: 675 Charles Young Dr. South/ 4726 MRL

department: Pathology and Lab Medicine

institute: UCLA

summary: Retinopathy of prematurity (ROP) is a leading cause of childhood blindness, and exclusively affects infants born prematurely. In this study, we test the hypothesis that EMP2 contributes to neovascularization in a mouse model of the disease.  We show that EMP2 promotes neuronal VEGF signaling and that its downregulation reduces severity of neovascularization.

overall_design: RNA-Seq was performed on RNA from frozen retinal tissues. Four replicates from the following conditions were profild: WT normoxia, EMP2 KO normoxia, WT hyperoxia, and EMP2 KO hyperoxia group at P17.

first: Michel

first: David

last: Casero

first: Brian

last: Aguirre

first: Lynn

last: Gordon

first: Alison

last: Chu


title: Bioplatforms Australia: Antibiotic Resistant Sepsis Pathogens Framework Initiative - Staphylococcus aureus BPH2947

city: Sydney

last: Bioplatforms Australia

state: NSW

address: Level 4, Building 4WW, Research Park Drive, Macquarie University

institute: Bioplatforms Australia

summary: The Antibiotic Resistant Sepsis Pathogens Framework Initiative aims to develop a framework dataset of 5 sepsis pathogens (5 strains each) using an integrated application of genomic, transcriptomic, metabolomic and proteomic  technologies. The pathogens included in this initiative are: Escherichia coli, Klebsiella pneumoniae complex, Staphylococcus aureus, Streptococcus pyogenes, and Streptococcus pneumoniae. This submission pertains to strain BPH2947.

overall_design:
12 samples, 2 conditions, 6 biological replicates per condition.
contributor: Bioplatforms Australia Antibiotic Resistant Sepsis Pathogens Framework Initiative


title: Bioplatforms Australia: Antibiotic Resistant Sepsis Pathogens Framework Initiative - Staphylococcus aureus BPH2900

summary: The Antibiotic Resistant Sepsis Pathogens Framework Initiative aims to develop a framework dataset of 5 sepsis pathogens (5 strains each) using an integrated application of genomic, transcriptomic, metabolomic and proteomic  technologies. The pathogens included in this initiative are: Escherichia coli, Klebsiella pneumoniae complex, Staphylococcus aureus, Streptococcus pyogenes, and Streptococcus pneumoniae. This submission pertains to strain BPH2900.

overall_design:
11 samples, 2 conditions, 5-6 biological replicates per condition.
contributor: Bioplatforms Australia Antibiotic Resistant Sepsis Pathogens Framework Initiative


title: Bioplatforms Australia: Antibiotic Resistant Sepsis Pathogens Framework Initiative - Staphylococcus aureus BPH2986

summary: The Antibiotic Resistant Sepsis Pathogens Framework Initiative aims to develop a framework dataset of 5 sepsis pathogens (5 strains each) using an integrated application of genomic, transcriptomic, metabolomic and proteomic  technologies. The pathogens included in this initiative are: Escherichia coli, Klebsiella pneumoniae complex, Staphylococcus aureus, Streptococcus pyogenes, and Streptococcus pneumoniae. This submission pertains to strain BPH2986.


title: Bioplatforms Australia: Antibiotic Resistant Sepsis Pathogens Framework Initiative - Staphylococcus aureus BPH2819

summary: The Antibiotic Resistant Sepsis Pathogens Framework Initiative aims to develop a framework dataset of 5 sepsis pathogens (5 strains each) using an integrated application of genomic, transcriptomic, metabolomic and proteomic  technologies. The pathogens included in this initiative are: Escherichia coli, Klebsiella pneumoniae complex, Staphylococcus aureus, Streptococcus pyogenes, and Streptococcus pneumoniae. This submission pertains to strain BPH2819.


