status: Public on Apr 17 2020

city: London

first: Leonie

last: Taams

state: london

address: CIBCI, 1.26, New Hunts House

institute: King's College London

summary: Psoriatic arthritis is a seronegative polyarticular form of inflammatory arthritis . Genetic analysis implicates a role for both IL-17/23 axis and CD8+ T cells in disease susceptibility. Using RNA-seq we identified differential gene expression between synovial IL-17A+(IFNy+/-) CD8+ T cells compared to IL-17A-IFNy+ CD8+ T cells and IL-17A+CD4+ T cells from the synovial fluid of psoriatic arthritis patients. We find that IL-17A+CD8+ T cells have a transcriptional overlap with IL-17A+CD4+ T cells. Overall we show these IL-17A+ CD8+ T cells have a polyfunctional, pro-inflammatory capacity and are potentially derived from common precursors, shared with IL-17A-CD8+ T cells.

overall_design: RNA-seq analysis of IL-17A+/IFNy+ CD8+ and IL-17A+CD4+ T cells from Psoriatic Arthritis Synovial Fluid from 3 patients

first: Kathryn

last: Steel

first: Ushani

last: Srenathan

first: Michael

last: Ridley

first: Lucy

last: Durham

first: Bruce

middle: W

last: Kirkham

middle: S


title: Pioneer factor GAF cooperates with PBAP and NURF to regulate transcription

status: Public on May 10 2020

city: Ithaca

first: Julius

last: Judd

state: NY

address: 417 Biotechnology Bldg; 215 Tower Road

department: Molecular Biology and Genetics

country: USA

institute: Cornell University

type: Expression profiling by high throughput sequencing

type: Genome binding/occupancy profiling by high throughput sequencing

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

overall_design: Refer to individual Series


title: Characterization of cochlear development at the single cell level

status: Public on Apr 09 2020

city: Bethesda

first: Robert

last: Morell

state: MD

address: 35A Convent Drive, Room 1F-103

institute: National Institute on Deafness and Other Communication Disorders

summary: The organ of Corti, located in the floor of the scala media of the cochlea, acts as the primary sensory transducer of sound in mammals.  This remarkable structure comprises a highly diverse cellular mosaic that includes two unique types of mechanosensory hair cells and an undefined number of associated supporting cell types.  All of these cells are believed to arise from a developmental equivalence group referred to as the prosensory domain that is similarly thought to arise from a proneurosensory population that develops in the anterior-ventral region of the otocyst.  The results of both classical embryologic manipulations and modern molecular genetic experiments suggest that otocyst precursor cells proceed through several rounds of lineage restriction that progressively specify subsets of cells as prosensory cells and ultimately as either hair cells or supporting cells.  However, the relatively small sizes of the otocyst and inner ear have hindered efforts to determine the full diversity of cell types within the mature cochlea and to identify the transitional cell types that exist during development.  The recent development of droplet-based methods for isolation and subsequent transcriptional profiling of individual cells provides a potential method to address both of these challenges.  Therefore, we dissected, dissociated and then captured over 27,000 epithelial cells from the developing cochlear duct at specific time points between E14 and P7.

overall_design: We characterized the transcriptomic profiles of cochlear epithelium celltypes of E14, E16, P1, P7 wild type (WT) mice at a single cell resolution using 10x Chromium  and Illumina sequencing platforms. Data contain over 27,000 single cells.

middle: C

last: Kelly

first: Likhitha

last: Kolla

first: Matthew

last: Kelley

middle: J


title: CRISPR screen in regulatory T cells reveals ubiquitination modulators of Foxp3 stability

status: Public on Apr 29 2020

city: San Diego

first: Diana

middle: C.

last: Hargreaves

state: CA

address: 10010 North Torrey Pines Road

institute: The Salk Institute for Biological Studies

summary: Regulatory T cells (Tregs) are required to control immune responses and maintain homeostasis, but are a significant barrier to anti-tumor immunity1. Conversely, Treg instability, characterized by loss of the master transcription factor Foxp3 and acquisition of pro-inflammatory properties2, can promote autoimmunity and/or facilitate more effective tumor immunity3,4. A comprehensive understanding of the pathways that regulate Foxp3 could lead to more effective Treg therapies for autoimmune disease and cancer. Despite improved functional genetic tools that now allow for systematic interrogation, dissection of the gene regulatory programs that modulate Foxp3 expression has not yet been reported. In this study, we developed a CRISPR-based pooled screening platform for phenotypes in primary mouse Tregs and applied this technology to perform a targeted loss-of-function screen of 490 nuclear factors to identify gene regulatory programs that promote or disrupt Foxp3 expression. We discovered several novel modulators including , Ataxin 7 like 3 (Atxn7l3) and members of the deubiquitination module of the SAGA chromatin modifying complex, Usp22 and Atxn7l3, were discovered to be positive regulators that stabilized Foxp3 expression; whereas the screen suggested Rnf20, an E3 ubiquitin ligase, is a negative regulator of Foxp3. Treg-specific ablation of Usp22 in mice reduced Foxp3 protein and created defects in their suppressive function that led to spontaneous autoimmunity, but protected against tumor growth in multiple cancer models. Foxp3 destabilization in Usp22-deficient Tregs could be rescued by ablation of Rnf20, revealing a reciprocal ubiquitin switch in Tregs. These results reveal novel modulators of Foxp3 and demonstrate a screening method that can be broadly applied to discover new targets for Treg immunotherapies for cancer and autoimmune disease.

overall_design: ChIP-seq experiments were performed for H2BK120Ub histone modification in regulatory T cells (Tregs) with or without genetic deletion of Usp22 and Rnf20. These data support the finding that USP22 regulates Foxp3 expression by modulating levels of H2BK120Ub at the Foxp3 locus. ChIP-seq experiments were also done to profile binding of USP22 and RNF20 in untreated Tregs.

first: Jovylyn

last: Gatchalian

first: Jessica

middle: T

last: Cortez

first: Elena

last: Montauti

first: Alexander

last: Marson

first: Deyu

last: Fang


title: A maternally inherited polymorphism in mitochondrial genome alters immune cell metabolism and protects mice from skin inflammation

status: Public on Feb 13 2020

city: Lübeck

first: Hauke

last: Busch

state: Schleswig-Holstein

address: Ratzeburger Allee 160

department: Lübeck Institute of Experimental Dermatology

country: Germany

institute: University of Lübeck

summary: Several mitochondrial genetic variants have been associated with different chronic inflammatory diseases. However, experimental proof for the pathogenic relevance of these associations is still missing. We have reported that polymorphisms in the mitochondrial gene MT-ATP8, which encodes a subunit of the mitochondrial ATP synthase, are associated with the autoimmune skin disease bullous pemphigoid. Using a mouse model for this disease, we show here that a SNP in mt-Atp8 determine the severity of autoantibody-induced skin inflammation by modulating T effector cell function and shifting the levels of short chain fatty acids. With respect to the latter, increased levels of propionate are associated with milder disease, and systemic administration of propionate ameliorates disease. By employing the Aldara™-induced psoriasiform dermatitis model, we further demonstrate that the immunomodulatory effects of mt-Atp8 variants are also relevant for autoinflammation. Collectively, our results highlight discrete mitochondrial genetic variants as significant general modulators of skin inflammation and possibly of other organs.

overall_design: Microarray analysis of total RNA prepared from liver samples obtained from four B6 Wildtype and four B6-mtFVB mice. The conplastic mouse strain, C57BL/6J-mtFVB/NJ (B6-mtFVB), was previously generated  (Yu et al., 2009) and was continuously backcrossed for over 25 generations to have WT nuclear geome and a mitochondrial C57BL/6J mt-Atp8 variant (m.7778G>T). WT mice were purchased from Jackson laboratory (Bar Harbor, ME, USA).

first: Saleh

last: Ibrahim

first: Misa

last: Hirose

first: Paul

last: Schilf


title: Transcriptional profiling of intestinal changes following KRasG12D mutation in an APC deficient mutation

status: Public on Dec 31 2019

city: GLASGOW

first: Karen

last: Pickering

state: Scotland

address: Garscube Estate, Switchback Road, Bearsden

country: United Kingdom

institute: CRUK Beatson institute

summary: Activation of KRas in the intestinal epithelium alongside APC loss under the control of VilCreER

overall_design: Expression data from whole intestine comparing VilCreER APCfl/fl to VilCreER APCfl/fl KRasG12D

first: David

last: Vincent


title: RAC-GEF function as a critical factor in intestinal tumourigenesis

summary: Here we investigate the transcription changes in the murine intestine 4 days following loss of APC under the control of Vil-CreErT2 driver.  We compare the RNAseq data from epithelial organoids generated from control (APC loss) intestines to organoids generated from lacking VAV2, VAV3 and TIAM1.  We show that loss of these GEFs supress the APC WNT driven intestinal phenotype in a RAC-dependent manner.

overall_design: Expression data from organoids generated from intestines from VilCreEr APCfl/fl vs VilCreER APCfl/fl Vav2-/-, Vav3-/-, Tiam1-/- mice.