title: mRNA-seq of PTC-028 treated fusion-positive rhabdomyosarcoma cells

status: Public on Jun 11 2021

city: Atlanta

first: Karmella

last: Haynes

state: GA

address: 1760 Haygood Dr NE

department: Wallace H. Coulter Department of Biomedical Engineering

institute: Emory University

summary:
Purpose: This study aims to identify novel targets in the rare pediatric cancer, fusion-positive rhabdomyosarcoma (FP-RMS), and examine differences/similarities in FP-RMS tumor responses to BMI1 (B lymphoma Mo-MLV insert region 1 homolog) inhibition.
Methods: FP-RMS cell lines Rh28 and Rh30 were treated with DMSO (vehicle) or PTC-028, a BMI1 inhibitor, and RNA was collected after 24 or 48 hr in triplicate. RNA-seq was performed, and gene expression data were analyzed through Gene Ontology (GO) and KEGG (Kyoto Encyclopedia of Genes and Genomes) pathway analyses. Data from OncoPPi and the STRING database were also utilized in this study.
Results: Both Rh28 and Rh30 had some overlapping pathways affected by PTC-028, notably downregulation of cell cycle progression, the DNA damage response, and cholesterol biosynthesis. Rh30+PTC-028 had more genes containing TEAD-motifs downregulated compared to Rh28+PTC-028. Rh28 and Rh30 also had differing changes in expression in kinases of LATS1/2, EPHA2, and PDGFRA.
Conclusion: Overall, these results bring new insights into pathways influenced by BMI1 expression and contrasting intertumor drug responses in FP-RMS.

overall_design: Fusion-positive rhabdomyosarcoma cell lines (Rh28 and Rh30) were treated with either DMSO (24 hr) or PTC-028 (24 hr or 48 hr).  Total RNA was extracted from DMSO and PTC-028 treated cells. Cells were analyzed by RNA-seq in triplicate.

first: Cara

middle: E

last: Shields

middle: W

last: Schnepp


title: Characterization of the transcriptomic profile of Plagl1+/-pat retina

status: Public on May 06 2021

city: Lethbridge

first: Yaroslav

last: Ilnytskyy

state: AB

address: 4401, University Drive W

department: Biology

country: Canada

institute: University of Lethbridge

summary: Retinal damage triggers reactive gliosis in Müller glia across vertebrate species, but only in regenerative animals, such as teleost fish, do Müller glia initiate repair; proliferating and undergoing neurogenesis to replace lost cells. We found that Plagl1, a maternally imprinted gene, is dynamically regulated in reactive Müller glia post-insult, with transcript levels transiently increasing before stably declining. To study Plagl1 retinal function, we examined Plagl1+/-pat null mutants postnatally, revealing defects in retinal architecture, visual signal processing and a reactive gliotic phenotype. Plagl1+/-pat Müller glia proliferate ectopically and give rise to inner retinal neurons and photoreceptors. Transcriptomic and ATAC-seq profiles revealed similarities between Plagl1+/-pat retinas and neurodegenerative and injury models, including an upregulation of pro-gliogenic and pro-proliferative pathways, such as Notch, not observed in wild-type retinas Plagl1 is thus an essential component of the transcriptional regulatory networks that retain mammalian Müller glia in quiescence.

overall_design: Transcriptomic prolifing of post-natal (P)7 Plagl1 Knock-out (8 biological samples) and 4 wild-type (4 biological samples) retinas

first: Yacine

last: Touahri

first: Igor

last: Kovalchuk

first: Carol

last: Schuurmans


title: Lung and primary pulmonary endothelial single cell RNA seq data

status: Public on May 26 2021

city: Hannover

first: Jonas

last: Schupp

address: Carl-Neuberg-Str. 1

department: Respiratory Medicine

institute: Hannover Medical School

summary: Single Cell RNAseq of Whole Lung Dissociates from control lungs and primary pulmonary endothelial cells

overall_design:
Exploratory analysis of healthy lung cell populations and of primary pulmonary endothelial cells
Raw data for samples GSM5020379-GSM5020382 not provided due to patient privacy concerns.