title: Embryonic Atrazine Exposure Causes Behavioral, Transcriptomic, Epigenetic, and Pathological Alterations in Adult Zebrafish Brain [female]

city: West Lafayette

first: Jennifer

last: Freeman

state: IN

address: 550 Stadium Mall Drive

department: School of Health Sciences

institute: Purdue University

summary: According to the developmental origins of health and disease (DOHaD) hypothesis, exposure to environmental stressors during early development can cause genetic, epigenetic, or functional changes in tissues that increase disease risk later in life. Atrazine (ATZ) is a commonly used pesticide that frequently contaminates rural and urban water sources at levels above the 3 ppb maximum contaminant level set by the US Environmental Protection Agency. Exposure to ATZ is linked to endocrine disruption, cancer, changes in genome methylation, and alterations in neurochemistry and behavior. This study tests the hypothesis that embryonic exposure to ATZ results in sex-specific changes in behavior, the adult brain transcriptome, and adult body and brain pathology, according to the DOHaD hypothesis. Zebrafish (Danio rerio) embryos were exposed to 0, 0.3, 3, or 30 ppb (ppb; µg/L) ATZ during the period from fertilization through 72 hours post fertilization (hpf), and then were rinsed and raised to maturity with no further exposure. At 9 months post fertilization (mpf), a novel tank test, a light-dark box, and an open field test evaluated adult behavior. Transcriptomic analysis investigated ATZ related differences in gene expression and the brain was evaluated histopathologically for morphometric alterations in the area of the dorsal telencephalon, posterior tuberculum, and raphe populations. At 14 mpf, the body length, weight, and brain weight was measured to evaluate effects of ATZ on mature body and brain size. The 9 mpf adult behavioral tests found non-monotonic, sex-specific behavior changes, with male zebrafish having decreased activity and female zebrafish having increased signs of anxiety. Transcriptomic analysis identified sex-specific alterations, with females having altered expression of genes in pathways related to cancer and organismal injury and males having altered gene expression in organismal development and reproductive system development and function pathways. Morphometric analysis identified a decreased number of cells in male raphe populations and adult zebrafish also had non-monotonic, sex-specific alterations in body length, body weight, and brain weight. This results suggests that developmental exposure to ATZ does cause sex-specific alterations in adult neural function.

overall_design: We treated zebrafish embryos from approximately 1 hour post fertilization through 72 hours post fertilization (embryogenesis) with 0, 0.3, 3, or 30 ppb atrazine. Following the 72 hour exposure period, larvae were rinsed and reared to 9 months post fertilization. After zebrafish were euthanized, the brains were removed and processed for transcriptomic analysis.

first: Katharine

middle: A

last: Horzmann

first: Li

middle: F

last: Lin

first: Boghos

last: Taslakjian

first: Chongli

last: Yuan

middle: L


title: Relative roles of Stp1 and Stp2 in amino acid and peptide utilization in Candida albicans

status: Public on Feb 20 2020

city: Houston

first: Michael

last: Lorenz

state: TX

address: 6431 Fannin

institute: UTHealth Houston

summary: Candida albicans is a member of the normal commensal flora with the ability to cause disease in susceptible individuals. Nutrient acquisition is of central importance for C. albicans to colonize and thrive in the host. We have previously assessed the role of amino acid utilization for growth and manipulation of pH, triggering the filamentation program and promoting immune evasion. While the role of amino acids has been largely studied, protein utilization has remained less well understood. We investigated the utilization of peptides as a source of carbon and to support the neutralization phenomena. We found that both transcription factors Stp1 and Stp2 are required for proper peptide utilization in a manner dependent of amino acid sensing signaling involving the SPS system. However, we found that Stp2 is the major contributor for this process. Epistasis experiments shown that Stp1 partially restores the ability to utilize peptides in the absence of amino acid signaling, whilst Stp2 is sufficient to fully restore this phenotype. Transcriptomic analysis revealed that the response to amino acids and peptides is very similar, but peptides represent a more difficult carbon source to utilize. It is known that the Stp1/Stp2 duet has divergent roles in C. albicans, however the specific set of genes controlled by each TF remained unclear. We showed that the Stp1 regulon is limited to two oligopeptide transporters (OPT1, OPT9), and iron-acquisition oxidoreductase (CFL2), a nucleoside transporter (NUP) and a leucine aminopeptidase (APE2), whereas Stp2 is responsible for the regulation of amino acid uptake and catabolic genes, in a manner dependent of amino acid sensing. Surprisingly, Stp2 affects expression of genes involved in the filamentation response (e.g. UME6, SFL2) that have been associated with host colonization. In a GI tract competition experiment, mutants lacking the amino acid sensor Ssy1 or the TF Stp2 exhibited decreased colonization, while an stp1Δ/Δ mutant showed increase colonization. Taken together, these results highlight the importance of peptide and amino acid utilization for colonization of the host, a prerequisite for disseminated disease.

overall_design: Examination of wild-type and mutant C. albicans transcriptomes under different carbon source conditions.

first: Pedro

last: Miramón

first: Andrew

last: Pountain

first: Ambro

last: van Hoof


title: Transcriptional profiling of murine intestine during APC-driven tumourigenesis


title: Transcriptional profiling of intestinal changes following APC loss

summary: Vil-CreERT2 was used to drive loss of APC (Adenomatous polyposis coli) in the murine intestinal epithelium.  4 days post induction, mice were sampled and 1cm of tissue from the proximal intestine was collected into RNA later.  This was compared to control (wild-type) intestine.  This analysis allows investigation of transcriptional changes following APC loss (and therefore activation of the WNT signalling pathway).

overall_design: RNAseq Expression data from whole intestine comparing WT intestine vs VilCreER APCfl/fl

first: Owen

last: Sansom

first: Rob

last: Fordham


title: Chromatin accessibility established by Pou5f3, Sox19b and Nanog primes genes for activity during zebrafish genome activation.

status: Public on Jan 08 2020

city: Bergen

first: Gunnar

last: Schulze

state: Hordaland

address: Thormøhlensgt. 55

department: Institute for informatics

country: Norway

institute: University of Bergen

summary: In many organisms, early embryonic development is driven by maternally provided transcription factors until the controlled onset of transcription during zygotic genome activation (ZGA). The regulation of chromatin accessibility and its relationship to gene activity during this transition remains poorly understood. Here, we generated chromatin accessibility maps for the early stages of zebrafish development spanning genome activation and the onset of lineage specification. We find that during this period, chromatin accessibility increases at regulatory elements. This is independent of RNA pol II-mediated transcription, with the exception of the miR-430 locus. Instead, accessibility often precedes the transcription of associated genes. Loss of the maternal transcription factors pou5f3, sox19b, and nanog, which are known to be required for zebrafish ZGA, results in decreased accessibility at regulatory elements. Finally, we show that accessibility of regulatory regions, especially when established by Pou5f3, Sox19b and Nanog, is predictive for future transcription. Together, our results suggest that maternally provided transcription factors prime genes for activity during zygotic genome activation.

overall_design: Chromatin accessibility profiles (ATAC-seq) for zebrafish whole embryos were generated for 7 WT developmental stages (256-cell, high, oblong, sphere, dome, shield, 80%-epiboly),  maternal-zygotic transcription factor mutants (pou5f3(-/-), sox19b(-/-), nanog(-/-) ) at oblong stage and alpha-amanitin treated embryos at oblong stage. Additionally, a nucleosome-free genomic DNA sample was generated as control. Each stage/condition except for the  control was replicated with duplicates or triplicates  and sequenced on an Illumina HiSeq 2500  instrument or NextSeq550 instrument.

first: Máté

last: Pálfy

first: Eivind

last: Valen

first: Nadine

last: Vastenhouw


title: The model metabolic disruptor  DEHP (bis(2-ethylhexyl) phthalate disregulates the gut transcriptome a key player in microbiome-gut axis

city: Gainesville

first: Christopher

last: Martyniuk

state: FL

address: 8891 SW 79th Avenue

institute: University of Florida

summary: Phthalate esters, such as DEHP (bis(2-ethylhexyl) phthalate, are a ubiquitous class of chemicals used as plasticizers in plastic products such as toys and hospital supplies. They are not covalently bound to the polymer matrix and can leach out of products.  The goal of this study is to determine whether DEHP adversely affect the zebrafish (Danio rerio) microbiome-gut axis, specifically gut transcriptome.  We exposed the fish to 3 ppm DEHP via food for 8 weeks to stimulate chronic exposure. To identify genomic responses of DEHP in gut, we used microarrays followed by differential gene expression analysis. The data were then mapped to changes in cell processes and signaling pathways using Pathway Studio.

overall_design: Zebra fish were exposed to one dose of DEHP (3ppm) : control males (n=5), control females (n=6), DEHP males (n=5), DEHP females (n=7)

first: Ondrej

last: Adamovsky


title: BCL6 represents a therapeutic target in E2A-PBX1 and MLL-rearranged acute lymphoblastic leukemia

city: San Francisco

first: Huimin

last: Geng

address: 513 Parnassus Ave., MSB HSW 1201

department: Department of Laboratory Medicine

institute: UCSF

summary: We used ChIPseq to identify target genes of BCL6 that are involved in leukemogenesis of E2A-PBX1 and MLL-AF4 pre-B ALL.