first: Naftali

last: Kaminski

first: Ivan

last: Rosa

middle: C

first: Taylor

last: Adams

first: Laura

last: Niklason

first: Richard

last: Pierce

first: Yifan

last: Yuan


title: Characterization of the chromatin accessibility profile of Plagl1+/-pat retina

status: Public on May 05 2021

overall_design: ATAC-seq of post-natal (P)7 Plagl1 Knock-out (3 biological samples) and wild-type (3 biological samples) retinas


title: RNA/WES/ATAC/scRNA sequencing of murine melanoma primary and LN metastases

status: Public on Jun 14 2021

city: Palo Alto

first: Nathan

middle: Edward

last: Reticker-Flynn

state: CA

address: 3373 Hillview Ave

department: Pathology

institute: Stanford University

summary: The purpose of this study is to identify transcriptional, mutational, andepigenetic differences between LN metastases from primary tumors. Using in vivo serial passaging of the minimally metastatic syngeneic murine melanoma cell line B16-F0, we have generated nearly 300 unique cell lines spanning nine generations of in vivo passaging, derived from LNs, and exhibiting varying degrees of metastatic potential to LNs. Here, we perform mRNAseq on 30 of the lines representing a range of anatomical locations (distinct LNs), generations, and phylogenetic lineages. The subsequent differential expression analysis reveals a marked upregulation of immune-related genes. Additionally, we perform WES to identify differences in particular mutations, total mutational burden, and predicted neoantigen burden. Additionally, we perform ATAC-seq to assess changes in chromatin accessibility hat correlate with LN metastasis. We also perform scRNA-seq on dissociated LNs from mice with and without LN metastases.

overall_design:
mRNA profiles were generated from 30 cell lines derived from the various LN lines and parental. The parental was sequenced in triplicate where each replicate was harvested at distinct passage numbers to account for variability in the profile due to culture. Samples were sequenced on an Illumina HiSeq 2500 to a depth of 50M reads. Following quality filtering, transcript abundance was quantified using Salmon and differential gene expression analysis was performed using DESeq2. LN lines from later generations were compared to the parental or early generation lines.

For WES, 10 cell lines were analyzed. These data are accessible directly from SRA at Accession PRJNA820881.
For ATAC-seq, 3 samples each from parental, LN3, and LN7 generations were analyzed.
For scRNAseq, a LN from tumor naive, parental (non-metastatic) tumor, and LN6 (LN-metastatic) tumor mice each were analyzed.

first: Edgar

last: Engleman


title: Transcriptome-wide N6-methyladenosine modification profiling of long non-coding RNAs and circular RNA during growth of Marek’s disease virus in vitro

status: Public on Apr 28 2021

first: ZHU Xiaojing

middle: Xiaojing

last: ZHU

state: Henan

address: 15 Longzihu University Park, Zhengdong New District

institute: Henan Agricultural University

summary: we profiled the transcriptome-wide m6A modification in lncRNAs and circRNA in MDV-infected chicken embryo fibroblast (CEF) cells. Methylated RNA immunoprecipitation sequencing results revealed that the lncRNA m6A modification is highly conserved with MDV infection increasing the expression of lncRNA m6A modified sites compared to uninfected cell controls. m6A modification was highly conserved in circRNAs. Comparing to the uninfected group, the number of peaks, conserved motifs, and abundance of circRNA m6A modification, was not significantly different in cells that were infected with MDV. Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes pathway (KEGG) analysis revealed that lncRNA m6A modifications were highly associated with signaling pathways associated with MDV infection. The alterations seen in transcriptome-wide m6A occurring in lncRNAs following MDV-infection suggest this process plays important regulatory roles during MDV replication.  And the insulin signaling pathway was associated with the regulation of m6A modified circRNAs in MDV infection. In summary, we report for the first time profiling of the alterations in transcriptome-wide m6A modification in lncRNAs and circRNA of MDV-infected CEF cells.

overall_design: Examing 2 conditions, each with 3 replicates

first: Guoqing

last: Zhuang

first: Aijun

last: Sun


title: Gene expression analysis of Nrg1 stimulated zebrafish hearts  [mRNA]

status: Public on Apr 14 2021

city: Madison

first: Jianhong

last: Ou

address: 330 N Orchard Street

institute: Morgridge Institute For Research

summary: We report high-throughput profiling of gene expression from whole zebrafish ventricles. We profile mRNA in uninjured ventricles and those undergoing 7 days of cardiomyocyte hyperplasia after genetic stimulation of Nrg1. This study provides a framework for understanding transcriptional changes during adult models of regeneration.