overall_design: ChIP-seq using BCL6 antibodies in RCH-ACV and ICN12 (E2A-PBX1 acute lymphomablastic leukemia), RS4;11, SEM and ICN13 cells (MLL-AF4 rearranged acute lymphomablastic leukemia), and LAX7R cells (relapsed acute lymphomablastic leukemia with KRAS-G12V mutation).

first: Christian

last: Hurtz

first: Markus

last: Muschen

first: Erica

last: Ballabio

first: Thomas

last: Milne


title: Diffuse glioma cells with perineural satellitosis invade by mediating metabolic reprogramming

status: Public on Feb 02 2020

city: Gifu

first: Hiroyuki

last: Tomita

address: 1-1 Yanagido

country: Japan

institute: Gifu University

summary: We developed diffuse glioma cells with H3F3A_K27M mutation.K27M diffuse glioma cells have high migration ability and maintain close contact with neurons with immature neuron-like properties.K27M cells produce neurotrophic factors and lactic acid and affect neurite growth and differentiation/suppression of surrounding neurons. K27M diffuse glioma cells show an invasion type and gene expression patterns similar to those of human glioma.

overall_design: We prepared immortalized murine glial cells (OS3; established and  obtained from  C3H male mouse brain) with H3.3-K27M mutation and control glial cells with the empty vector. We harvested three dishes in each cohort (n=3)  and extracted RNA from each dishes. Finally, we perfomred RNA microarray analysis.

first: Masafumi

last: Miyai


title: Shifts in pigeon limb identity reveal conserved genetic networks

status: Public on Jan 31 2020

city: Athens

first: Douglas

last: Menke

state: GA

address: 500 DW Brooks Drive

institute: University of Georgia

summary: The goal of this study is to identify genetic network changes that accompany shifts in limb identity.

overall_design: mRNA profiles in forelimbs and hindlimbs of Anolis sagrei embryos at stage 7.

first: Sungdae

last: Park

first: Carlos

middle: R

last: Infante

first: Elena

last: Boer

first: Michael

middle: D

last: Shapiro

middle: B


title: Population Structure, and Selection Signatures underlying High-Altitude Adaptation Inferred from Genome-Wide Copy Number Variations in Chinese Indigenous Cattle

status: Public on Feb 21 2020

city: Ji'nan

first: Yaran

last: Zhang

address: North industrial road

country: China

institute: Shandong Acdemy of Agricultural Sciences

summary: Copy number variations (CNVs) have been demonstrated as crucial substrates for evolution, adaptation and breed formation. Chinese indigenous cattle breeds exhibit a broad geographical distribution and diverse environmental adaptability. Here, we analyzed the population structure and adaptation to high altitude of Chinese indigenous cattle based on genome-wide CNVs derived from the high-density BovineHD SNP array. We successfully detected the genome-wide CNVs of 318 individuals from 24 Chinese indigenous cattle breeds and 37 yaks as outgroups. A total of 5,818 autosomal CNV regions (683 bp - 4,477,860 bp in size), covering ~14.34% of the bovine genome (UMD3.1), were identified, showing abundant CNV resources. Neighbor-joining clustering, principal component analysis (PCA), and population admixture analysis based on these CNVs support that most Chinese cattle breeds are hybrids of Bos taurus taurus (hereinafter to be referred as Bos taurus) and Bos taurus indicus (Bos indicus). The distribution patterns of the CNVs could to some extent be related to the geographical backgrounds of the habitat of the breeds, and admixture among cattle breeds from different districts. We analyzed the selective signatures of CNVs positively involved in high-altitude adaptation using pairwise Fst analysis within breeds with a strong Bos taurus background (taurine-type breeds) and within Bos taurus×Bos indicus hybrids, respectively. CNV-overlapping genes with strong selection signatures (at top 0.5% of Fst value), including LETM1 (Fst = 0.490), TXNRD2 (Fst=0.440) and STUB1 (Fst=0.420) within taurine-type breeds, and NOXA1 (Fst = 0.233), RUVBL1 (Fst=0.222) and SLC4A3 (Fst=0.154) within hybrids, were potentially involved in the adaptation to hypoxia. Thus, we provide a new profile of population structure from the CNV aspects of Chinese indigenous cattle and new insights into high-altitude adaptation in cattle.

sample_organism:
Bos taurus
Bos indicus
Bos grunniens

overall_design: We initially genotyped 375 individuals representing 25 Chinese indigenous cattle breeds, as well as 39 individuals representing two yak breeds as outgroups. After quality control filtering for chip data, a total of 355 individuals including 318 Chinese indigenous cattle and 37 yaks (outgroups in our study) were retained and used for further analyses. We detected their genome-wide CNVs, and analyzed their population structure based on these CNVs. We used the pairwise Fst method to explore the selection signatures of CNVs positively involved in high-altitude adaptation, by comparing cattle breeds native to high-altitude plateau with those native to low-altitude land within taurine-type breeds and within Bos taurus×Bos indicus hybrids, respectively.

first: Yan

last: Hu

first: Xiuge

last: Wang

first: Qiang

last: Jiang

first: Han

last: Zhao

first: Jinpeng

first: Zhihua

last: Ju

first: Liguo

last: Yang

first: Yaping

last: Gao

first: Xiaochao

last: Wei

first: Jiachen

last: Bai

first: Yang

last: Zhou

first: Jinming

last: Huang


title: Transcriptome and physiological effects of toxaphene on the liver-gonad reproductive axis in male and female largemouth bass (Micropterus salmoides) [Liver]

status: Public on Dec 20 2019

first: Christopher

last: Martyniuk

summary: Toxaphene (TOX) is an organochlorine pesticide (OCPs) that remains abundant in the environment due to its heavy use in agriculture, its persistence, and its atmospheric transport. In Florida, the north shore of Lake Apopka was heavily used for agriculture decades ago, and TOX remains present in the soil. Wild largemouth bass inhabit the lake, and are potentially exposed to a variety of OCPs. While other OCPs (dieldrin, methoxychlor, p,p’DDE) have been studied for their endocrine disrupting effects in largemouth bass, there are little data available for TOX. Here we performed a 2-month feeding study of male and female largemouth bass with TOX-laced food to mimic the levels found in fish at Lake Apopka. Subsamples of the gonad and liver were collected and preserved in 10% buffered formalin for histopathology and reproductive staging. Plasma levels of vitellogenin (Vtg) testosterone (T) and 17β-estradiol (E2) were quantified and snippets of testis and ovaries were placed into culture to determine ex vivo production of hormones. Lastly, transcriptomics was conducted in both the male testis and liver, as most studies investigating OCPs have analyzed female ovary/liver and data are scarce for OCPs and male bass. Female GSI did not change with TOX but was trending towards a decrease while male GSI did not change with exposure. Female vitellogenin decreased with toxaphene by ~40% but male vitellogenin was not induced. Female and male E2 and T were not different following dietary exposure compared to control bass and this corresponded to ex vivo culture experiments, which revealed no change in E2 and T production from the gonads. Taken together, TOX did not alter the production of E2 and T directly in the gonad tissue. In the testis, transcriptomics revealed that androgen receptor/beta-2-microglobulin signaling was up-regulated while insulin-related pathways were suppressed with TOX. In the liver, the transcriptome analysis revealed an overwhelming suppression in immune-related signaling cascades (e.g. lectin-like receptor and ITSM-Containing Receptor signaling, CD16/CD14 Proinflammatory Monocyte Activation, and CD38/CD3 -> JUN/FOS/NF-kB Signaling in T-cell Proliferation). Ninety percent of the pathways were reduced between 10 to 40% in median network expression. Reduced immune pathways are consistent with other studies investigating OCPs in fish.  In the current study, TOX, at the concentrations tested in the diet, did not act as a weak estrogen as many other OCPs do, but rather appeared to be acting as an antiestrogen (or androgen) based upon reduced female Vtg and activation of androgen-receptor mediated pathways in the testis. These data contribute to a comprehensive transcriptomic-physiological framework for TOX and suggests that endocrine disruption may not be the result of direct effects on steroidogenesis in the gonad, but may rather occur at higher levels of the reproductive axis.

overall_design: Seven or Eight biological replicates performed for microarrays. The liver was n=3 control and n=4 toxaphene-fed animals. Testis was n=4 control and n=4 toxaphene-fed animals

first: Alvine

last: Mehinto

first: Cristina

last: Colli-Dula

first: Kevin

last: Kroll

first: Nicholas

last: Doperalski

first: David

last: S. Barber

first: Nancy

last: Denslow


title: Transcriptome and physiological effects of toxaphene on the liver-gonad reproductive axis in male and female largemouth bass (Micropterus salmoides) [Testis]

last: Barber


title: Microarray data generated from formalin-fixed, paraffin-embedded (FFPE) uninvolved small bowel (SB) ileal tissue.

status: Public on Dec 23 2019

city: Los Angeles

first: Alka

last: Potdar

address: 110 George Burns Rd

department: Medicine/GI

institute: Cedars-Sinai Medical Center

overall_design: Transcriptomic data was generated on uninvolved SB tissue from formalin-fixed paraffin-embedded (FFPE) small bowel resection margins of subjects requiring surgery at Cedars-Sinai Medical Center for Crohn’s disease. The transcriptomic data was generated in two batches (n=100, n=57) and was analyzed as a merged, batch effect corrected dataset (SB157).

first: Kelli

last: VanDussen

first: Janine

last: Bilsborough

first: Dermot

middle: P

last: McGovern


title: Transcriptome and physiological effects of toxaphene on the liver-gonad reproductive axis in male and female largemouth bass (Micropterus salmoides)

overall_design: Refer to individual Series


title: Transcriptome map of the human brain at the single-cell resolution

status: Public on Jan 30 2020

city: Lund

first: Ilia

last: Kurochkin

state: Skane

address: BMC A12, Sölvegatan 17

country: Sweden

institute: Lund University

summary: The human brain is about three times larger than the brain of our closest relatives, chimpanzees and bonobos. However, increased size alone fails to explain cognitive abilities unique to humans. Functional changes acquired in the human lineage are likely mediated by divergent gene expression and cell composition in brain regions. Here we generated a map of the human brain transcriptome by assessing the gene expression levels in 33 distinct regions representing all major brain structures from four adult cognitively healthy human individuals, three chimpanzees, three bonobos, and three rhesus macaques. We further conducted single-nuclei RNA-sequencing (SN-seq) experiment in three of the 33 brain regions in four species: two regions showing excess of the human-specific differences, cingulate anterior cortex and cerebellar gray matter, as well as one region showing no such excess, caudate nucleus. We determined cell type specificity of human-specific differences observed in the bulk tissue analysis, and identified species-specific expression differences directly using SN-seq data. This data resource forms a comprehensive baseline for studies of normal and abnormal human brain function and evolution.

sample_organism:
Macaca mulatta
Pan paniscus
Pan troglodytes
Homo sapiens

overall_design: Single cell mRNA-seq profiling of 3 brain regions: Cingulate Anterior (BA24), Caudate and Cerebellar Gray Matter

first: Ekaterina

last: Khrameeva

first: Philipp

last: Khaitovich


title: Active Notch Signaling is Required for Arm Regeneration ina Brittle Star

city: Kannapolis

first: Robert

last: Reid

state: NC

address: 150 Research Campus Drive, Suite 3333

department: Bioinformatics and Genomics

institute: UNC Charlotte

summary: Cell signaling pathways play key roles to coordinate cellular events in development. Notch signaling pathway is highly conserved across all multicellular animals and is known to co- ordinate a multitude of diverse cellular events, including proliferation, differentiation, fate specification, and cell death. Specific functions of the pathway are however highly context- dependent and are not well characterized in post-traumatic regeneration. Here, we use a small-molecule inhibitor of the pathway (DAPT) to demonstrate that Notch signaling is required for proper arm regeneration in the brittle star Ophioderma brevispina, a highly re- generative member of the phylum Echinodermata. We also employ a transcriptome-wide gene expression analysis (RNA-seq) to characterize the downstream genes controlled by the Notch pathway in the brittle star regeneration.

overall_design: 3 samples versus 3 samples (DAPT treated versusDMSO Control )

first: Vladimir

last: Mashanov

first: Daniel

last: Janies


title: Exploring transcriptomic landscapes in red cell populations, in their extracellular vesicles and on single cell level

city: Helsinki

first: pirkko

middle: maria

last: mattila

address: Tukholmankatu 8

department: FIMM TC

country: Finland

institute: University of Helsinki

summary: Circulating human red blood cells (RBCs) consist of mature erythrocytes, and immature reticulocytes. As being anucleated cells, RBCs lack typical, abundant transcriptomes but are known to contain low amounts of diverse long transcripts and microRNAs. The exact role and importance of these RNAs is, however, lacking. To study this further, we have explored the RNA content of RBCs as well as extracellular vesicles of RBCs using next-generation sequencing (NGS). Furthermore, to understand the dynamics of the RBC transcriptome, we performed single cell RNA sequencing on RBCs both from fresh blood and blood unit. Analysis of the single cell transcriptomes revealed that while the majority of the cells don’t have detectable RNA, the remaining, approximately 10% of the cells fall into three sub-populations based on their RNA content. Overall decrease in the RNA quantity over the populations is observed. Qualitative changes include the differences in the hemoglobin (Hb) content of the cells, and the changes in the expression of ribosomal and mitochondrial genes. A previously unknown transcript of a long non-coding RNA, MALAT1 (Metastasis Associated Lung Adenocarcinoma Transcript 1) is the most enriched marker gene for one subpopulation of RBCs, suggesting a role for MALAT1 in reticulocyte maturation. Enriched pathways in RBC transcriptome, such as autophagy, reflect the processes required for reticulocyte maturation to erythrocytes. RBC transcriptome is transferred to extracellular vesicles (EVs), suggesting the vesiculation as the mechanism to remove the cellular contents at the final stages of erythrocyte maturation.

overall_design: RNAseq on 4 red blood cell samples and their extracellular vesicles.

first: Pirkko

last: Mattila

first: Jenni

last: Lahtela

first: Antti

last: Larjo

first: Laura

last: Mäenpää

first: Erja

last: Kerkelä


title: Identification of osteoclast coupling factors in humans reveals links between bone remodeling and energy metabolism.

status: Public on Dec 07 2019

city: Rochester

first: Sundeep

last: Khosla

state: MN

address: 200 1st St SW

department: Endocrinology Research

institute: Mayo Clinic

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


title: Identification of osteoclast coupling factors in humans reveals links between bone remodeling and energy metabolism I

summary:
Purpose:  Identification of osteoclast derived coupling factors using Denosumab as a biological probe
Method: harvested RNA from centrifuged bone biopsies (heterogeneous population containing bone lining cells, osteoblasts, osteoclasts and osteocytes, without in vitro culture
Results:  Identification of genes differentially regulated in denosumab treated participants that correlate with bone remodeling indices
Conclusions:  Using this approach we identified denosumab regulated genes that correlate with bone remodeling in the untreated participants and may represent novel osteoclast derived coupling factors. Of interest, we identified DPP4 to be suppressed in denosumab treated participants, providing a novel link between bone remodeling and energy metabolism.

overall_design:
Examination of gene expression of centrifuged bone biopsies isolated three months after treatment with placebo or denosumab in post-menopausal women or untreated in young women.

Please note that GSM6246351-GSM6246365 sample records have been added on June 15, 2022.

first: Megan

last: Weivoda


title: RNA-Sequenzing of Streptomyces coelicolor A3(2) (M1152) in timeseries

status: Public on Oct 09 2019

city: Tübingen

first: Kay

last: Nieselt

state: DE

address: Sand 14

department: Department for Computer Science

institute: Institute for Bioinformatics and Medical Informatics

summary: SYSTERACT: Systematic Rebuilding of Actinomycetes for Natural Product Formation    For several decades antibiotics have saved millions of lives, but their overuse makes them less effective due to increase in bacterial resistance. Because of this major clinical and public health problem, there is an urgent need for new effective antimicrobials.   The ERASysAPP project SYSTERACT aims to further develop, the model actinobacterium Streptomyces coelicolor into improved microbial cell factories to heterologously produce diverse bioactive compounds in amounts needed for structural and functional evaluation. Unprecedented systems biology understanding of S. coelicolor is being combined with morphology engineering and improved (de-)regulation and precursor supply to accelerate bioactive compound discovery efforts. By that means, we aim to generate a stepwise improved 'Superhost' for the production of antibiotics in which metabolic bottlenecks and regulatory restriction are greatly mitigated. The optimized strains will be tested concerning their applicability for an improved production of commercially relevant antibiotics and the expression of novel bioactive gene clusters identified in new actinomycete strains and environmental metagenomes.     So far two strains, M145 and M1152, have been cultivated for time-resolved 'omics sampling, and a larger number of additional strains are on the list for similar experiments. High quality RNAseq-based transcriptome data have been generated and processed.  M145 is the wildtype strain in S. coelicolor (as used in STREAM, see also GSE18489), 3 biol. replicas and M1152 lacks four major biosynthetic gene clusters,   undecylprodigine (RED), calcium-dependent antibiotic (CDA), coelimycin (CPK) and actinorhodin (ACT).    Contributors:  A. Wentzel, W. Wohlleben, G. van Wezel, D van Dissel, O. Wolkenhauer, E. Kerkhoven, N. Spidsoe, K. Nieselt and the SYSTERACT consortium

overall_design:
RNA-seq expression analysis of timeseries based around phosphate depletion
[contributor] SYSTERACT consortium