overall_design: Examination of gene expression in cardiomyocytes under different states of proliferation.

first: M

middle: I

last: Pronobis

first: S

last: Zheng

last: Singh

first: J

last: Goldman

first: K

middle: D

last: Poss


title: Bioplatforms Australia: Antibiotic Resistant Sepsis Pathogens Framework Initiative - Staphylococcus aureus BPH2760

last: Bioplatforms Australia

summary: The Antibiotic Resistant Sepsis Pathogens Framework Initiative aims to develop a framework dataset of 5 sepsis pathogens (5 strains each) using an integrated application of genomic, transcriptomic, metabolomic and proteomic  technologies. The pathogens included in this initiative are: Escherichia coli, Klebsiella pneumoniae complex, Staphylococcus aureus, Streptococcus pyogenes, and Streptococcus pneumoniae. This submission pertains to strain BPH2760.


title: Transcriptome Signature Post Reovirus Treatment In KRAS Mutated Colorectal Cancer

status: Public on May 01 2021

city: Bronx

first: RADHASHREE

last: MAITRA

state: NY

address: 1300 Morris Park Ave

department: Medicine (Oncology)

institute: Albert Einstein College of Medicine of Yeshiva University

summary: Reovirus propagates with high efficiency in KRAS mutated colorectal cancer (CRC). About 45-50% of CRC patients possess KRAS mutation. Oncolytic reovirus treatment in combination with chemotherapy was tested in patient samples possessing KRAS mutated metastatic CRC. This is the raw data from the peripheral mononuclear cell (PBMC) samples at 4 timepoints (pre treatment, 48 hours, day 8, and day 15).

overall_design: Reovirus was administered as a 60-min intravenous infusion for 5 consecutive days every 28 days, at tissue culture infective dose (TCID50) of 3X1010. Peripheral blood mononuclear cells (PBMC) were isolated from whole blood pre and post reovirus administration at 48hr, Day-8, and Day-15. Clariom_D_Human_Assay was used to determine the overall gene expression compared to pre-reovirus treatment by RNA sequencing.

first: Radhashree

last: Maitra

first: Sanjay

last: Goel

first: Elisha

last: Fogel


title: Negative Elongation Factor (NELF) regulates muscle progenitor expansion for efficient myofiber repair and stem cell pool repopulation [NelfE_Cut&Tag]

status: Public on Mar 18 2021

first: Jeffrey

last: Dilworth

state: WI

address: 1111 Highland Ave - WIMR II 4518

department: Cell and Regenerative Biology

institute: University of Wisconsin - Madison

summary: Negative Elongation Factor (NELF) is a critical transcriptional regulator that works through stabilizing paused RNA Polymerase to permit rapid gene expression changes in response to environmental cues. Whilst NELF is essential for embryonic development, its role in adult stem cells remains unclear. Here, through a muscle stem cell-specific deletion, we show that NELF is required for efficient muscle regeneration and replenishing the stem cell pool. Mechanistic studies using PRO-seq, single cell trajectory analyses and myofiber cultures revealed that NELF works at a specific stage of muscle regeneration whereby it mediates massive expansion of muscle progenitors. Strikingly, transplantation experiments indicate that these progenitors are also necessary for stem cell pool repopulation implying they are able to return to quiescence. Thus, we identified a critical role for NELF in expansion of muscle progenitors in response to injury and revealed that progenitors returning to quiescence are major contributors to stem cell pool repopulation.