first: A

last: Wentzel

first: W

last: Wohlleben

first: G

last: van Wezel

first: D

last: van Dissel

first: O

last: Wolkenhauer

first: E

last: Kerkhoven

first: N

last: Spidsoe

first: K


title: RNA-Sequencing of Streptomyces coelicolor A3(2) (M145) in timeseries


title: Local Modulation of Lymph Node Stroma by Sensory Neurons

status: Public on Oct 31 2019

city: Cambridge

first: Alex

last: Shalek

state: MA

address: 77 Massachusetts Ave

department: Chemistry

institute: Massachusetts Institute of Technology

summary: Immune responses within barrier tissues are regulated, in part, by nociceptors, specialized peripheral sensory neurons that detect noxious stimuli. Previous work has shown that nociceptor ablation not only alters local responses at peripheral sites of immune challenge, but also within draining lymph nodes (LNs). The mechanism and significance of nociceptor-dependent modulation of LN homeostasis are unknown. Indeed, although sympathetic innervation of LNs is well documented, it has been unclear whether the LN parenchyma itself is innervated by sensory neurons. Here, using a combination of high-resolution imaging, retrograde viral tracing, optogenetics, and single-cell transcriptomics (scRNA-seq), we describe a sensory neuro-immune circuit that is preferentially located in the outermost cortex of skin-draining LNs. Transcriptomic profiling revealed that sensory neurons that innervate LNs are composed of at least four discrete subsets with a predominance of peptidergic nociceptors, an innervation pattern that is distinct from that in the surrounding skin. To identify potential LN-resident communication partners for LN-innervating sensory neurons, we employed scRNA-seq to generate an atlas of all murine LN cells and, based on receptor-ligand expression patterns, nominated candidate target populations among stromal and immune cells. We experimentally validated these inferred connections by comparing scRNA-seq signatures before and after selective optogenetic stimulation of LN-innervating axons. Acute neuronal activation triggered rapid transcriptional changes preferentially in endothelium and other nodal stroma cells, as well as in several innate leukocyte populations. Thus, LNs are monitored by a unique population of sensory neurons that possess profound immunomodulatory potential.

overall_design: We implemented a Cre-lox based viral labeling strategy that enabled reliable identification and isolation of the cell bodies of LN-innervating neurons in DRGs. Briefly, we injected a Cre-expressing recombinant adeno-associated virus, AAV2/1-Cre, a serotype with broad tropism towards DRG neurons, into the right iLN of Rosa26LSL-tdTomato/LSL-tdTomato mice carrying a Cre-dependent tdTomato reporter. Upon entry into sensory fibers, this non-replicating virus travels retrogradely to the cell body in DRGs where virally encoded Cre recombinase deletes a genomic floxed 'stop' sequence resulting in expression of tdTomato. We harvested ipsilateral T13 and L1 DRGs from injected animals to manually isolate individual tdTomato+ neurons as previously described (Hempel et al., 2007). Each isolated cell was then subjected to scRNA-Seq using the Smart-Seq2 protocol to yield a final dataset of 52 LN-innervating sensory neurons from 8 mice. As a control and reference population, we also generated scRNA-Seq libraries from 31 skin-innervating neurons from 4 Rosa26LSL-tdTomato/LSL-tdTomato mice that were retrogradely labeled by intradermal injection of AAV2/1-Cre.

first: Siyi

last: Huang

first: Carly

middle: G

last: Ziegler

first: John

last: Austin

first: Najat

last: Mannoun

first: Jose

last: Ordovas-Montanes

first: Marko

last: Vukovic

middle: K

first: Ulrich

middle: H

last: von Andrian


title: Topologically Associated Domains Delineate Susceptibility to Somatic Hypermutation

status: Public on Dec 04 2019

city: Safed

first: Yaakov

last: Maman

address: Henrietta Szold 8

department: Azrieli Faculty of Medicine

country: Israel

institute: Bar-Ilan University

summary: Somatic hypermutation (SHM) introduces point mutations into immunoglobulin (Ig) genes of activated B cells to support the process of antibody affinity maturation but also causes "off-target" mutations in other parts of the genome.  We have used sensitive lentiviral SHM reporter vectors and a mutationally active human B cell line to identify dozens of regions of the genome that are intrinsically susceptible to SHM ("hot" regions) and many hundreds of regions that are resistant to SHM ("cold" regions).  Hot and cold regions are frequently contained within topologically associated domains (TADs).  Comparison of hot and cold TADs reveals that while overall levels of transcription are equal, hot TADs are enriched for NIPBL (a component of the cohesin loader), super enhancers, markers of paused/stalled RNA polymerase 2, and multiple transcription factors implicated in B cell development and targeting of SHM.  We demonstrate that at least some hot TADs contain enhancer elements that possess SHM targeting activity and that insertion of a strong Ig SHM-targeting element into a cold TAD renders it hot. Our findings lead to a model for SHM susceptibility involving the cooperative action of cis-acting SHM targeting elements and the dynamic and architectural properties of TADs.

overall_design: 27 samples of ChIP-seq profiles in Ramos cell line including the Input and H3 control samples. 30 samples of HTISA libraries showing GFP7 integration site profiles in Ramos cell line. 2 samples of ATAC-seq profile in Ramos cell line. 4 samples of Hi-C profile in Ramos cell line.

first: Filip

last: Senigl

first: Ravi

last: Dinesh

first: Jukka

last: Alinikula

first: Rashu

last: Seth

first: Lubomira

last: Pecnova

first: Arina

last: Omer

first: Suhas

last: Rao

first: David

last: Weisz

first: Jean-Marie

last: Buerstedde

first: Erez

last: Aiden

first: Rafael

last: Casellas

first: Jiri

last: Hejnar

last: Schatz


title: An RNA-Seq atlas of gene expression in rose flower under treatment of various phytohormones and plant growth regulators

status: Public on Nov 20 2019

city: beijing

first: liu

last: xintong

institute: China Agricuture university

summary: Using RNA-seq, we recently investigated the transcriptomic dynamics of rose flower under treatment of various plant hormones, including ethylene, 2,4-D, NAA, cytok, gibberellins, abscisic acid, brassinosteroids, salicylic acid, jasmonates, as well as ethylene inhibitor 1-MCP and AgNO. We obtained approximately 240GB data and dissected the transcriptional network with the aim of exploring the transcriptional variation of rose responses towards those plant hormones. Our data will be useful to all those working with the analysis of rose gene expression.

overall_design: 39 samples include 11 plant hormones or its inhibitors, H2O/ET-CK are controls for liquid/ gas hormones.

first: Xintong

last: Liu

first: Jie

last: Wu


title: Local Modulation of Lymph Node Stroma by Sensory Neurons II

status: Public on Nov 01 2019

first: Alex

last: Shalek

overall_design: Left and Right Inguinal LNs from 7 mice were digested using a modified protocol for gentle cellularization (Fletcher et al. Front Immunol 2011). A portion of cells were retained for Seq-Well scRNA-seq representing the "whole" or un-depleted fraction, the remaining were depleted of CD3e and CD19 expressing cells using the Miltenyi microbead kit, and run on Seq-Well arrays in parallel. To specifically activate LN-innervating neurons in vivo, 4 of the 7 mice were Nav1.8Cre/+ x Rosa26ChR2-eYFP/+ (ChR2+) in which Nav1.8 lineage neurons expressed ChR2. The Left iLN-innervating sensory neurons were selectively activated with blue light (473 nm) directed through an optical fiber (200 µm tip diameter) towards a region of the subiliac artery adjacent to the hilus, the predominant site where sensory nerve bundles enter the iLN. A control cohort of 3 Nav1.8Cre/+ x Rosa26eYFP/+ (ChR2-) animals, which expressed eYFP instead of ChR2 in Nav1.8 lineage neurons, were subjected to identical photostimulation, dissociation, cellular enrichment, and Seq-Well analysis.

first: Siyi

last: Huang

first: Carly

last: Ziegler

first: John

last: Austin

first: Najat

last: Mannoun

first: Jose

last: Ordovas-Montanes

first: Marko

last: Vukovic

first: Ulrich

last: von Andrian


title: The impact of pro-inflammatory cytokines on the β-cell regulatory landscape provides insights into the genetics of type 1 diabetes

status: Public on Sep 20 2019

city: Badalona

first: Mireia

last: Ramos-Rodríguez

address: Carretera de Can Ruti, camí de les escoles s/n

department: Division of Endocrinology

country: Spain

institute: Germans Trias i Pujol University Hospital and Research Institute

summary: Early stages of type 1 diabetes (T1D) are characterized by local autoimmune inflammation and progressive loss of insulin-producing pancreatic β cells. We show here that exposure to pro-inflammatory cytokines unmasks a marked plasticity of the β-cell regulatory landscape. We expand the repertoire of human islet regulatory elements by mapping stimulus-responsive enhancers linked to changes in the β-cell transcriptome, proteome and 3D chromatin structure. Our data indicates that the β cell response to cytokines is mediated by the induction of novel regulatory regions as well as the activation of primed regulatory elements pre-bound by islet-specific transcription factors. We found that T1D-associated loci are enriched of the newly mapped cis-regulatory regions and identify T1D-associated variants disrupting cytokine-responsive enhancer activity in human β cells. Our study illustrates how β cells respond to a pro-inflammatory environment and implicate a role for stimulus-response islet enhancers in T1D.

overall_design: Five independent preparations of EndoC-βH1 cells examined under 2 conditions (control and pro-inflammatory cytokine exposure)

first: Jean-Valery

last: Turatsinze

first: Lorenzo

last: Pasquali

first: Decio

last: Eizirik


title: An in-vivo brain-bacteria interface in the Xenopus brainless model reveals developmental brain as a key element of innate immunity

status: Public on Sep 30 2019

first: Christopher

last: Martyniuk

summary: Over the past few years, interest in the field of neuroimmunology has expanded dramatically.  While recent data and hypotheses suggest immunity as the ‘seventh sense’ to inform brain about microorganisms, the role of the brain to protect against infection is unknown. We demonstrate here that the brain signaling is an essential part of the innate immunity. In absence of a brain, survival rates of embryos injected with pathogenic E.coli decreased significantly. This effect was not due to actions of brain on immune cells or on early development of the immune system, but it is dynamically induced by the bacterial infection. Sub-network analysis revealed potential genes and signaling pathways mediating the protective effects of the brain. Taken together, these data identify a new protective role for the developmental brain and reveal revealed a number of regulated transcripts, including those  pathways that represent novel targets for immune therapies

overall_design: There were two biological replicates per treatment (brain intact, not infected; brain intact infected; brainless, not infected; brainless, infected).

first: Celia

last: Herrera-Rincon

first: Jean

last: Pare

first: Christina

last: Harrison

first: Alina

last: Fischer

first: Mike

last: Levin


title: transcriptome analysis of dgk5 mutant in response to flagellin-Transcriptome analysis of dgk5 mutant

status: Public on Sep 25 2019

city: Orsay

first: Stéphanie

last: Pateyron

address: Rue de Noetzlin _ Batiment 630

country: France

institute: IPS2_Institute of Plant Sciences Paris-Saclay

summary: au16-02_dgk5 - transcriptome analysis of dgk5 mutant in response to flagellin - Is the dgk5.1 mutant impaired in its response to flagellin? - We compare seedlings grown in liquid medium treated or not with flagellin. Seedlings are either Col-0 or the mutant dgk5.

overall_design: 6 dye-swap - normal vs transgenic comparison,treated vs untreated comparison

first: Eric

last: Ruelland

first: Sandrine

last: Balzergue

first: Marie-Laure

last: Martin-Magniette


title: Transcriptional response of Staphylococcus aureus XN108 vs its ccpA gene knock out

status: Public on Sep 01 2019

city: chongqing

first: huagang

last: peng

address: Gaotanyan

department: Department of Microbiology

institute: Army Medical University

summary: Explore the genome-scale influence of ccpA gene knock out on Staphylococcus aureus XN108

overall_design: Samples were taken from the XN108 with ccpA gene knock out. Three independent experiments were performed

first: Huagang

last: Peng


title: Landscape of intercellular crosstalk in fatty liver disease revealed by single-cell secretome analysis

status: Public on Aug 08 2019

city: Ann Arbor

first: Jiandie

last: Lin

state: MI

address: 210 Washtenaw Ave

department: Cell & Developmental Biology, Life Science Institute

institute: University of Michigan

summary: Cell-cell communications via ligand-receptor signaling are a fundamental feature of complex organs. In addition to hepatocytes, the mammalian liver harbors several distinct cell types, including endothelial cells, hepatic stellate cells (HSC), cholangiocytes, the resident macrophage Kupffer cells, and other immune cells, collectively known as non-parenchymal cells (NPC) 1-5. Paracrine signaling among NPC is important for tissue homeostasis and has been implicated in the pathogenesis of nonalcoholic steatohepatitis (NASH), an emerging epidemic linked to metabolic syndrome 6-8. Despite this, the global landscape of intercellular signaling in the liver has not been comprehensively elucidated. Here we perform single-cell RNA sequencing and secretome analysis on liver NPC isolated from healthy and diet-induced NASH mice. Our analysis revealed highly specific patterns of the cellular sources of secreted ligands and membrane receptors and a network of paracrine and autocrine signaling at the single-cell level. Comparative analysis of secretome gene expression uncovered a global disruption of the liver endothelial signaling network during NASH pathogenesis. The HSC secretome encompasses extracellular matrix proteins, signaling ligands (stellakines) and three distinct functional classes of membrane receptors. Liver macrophage undergoes a marked expansion in NASH with the emergence of a new population marked by expression of Triggering receptor expressed on myeloid cells 2 (Trem2) and activation of a transcriptional program underlying phagocytosis, lysosomal degradation and antigen presentation. These results provide a high-resolution blueprint of intercellular crosstalk in mammalian liver and illustrate the complexity and richness of cell-cell signaling in liver physiology and disease.

overall_design: Single cell RNA-seq on non-parenchymal cells of healthy vs NASH mouse liver.

first: Xuelian

last: Xiong

first: Henry

last: Kuang

first: Sahar

last: Ansari

first: Tongyu

last: Liu


title: Transcriptome data after TRIM28 knockdown in A375 melanoma cells

status: Public on Jun 21 2019

city: Stockholm

first: Alexander

last: Espinosa

address: Visionsgatan 18

department: Dept of Medicine

institute: Karolinska Institutet

summary:
TRIM28 is a bromodomain protein implicated in the regulation of tumor growth. TRIM28 regulates gene expression by recruiting epigenetic writers including HDACs, SETDB1 and HP1.
To determine the role of TRIM28 in melanoma cells we knocked down TRIM28 using lentiviral shRNA constructs followed by gene expression analysis using HTA 2.0 GeneChip.

overall_design: Eight samples were analyzed. Four control samples (non-targeting control shRNA) and four experimental samples (TRIM28-specific shRNA).

first: William

last: Nyberg


title: The effects of the pesticide fipronil in rat N27 dopaminergic cells

status: Public on Aug 22 2019

city: Gainesville

first: Christopher

last: Martyniuk

address: 8891 SW 79th Avenue

institute: University of Florida

summary: Six samples of N27 cells were treated with 25 uM fipronil, and 6 samples were not treated (control). The treatment proceeded for 24 hours.

first: Chris

last: Souders


title: Transcriptome studies of marine natural products 4a and 4d on non-small cell lung cancer A549 cells

status: Public on Jun 26 2019

city: Shanghai

first: Cheng

last: Luo

state: Shanghai

address: No. 555 Zuchongzhi Road

institute: Shanghai Institute of Materia Medica

summary: Two novel polyketides, ocellatusones A and B (1 and 2), characterized by either an uncommon oxatricyclo[4.2.1.02,4]nonane skeleton (1) or a mesitylene connected dimethylfuran-3(2H)-one nucleus (2), were isolated in racemic forms from the South China Sea sacoglossan Placobranchus ocellatus, together with seven uncommon polypropionates (3, 4a,4d, 5, and 6). Compounds 1 and 2 were further separated by chiral HPLC to their corresponding enantiomers (±)-1 and (±)-2, respectively. The structures, including absolute configurations, of the new compounds, were unambiguously determined by extensive spectroscopic analysis, quantum chemical computation, and/or X-ray diffraction analysis. The new compounds (+)-1, 4a, 4b, 4d exhibited interesting dose dependent cytotoxic effect on human cancer cell lines, including non-small cell lung cancer and acute promyelocytic leukemia, with IC50 values ranging from 6.1 μM to 28.8 μM. A plausible bio-photosynthetic pathway of these isolates was proposed.

overall_design: The RNA-Seq data was collected for A549 cells after the treatment of Compound 4a, Compound 4d, and Erlotinib

first: Heng

last: Xu

first: Hao

last: Zhang

first: Xu-Wen

last: Li


title: Loss of voltage dependent anion channel 1 affects mitochondrial bioenergetics in rat dopamine cells

status: Public on Jul 31 2019

summary: Voltage dependent anion channel 1 (VDAC1) is a multi-functional protein that regulates mitochondrial membrane potential, calcium regulation, and apoptosis. VDAC1 also interacts with a number of signaling pathways important for energy homeostasis and proteins involved in neurodegenerative diseases such as alpha-synuclein. To identify novel signaling pathways dependent upon VDAC1 protein in dopamine cells, we used CRISPR-Cas9 gene editing in rat immortalized dopaminergic N27 cells. Western blot confirmed that VDAC1 protein levels were reduced ~90%. Mitochondrial bioenergetics was assessed to determine if there was functional loss of mitochondrial function without VDAC1. Loss of VDAC1 resulted in lower ATP-linked and maximum respiration, and spare respiratory capacity. Transcriptomics was conducted in these cells to identify the pathways perturbed by loss of VDAC. This study sheds novel insight into the different regulatory roles mediated by VDAC1 in dopamine cells.

overall_design: Five wild type cell cultures and seven wild type VDAC knockout cell cultures were gown to 80% confluence and assessed for mitochondrial bioenergetics and transcriptomics.

last: Vulpe

first: Amin

last: Sobh

first: Ondrej

last: Adamovsky

first: Eliza

last: Balazic

first: Anna

last: Rushin


title: Long-term repopulation of Langerhans cell network following immune injury is inefficient and solely dependent upon influx of monocyte precursors

status: Public on Jun 14 2019

city: London

first: Stephen

last: Henderson

address: Paul O'Gorman Building

department: Cancer Institute

institute: UCL

summary: RNAseq gene expression following the repopulation  of the langerhans cell network in immune deficient irradiated mice after ectopic injection of donor bone marrow cells

overall_design: Allogeneic bone marrow transplantation with donor T cells leads to destruction of epidermal Langerhans cells (LC).  This study aimed to investigate if and how the LC network was replaced under these conditions. We demonstrated that monocytes entered the epidermis and differentiated into monocyte-derived LC that were homologous to the cells they had replaced.