overall_design: Myoblasts were isolated from Wildtype (WT) and NELF-BscKO (KO) mice in biological triplicate, and expanded in vitro. Ex vivo knockout was induced with 4-hydroxy-tamoxifen over 72 hours, and the resulting populations used for sample preparation

first: Daniel

last: Robinson

first: Morten

last: Ritso

first: Geoffrey

last: Nelson

first: F


title: Negative Elongation Factor (NELF) regulates muscle progenitor expansion for efficient myofiber repair and stem cell pool repopulation [S5_RNApolII_Cut&Tag]


title: A primed immune transcriptional program is activated in oligodendroglia in multiple sclerosis

status: Public on May 21 2021

first: Eneritz

last: Agirre

address: Solnavägen 9

institute: Karolinska Institutet

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

platform_organism:
Homo sapiens
Mus musculus

overall_design: Refer to individual Series


title: Negative Elongation Factor (NELF) regulates muscle progenitor expansion for efficient myofiber repair and stem cell pool repopulation {ChIP-seq]

summary: Negative elongation factor (NELF) is a critical transcriptional regulator that stabilizes paused RNA polymerase to permit rapid gene expression changes in response to environmental cues. Although NELF is essential for embryonic development, its role in adult stem cells remains unclear. In this study, through a muscle-stem-cell-specific deletion, we showed that NELF is required for efficient muscle regeneration and stem cell pool replenishment. In mechanistic studies using PRO-seq, single-cell trajectory analyses and myofiber cultures revealed that NELF works at a specific stage of regeneration whereby it modulates p53 signaling to permit massive expansion of muscle progenitors. Strikingly, transplantation experiments indicated that these progenitors are also necessary for stem cell pool repopulation, implying that they are able to return to quiescence. Thus, we identified a critical role for NELF in the expansion of muscle progenitors in response to injury and revealed that progenitors returning to quiescence are major contributors to the stem cell pool repopulation.

overall_design: RNA Pol II position in wild type cultured primary myoblasts


title: Bioplatforms Australia: Antibiotic Resistant Sepsis Pathogens Framework Initiative

sample_organism:
Escherichia coli
Klebsiella pneumoniae
Staphylococcus aureus
Streptococcus pneumoniae
Streptococcus pyogenes
Klebsiella variicola


title: Super Enhancer Regulation of Cytokine-Induced Chemokine Production in Alcoholic Hepatitis [ChIP-Seq 3]

status: Public on Mar 06 2021

city: Rochester

first: Aditya

last: Bhagwate

state: MN

address: 200 1st Street SW

institute: Mayo Clinic

summary: Super enhancer in liver propagates inflammatory signaling by super enhancer-mediatedinducing chemokine expression and is the therapeutic potential of BET inhibition in Alcoholic hepatitis(AH) treatment.

overall_design: For human liver sinusoid endothelial cell (LSEC) ChIP-Seq analyses, control and TNF treated LSECs are collected to perfrom ChIPseq with anti H3k27ac and NFKB antibodies respectively.

first: Vijay

middle: H

last: Shah

first: Sheng

last: Cao

first: Mengfei

last: Liu


title: Floral transition trajectories dissected by single meristem transcriptomes at high temporal resolution.

status: Public on Feb 18 2021

city: Rehovot

first: Zohar

last: Meir

state: Shfela

address: Herzl 234

department: Mathematics & CS

country: Israel

institute: Weizmann Institute of Science

summary: We developed a method we denote as single meristem transcriptome profiling (SMT) and utilize it in this work to analyze hundreds of single tomato shoot-apical-meristems of several genotypes, which were collected during or when approaching floral transition. This provide us with dense temporal sampling of the wild-type process which we used in order to generate a pseudo-time reference, anchored by morphology-based scores. This allows for examination of molecular changes in the genetically-perturbed processes by temporal alignment.

overall_design: Prior to RNA extraction from each homogenized meristem, we recorded the number of leaves it produced, and assigned one of five morphological scores to it (describing subtle nuances in meristem doming). UMI-based cDNA libraries were generated from 12-24 technical replicates of each meristem. UMIs from different wells were then summed together to generate one transcriptional profile for each meristem (see quality-control panels for SMT estimates in Meir, Aviezer et al., 2021).

first: Yuval

last: Eshed

first: Amos

last: Tanay


title: An atlas of neural crest lineages along the posterior developing zebrafish at single-cell resolution

status: Public on Feb 16 2021

city: Houston

first: Rosa

last: Uribe

state: Texas

address: 6100 Main St.