first: Clare

last: Bennett

first: Heather

last: West


title: Heterozygous mutations in SMARCA2 lead to impaired neurogenesis due to global retargeting of SMARCA4

status: Public on Jul 30 2019

city: San Diego

first: Diana

last: Hargreaves

address: 10010 North Torrey Pines Road

institute: The Salk Institute for Biological Studies

summary: Mammalian SWI/SNF complexes are multi-subunit chromatin remodeling complexes associated with an ATPase, either SMARCA4 or SMARCA2. Heterozygous mutations in the SMARCA2 ATPase cause Nicolaides-Baraitser Syndrome (NCBRS), an intellectual disability syndrome associated with delayed speech onset. We engineered human embryonic stem cells (hESCs) to carry NCBRS-associated heterozygous SMARCA2 K755R or R1159Q mutations. While SMARCA2 mutant hESCs were phenotypically normal, differentiation to neural progenitors cells (NPCs) was severely impaired. We find that SMARCA2 mutations cause enhancer reorganization with loss of SOX3-dependent neural enhancers and prominent emergence of astrocyte-specific de novo enhancers. Changes in chromatin accessibility at enhancers were associated with an increase in SMARCA2 binding and retargeting of SMARCA4. We show that AP-1 family member FRA2 is aberrantly overexpressed in SMARCA2 mutant NPCs, where it functions as a pioneer factor at de novo enhancers. Together, our results demonstrate SMARCA2 mutations cause impaired differentiation through enhancer reprogramming via inappropriate targeting of SMARCA4.

overall_design: RNA-seq of human Neural Progenitor Cell(hNPC) derived from WT, K755R/+, R1159Q/+ H9 human embryonic stem cell(hESC).  ChIP-seq of H3K4me, H3K4me3, H3K27me, H3K27ac, SMARCA2, SMARCA4, FRA2, SOX2, SOX3 in WT, K755R/+, R1159Q/+  hNPCs. ChIP-seq of AM in R1159Q/+ hNPCs with lenti-viral expression of SMARCA2-WT-AM or SMARCA2-R1159Q-AM. ChIP-seq of SMARCA4 in WT hNPCs with siCT or siSOX2/SOX3. ChIP-seq of SMARCA2 and SMARCA4 in K755R/+ hNPCs with siCT or siFOSL1/siFOSL2/siJUNB. ATAC-seq of WT, K755R/+, R1159Q/+  hNPCs. ATAC-seq of K755R/+ hNPCs with siCT or siFOSL1/siFOSL2/siJUNB.

first: Fangjian

last: Gao

first: Josephine

last: Ho


title: Expression array of human macrophages on plastic or mesentery tissue in the presence or absence of MMP inhibitors

status: Public on May 01 2019

middle: J.

last: Weiss

address: 210 Washtenaw Avenue

department: Life Sciences Institute

summary: Macrophages dominate inflammatory environments where they modify the extracellular matrix by mobilizing complex repertoires of proteolytic enzymes.  Nevertheless, the dominant proteinases used by macrophage as they confront physiologic tissue barriers remain undefined.  Herein, we have characterized the molecular mechanisms that define human macrophage-extracellular matrix interactions ex vivo.  Resting and immune-polarized macrophages are shown to proteolytically remodel basement membranes while infiltrating the underlying interstitial matrix.  In an unbiased screen to identify key proteases, we find that the macrophage metalloproteinase, MT1-MMP, is the dominant effector of basement membrane degradation and invasion. Unexpectedly, macrophages can alternatively use actomyosin-dependent forces to transmigrate native basement membrane pores that provide cells with proteinase-independent access to the interstitial matrix. These studies not only identify MT1-MMP as a key proteolytic effector of extracellular matrix remodeling by human macrophages, but also define the invasive strategies used by macrophages to traverse physiologic tissue barriers.

overall_design: Human peripheral blood monocytes were isolated from whole blood of volunteers in accordance with institutional review board (IRB) approval and the patient’s informed consent. PBMCs were separated by Lymphocyte Separation Medium (Corning) by density centrifugation, purified by CD14 selection (Miltenyi Biotec) and cultured in 20% autologous serum until differentiating into mature macrophages. Macrophages were stimulated with 1ug/ml LPS on plastic or decellularized rat mesenetery tissue and in the presence or absence of 5 um BB-94 and harvested for RNA extraction and hybridization on Affymetrix microarrays.

first: Julian

last: Bahr


title: RNA-sequencing of epicardial adipose tissue of patients with atrial fibrillation

status: Public on Aug 07 2019

city: Beijing

first: Lei

last: Zhao

state: Beijing

address: Gongti Nanlu No.8

institute: Beijing Chaoyang Hospital

summary: Accumulating studies have suggested that epicardial adipose tissue play an important role in the pathogenesis of atrial fibrillation (AF), but few have characterized the underlying mechanism between their interactions. Recent evidence suggested that bioactive molecules secreted from EAT, including exosomes carrying non-coding RNAs, may modulate atrial remodeling. The aim of the present study was to investigate the expression profile of mRNAs and ncRNAs in EAT with AF.

overall_design: Epicardial adipose samples collected from patients with persistent non-valvular AF (n=6) and sinus rhythm (n=6) were profiled using RNA-sequencing on the Illimina HiSeq 4000.

first: Xinchun

last: Yang


title: Expression array of Mt1-mmp+/+ and Mt1-mmp-/- mouse macrophages in response to LPS or IL-4

summary: Macrophages dominate inflammatory environments where they modify the extracellular matrix by mobilizing complex repertoires of proteolytic enzymes.  Nevertheless, the dominant proteinases used by macrophage as they confront physiologic tissue barriers remain undefined.  Herein, we have characterized the molecular mechanisms that define human macrophage-extracellular matrix interactions ex vivo.  Resting and immune-polarized macrophages are shown to proteolytically remodel basement membranes while infiltrating the underlying interstitial matrix.  In an unbiased screen to identify key proteases, we find that the macrophage metalloproteinase, MT1-MMP, is the dominant effector of basement membrane degradation and invasion.  These studies not only identify MT1-MMP as a key proteolytic effector of extracellular matrix remodeling by human macrophages, but also define the invasive strategies used by macrophages to traverse physiologic tissue barriers.

overall_design: Primary mouse bone marrow derived macrophages from global knockout [Mt1-mmp(-/-)] mice and wild-type [Mt1-mmp(+/+)] littermates on an outbred Swiss Black background were cultured for 24 hours in the presence of growth media alone or supplemented with 1ug/ml LPS or 20ng/ml IL-4 and harvested for RNA extraction and hybridization on Affymetrix microarrays.


title: Genome-wde mapping of BRD9 binding sites and gene expression changes upon BRD9 knockdown

status: Public on May 02 2019

city: Rotterdam

first: Ning Qing

last: Liu

address: Wytemaweg 80

department: Hematology

country: Netherlands

institute: Erasmus University Medical Center Rotterdam

summary: Leukemia is characterized by genetic and epigenetic mutations resulting in selection of cancer cells, which are unable to differentiate. While genetic alterations are difficult to target, the epigenome is intrinsically dynamic and readily offers new therapeutic strategies. Thus, identifying cancer-specific context-dependent targets and unraveling their biological function may open up new therapeutic perspectives. Here, we identify bromodomain-containing protein 9 (BRD9) as a critical target required in acute myeloid leukemia (AML). We show that BRD9 is overexpressed in AML cells including ex vivo primary blasts compared to CD34+ cells. By targeting BRD9 expression in AML, we observed an alteration in proliferation and survival, ultimately resulting in the induction of apoptosis. Intriguingly, genome-wide profiling revealed that BRD9 binds enhancer regions in a cell type-specific manner, regulating cell type-related processes. We unveil a novel BRD9-sustained STAT5 pathway activation via regulation of SOCS3 expression levels. Our findings identify a previously undescribed BRD9-STAT5 axis as critical for leukemia maintenance, suggesting BRD9 as a potential therapeutic target.