department: BioSciences

institute: Rice University

summary: Neural crest cells (NCCs) are vertebrate stem cells that give rise to various cell types throughout the developing body in early life. Here, we utilized single-cell transcriptomic analyses to delineate NCC-derivatives along the posterior developing vertebrate, zebrafish, during the late embryonic to early larval stage, a period when NCCs are actively differentiating into distinct cellular lineages. We identified several major NCC/NCC-derived cell-types including mesenchyme, neural crest, neural, neuronal, glial, and pigment, from which we resolved over three dozen cellular subtypes. We dissected gene expression signatures of pigment progenitors delineating into chromatophore lineages, mesenchyme subtypes, and enteric NCCs transforming into enteric neurons. Global analysis of NCC derivatives revealed they were demarcated by combinatorial hox gene codes, with distinct profiles within neuronal cells. From these analyses, we present a comprehensive cell-type atlas that can be utilized as a valuable resource for further mechanistic and evolutionary investigations of NCC differentiation.

overall_design: To characterize the neural crest cell lineages present in the posterior zebrafish during the embryonic to larval transition (48-72 hours post fertilization) we utilized single-cell RNA sequencing (scRNA-Seq) on the 10x Genomics Chromium platform to build a dataset from GFP+ cells collected from sox10:GFP embryos.

first: Aubrey

last: Howard

first: Phillip

last: Baker

first: Rodrigo

last: Ibarra-Garcia-Padilla

first: Joshua

last: Moore

first: Lucia

last: Rivas

first: Eileen

last: Singleton

first: Jessa

middle: L

last: Westheimer

first: Julia

last: Corteguera

first: James

last: Tallman


title: Negative Elongation Factor (NELF) regulates muscle progenitor expansion for efficient myofiber repair and stem cell pool repopulation

first: Jeffrey

last: Dilworth


title: Super Enhancer Regulation of Cytokine-Induced Chemokine Production in Alcoholic Hepatitis [RNA-Seq]

status: Public on Oct 19 2020

first: Aditya

last: Bhagwate

overall_design: For human liver RNA-Seq and ChIP-Seq analyses, human liver explants from 6 patients with AH were procured at the time of liver transplant surgery. 4 control patients with no history of chronic liver diseases undergoing liver resection for other causes were obtained to serve as controls.

first: Vijay

last: Shah


title: Super Enhancer Regulation of Cytokine-Induced Chemokine Production in Alcoholic Hepatitis [ChIP-Seq]

summary: We performed histone modification ChIP-Seq in human liver explants and showed upregulation of multiple CXCL chemokines in AH. ChIP-Seq, chromosome conformation capture assays, and in silico analysis of published data identified a super enhancer for multiple CXCL genes. Targeting this super enhancer by dCas9-KRAB-mediated epigenome editing and Bromodomain and Extraterminal (BET) inhibitors decreased the expression of multiple CXCL genes.

overall_design: In the present study, we utilized ChIP-Seq targeting key histone marks in liver explants of AH patients and normal controls to characterize the transcriptomic and epigenomic changes in AH vs. normal.

first: Sheng

last: Cao

first: Mengfei

last: Liu


title: Super Enhancer Regulation of Cytokine-Induced Chemokine Production in Alcoholic Hepatitis


title: Negative Elongation Factor (NELF) regulates muscle progenitor expansion for efficient myofiber repair and stem cell pool repopulation [single-cell RNA]

overall_design: RNA-seq performed on myogenic precursors which were isolated from regenerating skeletal muscle (mouse) at 5 days post-injury for wild type and NELF-B knockout populations.

first: Daniel

last: Robinson

first: F


title: Negative Elongation Factor (NELF) regulates muscle progenitor expansion for efficient myofiber repair and stem cell pool repopulation [RNAseq_48hrs]

overall_design: RNA-seq was performed on myogenic progenitor cells which were FACS isolated from regenerating skeletal muscle 48-hours after skeletal muscle damage was induced with Cartiotoxin. Three replicates were performed for Wildtype (WT) populations, and three replicates performed for NELF-BscKO (KO) populations.

first: Morten

last: Ritso

first: Geoffrey

last: Nelson


title: Negative Elongation Factor (NELF) regulates muscle progenitor expansion for efficient myofiber repair and stem cell pool repopulation [RNA-seq]

summary: Negative Elongation Factor (NELF) is a critical transcriptional regulator that works through stabilizing paused RNA transcripts to permit rapid gene expression changes in response to environmental cues. Whilst NELF is essential for embryonic development, its role in adult stem cells remains unclear. Here, through a muscle stem cell-specific deletion, we show that NELF is required for efficient muscle regeneration and replenishing the stem cell pool. Mechanistic studies using PRO-seq, single cell trajectory analyses and myofiber cultures revealed that NELF works at a specific stage of muscle regeneration whereby it mediates massive expansion of muscle progenitors. Strikingly, transplantation experiments indicate that these progenitors are also necessary for stem cell pool repopulation implying they are able to return to quiescence. Thus, we identified a critical role for NELF in expansion of muscle progenitors in response to injury and revealed that progenitors returning to quiescence are major contributors to stem cell pool repopulation.


title: RNA-seq time course of MSC during osteogenesis

status: Public on Aug 21 2020

city: Oxford

first: chao

last: jiang

address: Botnar Research Centre

department: NDORMS

institute: University of Oxford

overall_design: Examination of gene expression changes during osteogenesis

first: Chao

last: Jiang

first: Martin

last: Philpott

first: Udo

last: Oppermann


title: Negative Elongation Factor (NELF) regulates muscle progenitor expansion for efficient myofiber repair and stem cell pool repopulation [H3K4me3_Cut&Tag]


title: Single cell sequencing of dissected mouse mandibular prominence at embryonic day e11.5 and e13.5

status: Public on Oct 01 2020

city: Cincinnati

first: Samantha

last: Brugmann

state: OH

address: Department of Developmental Biology, DK 1 BLDG R, 240 Albert Sabin Way

institute: Cincinnati Children's Hospital Medical Center

overall_design: Mouse mandibular prominences were dissected at embryonic day 11.5 and 13.5. Tissue were dissociated into single cell suspension and used for single cell RNA library preparation and sequencing using 10X Genomics platform.

first: Kelsey

last: Elliott


title: Single-cell analysis RNA sequencing of prenatal and neonatal gonads/ovaries at E11.5, E12.5, E14.5, E16.5, E18.5, P1 and P5

status: Public on Aug 01 2020

city: Baltimore

first: Allan

last: Spradling

address: 3520 San Martin Drive

institute: Howard Hughes Medical Institute Research Laboratories, Department of Embryology, Carnegie Institution for Science

summary: We sequenced more than 52,500 single cells from E11.5 to P5 gonads to analyze primordial follicles and wave 1 medullar follicles during mouse fetal and perinatal oogenesis. Germ cells clustered into six meiotic substages as well as dying/nurse cells. We also define genes expressed by epithelial progenitors, and clarify the similar but distinct genetic programs of bipotential-derived and epithelial-derived pre-granulosa cell progenitors. Their differentially expressed genes are candidates to control the distinctive developmental programs of wave 1 and wave 2 follicles. These observations provide a strong basis for further studies of the development, physiology, and evolutionary conservation of mammalian ovarian follicle formation.

overall_design: We performed single cell RNA-seq on developing prenatal gonads/ovaries atE11.5 (sex determination), E12.5 (cycle mitotically to form germline cysts), E14.5 (transition to meiosis), E16.5 (progress to pachytene),E18.5 and P1 (organelle transfer, cyst breakdown, oocyte differentiation and germ cell turnover), and P5 (primordial follicle formation).  The selected time points span key events during perinatal ovarian development. After a meticulous dissection and trypsin incubation, ovaries were dissociated into single-cell suspensions. 52,542 dissociated cells were subsequently captured, loaded onto oil droplets, and used for cDNA library construction, deep sequencing, and cluster analysis.  Expression information on an average of 2,700 different genes was recovered from each cell.

first: Wanbao

last: Niu


title: Molecular signatures underlying neurofibrillary tangle susceptibility in Alzheimer’s disease

status: Public on Aug 05 2020

city: Stanford

first: Inma

last: Cobos

address: 300 Pasteur Drive, Lane Building, L235

institute: STANFORD UNIVERSITY MEDICAL SCHOOL

summary: Tau aggregation in neurofibrillary tangles (NFTs) is closely associated with neurodegeneration and cognitive decline in Alzheimer’s disease (AD). However, the molecular signatures that distinguish between aggregation-prone and aggregation-resistant cell states are unknown. We developed methods for the high-throughput isolation and transcriptome profiling of single somas with NFTs fro¬m human AD brain, quantified the susceptibility of 20 neocortical subtypes for NFT formation and death, and identified both shared and cell-type-specific signatures. NFT-bearing neurons shared a marked upregulation of synaptic transmission-related genes, including a core set of 63 genes enriched for synaptic vesicle cycling. Oxidative phosphorylation and mitochondrial dysfunction were highly cell-type dependent. Apoptosis was only modestly enriched, and the susceptibilities of NFT-bearing and NFT-free neurons for death were highly similar. Our analysis suggests that NFTs represent cell-type-specific responses to stress and synaptic dysfunction. We provide a resource for biomarker discovery and the investigation of tau-dependent and tau-independent mechanisms of neurodegeneration.

overall_design: Fresh frozen brain tissue from the prefrontal cortex (BA9) of eight Braak stage VI AD and eight age-matched healthy control donors was micro-dissected and dissociated without detergents or enzymatic digestion. Immunostaining and FACS using an antibody to detect pathological tau aggregates (AT8) and the pan-neuronal marker MAP2 was used to isolate somas with NFTs (n = 24,660) and neighboring NFT-free neurons (n = 38,465) from AD donors and control NFT-free somas (n = 63,110). RNA capture and library preparation was performed using the 10× Genomics Chromium Single Cell 3’ v2 or v3 assay. The generated paired-end libraries were sequenced on Illumina Novaseq 6000. Paired-end sequence reads were processed using the 10× Genomics software package Cell Ranger and the R-based Seurat package. Raw data is available in SRA with Study accession SRP189891 and Bioproject accession PRJNA528824.

first: Marcos

last: Otero-Garcia

first: Yueqiang

last: Xue

first: Tamara

last: Shakouri

first: Yongning

last: Deng

first: Samuel

last: Morabito

first: Riki

last: Kawaguchi

first: Vivek

last: Swarup


title: Prognostic significance of interferon-γ and its signaling pathway in early breast cancer depends on the molecular subtypes

status: Public on Sep 22 2020

city: Mainz

first: Marcus

last: Schmidt

address: Langenbeckstr. 1

department: Universitäres Centrum für Tumorerkrankungen

institute: Universitätsmedizin Mainz

summary: Interferons are crucial for adaptive immunity and play an important role in the immune landscape of breast cancer. Using microarray-based gene expression analysis, we examined the subtype specific prognostic significance of interferon-γ (IFN-γ) as a single gene as well as an IFN-γ signature covering the signaling pathway in 461 breast cancer patients. Prognostic significance of IFN-γ as well as the IFN-γ signature for metastasis-free survival (MFS) were examined using Kaplan Meier as well as univariate and multivariate Cox regression analyses in the whole cohort and in different molecular subtypes. Kaplan Meier curves and univariate Cox regression analyses showed that the prognostic significance of IFN-γ as a single gene was limited to basal-like breast cancer (P=0.033). In contrast, the IFN-γ associated gene signature was a significant prognostic factor in the whole cohort (HR 1.554; 95%CI 1.1099-2.199; P=0.013) as well as in the luminal B (P=0.007) and HER2-positive (P=0.033) molecular subtype with borderline significance in basal-like breast cancer(P=0.050). In multivariate analysis, the IFN-γ signature retained its independent prognostic significance (HR 2.287; 95% CI: 1.410-3.633;P<0.001) in the entire cohort. These results underline the subtype-dependent prognostic influence of the immune system in early breast cancer.

overall_design:
461 patients with early breast cancer, who received surgery between 1986 to 2000 at the Department of Gynecology and Obstetrics of the University Medical Center Mainz, entered the study. We included all consecutive patients with an adequate amount of fresh-frozen tumor tissue available for successful Affymetrix microarray analysis.

***CEL files not available for 109 patients

first: M

last: Gehrmann