overall_design: Mapping BRD9 binding sites in U937 and HeLa cells, and examine expression changes upon shBRD9 in U937 cells

first: Nunzio

last: Del Gaudio

first: Ning

middle: Q

first: Lucia

last: Altucci


title: Tabula Muris

status: Public on Jun 04 2019

city: San Francisco

first: Angela

last: Oliveira Pisco

address: 499 Illinois St

department: Data Science

institute: Chan Zuckerberg Biohub

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

overall_design: Refer to individual Series


title: Expression array of Mt1-mmp+/+ and Mt1-mmp-/- mouse macrophages and human macrophages in the presence or absence of MMP inhibitors

sample_organism:
Homo sapiens
Mus musculus

platform_organism:
Homo sapiens
Mus musculus


title: Intra-Tumor DNA Methylation Heterogeneity in Glioblastoma; Implications for DNA Methylation-based Classification

status: Public on Feb 27 2019

city: Gothenburg

first: Helena

last: Carén

address: Medicinaregatan 1F

institute: University of Gothenburg

summary: Background: A feature of glioblastoma (GBM) is the cellular and molecular heterogeneity, both within and between tumors. This variability results in a risk for sampling bias and potential tumor escape from future targeted therapy. Heterogeneous gene expression within GBM is well documented, but little is known regarding the epigenetic heterogeneity. We therefore aimed to profile the intra-tumor DNA methylation heterogeneity in GBM. Methods: 3-4 biopsies per tumor from spatially separated regions were collected from 12 GBM patients. We performed genome-wide DNA methylation analysis (~850,000 CpG sites) and compared inter- and intra-tumor variation. Results: All samples were classified as GBM IDH wt or IDH mutated by DNA methylation profiling, but the GBM subtype differed within five tumors. Some GBM samples exhibited higher DNA methylation differences within tumors than between, and many CpG sites (mean: 17,000) had different methylation levels within the tumors. Conclusions: We demonstrated that intra-tumor DNA methylation heterogeneity is a feature of GBM. Although all biopsies were classified as GBM IDH wt/mutated by DNA methylation analysis, the assigned subtype differed in samples from the same patient. The observed DNA methylation heterogeneity within tumors is important to consider for methylation-based biomarkers and future improvements in stratification of GBM patients.

overall_design: We investigated the intra-tumor DNA methylation heterogeneity in glioblastoma using Infinium MethylationEPIC for bisulphite-converted DNA from 3-4 samples per tumor from 12 adult glioblastoma patients (38 samples), and from 3 adult meningioma patients (9 samples) as a homogeneous reference giving a total of 47 samples.

last: Wenger

first: Sandra

last: Ferreyra Vega

first: Teresia

last: Kling

first: Thomas

last: Olsson Bontell

first: Asgeir

middle: S

last: Jakola


title: Genome-wide maps of gene expression in alkaline sphingomyelinase knockout mice

status: Public on Jan 01 2019

city: Daqing

first: Jiang

last: Zhu

state: Hei Longjiang

address: Xinyang Road 39, Gaoxin District

institute: Daqing Branch of Harbin Medical University

summary: Intestinal alkaline sphingomyelinase (alk-SMase) generates ceramide and inactivates platelet-activating factor and associated with digestion and inhibition of cancer. There is few study to analyze the correlated function and characterize the genes related to alk-SMase comprehensively. In this work, deep RNA sequencing was performed to investigate the function of alk-SMase. Our RNA-seq data found 239 differentially expressed mRNAs between the wild type (WT) mice and alk-SMase (gene NPP7) knockout (KO) mice, in which 73 were significantly up-regulated and 166 were down-regulated, including protein coding genes, non-coding RNAs. Notably, the results of gene ontology functional enrichment analysis indicated that differentially expressed genes were functionally associated with the immune response, regulation of cell proliferation and development related terms using DAVID. Additionally, an integrated PPI and KEGG network was chose to study the relationship of differentially expressed genes, it was shown that some modules was significantly related to alk-SMase and with accordance of previously results. We chose 6 of these genes randomly were validated the accuracy of RNA-seq technology using quantitative real-time polymerase chain reaction (qPCR) and 2 genes showed difference significantly (P<0.05).

overall_design: Mouse intestinal tissues were harvested from three pairs of wildtype and alk-SMase knockout mice. Total RNA was extracrted with TRizol method according to manufacturer’s instructions. RNA samples were deeply sequenced using Illumina Hiseq2500 platform after further cleaning-up using Qiagen RNeasy mini columns, and 50bp single end reads were genetated.

first: Ping

last: Zhang


title: Gene expression profiling in Silurana (Xenopus) tropicalis exposed to mixtures of naphthenic acids

status: Public on Nov 29 2018

first: Christopher

last: Martyniuk

summary: Naphthenic acids (Nas) are carboxylic acids present in crude oil and classfied as emergent pollutants. The mechanisms underlaying the toxicity of such mixtures are unknown. Changes in gene expression are expected to reflect te teratogenenic effects of the exposure to NAs. The objective of these experiments is to determine the changes in the gene expression profile of Silurana (Xenopus) tropicalis embryos due to the exposition to two NA mixtures.

overall_design: 3 treatment groups: Control, naphthenic acids mixture 1, naphthenic acids mixtue 2 (n = 4 per group). The napthenic mixtures were two batches of Sigma catalog number 70340 (BCBC9959V and BCBK0736V).

first: Juan

middle: M

last: Gutierrez-Villagomez

first: Vance

last: Trudeau

first: Chris

middle: J


title: The inner ear heat shock transcriptional signature identifies otoprotective compounds against aminoglycoside ototoxicity

status: Public on Dec 31 2018

city: Bethesda

first: Robert

last: Morell

state: MD

address: 35A Convent Drive, Room 1F-103

institute: National Institute on Deafness and Other Communication Disorders

summary: RNA-Seq analysis of adult mouse cultured utricles exposed to 43C heat shock for 30 minutes and recovered for 2 hours in order to generate a heat shock signature for cultured mouse inner ear tissue

overall_design: Utricles were dissected from P30-P60 CBA/J mice (male and female) and cultured, each RNASeq replicate contains 5-6 utricles pooled together

first: Matthew

last: Ryals

first: Lisa

last: Cunningham

first: Erich

middle: W

last: Boger


title: Dysbiotic microbiome triggers Th17 cells to mediate oral mucosal immunopathology in mice and humans

summary: Animal model implicates microbiota-triggered oral mucosal Th17 cells as drivers of local immunopathology and therapeutic targets in periodontitis.

overall_design: Total RNA from gingival tissues from mice undergoing experimental periodontitis . Each mouse has a ligated (induction site) side and a control side and mice are treated with an inhibitor of TH17 inflammation  (GSK805 (RORγt Inverse Agonist II)) or vehicle control. We are interested in the differences in gingival inflammation in the presence/absence of the inhibitor. Mice have a strong response to treatment by clinical score.

first: Teresa

last: Greenwell-Wild

first: Daniel

last: Martin

first: Niki

last: Moutsopoulos


title: CSMD1 shows complex somatic alterations in esophageal squamous cell carcinoma based on a pilot integrated analysis [Affy_500K]

status: Public on Oct 31 2018

first: Howard

last: Yang

address: 37 CONVENT DR, Room 5120

department: CCR

institute: NCI

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

summary: Since ESCC is a complex and heterogeneous disease, it is increasingly important that analyses combine the evaluation of alterations in DNA, including somatic copy number alterations (SCNA), which distinguished from germ line copy number variants, allelic imbalance and LOH, and RNA, including those that occur in both mRNA and miRNA on the same specimen. Thus, in order to better understand their potential interactions in the development of cancers, in the present study, we studied alterations at DNA level as well as expression of mRNA and target miRNA in tumors and their matched normal tissues from 56 ESCC cases on a candidate tumor suppressor gene CSMD1 to characterize there alterations in this gene for import insights into the cellular detect that cause the complex disease, ESCC.

overall_design: Affymetrix SNP arrays were performed according to the manufacturer's directions on DNA extracted from esophageal squamous cell carcinoma diagnosed or peripheral blood samples.

first: Chaoyu

last: Wang


title: CSMD1 shows complex somatic alterations in esophageal squamous cell carcinoma based on a pilot integrated analysis [Affy_SNP5]


title: CSMD1 shows complex somatic alterations in esophageal squamous cell carcinoma based on a pilot integrated analysis


title: Transcriptomic Analysis of a Pseudomonas-Resistant versus a Susceptible Arabidopsis Accession

city: Beer-Sheva

first: Isabel

last: Orf

department: Life Sciences

institute: Ben-Gurion University of the Negev

summary: Even though accessions of one species are genetically very closely related to each other, they may show significantly different susceptibility or resistance towards abiotic and biotic stresses. The Arabidopsis thaliana accessions Col-0 and C24 differ significantly in their resistance against the pathogen Pseudomonas syringae pv. tomato (Pst). To identify the molecular mechanisms contributing to this naturally occurring variety in resistance against Pst, we analysed changes in transcripts in Col-0 and C24 upon infection with Pst.

overall_design: 24 Samples, mock treatment samples serve as controls for corresponding Pst infection samples

first: Hezi

last: Tenenboim

first: Nooshin

last: Omranian

first: Jan

last: Lisec

first: Thomas

last: Altmann

first: Patrick

last: Giavalisco

first: Zoran

last: Nikoloski

first: Lothar

last: Willmitzer

first: Yariv

last: Brotman


title: Massively parallel single-cell chromatin landscapes of human immune cell development and intratumoral T cell exhaustion

status: Public on Apr 16 2019

city: Pleasanton

first: Preyas

last: Shah

address: 7068 Koll Center Pkwy #401

institute: 10x Genomics

summary: Understanding complex tissues requires single-cell deconstruction of gene regulation with precision and scale. Here we present a massively parallel droplet-based platform for mapping transposase-accessible chromatin in tens of thousands of single cells per sample (scATAC-seq). We obtain and analyze chromatin profiles of over 200,000 single cells in two primary human systems. In blood, scATAC-seq allows marker-free identification of cell type-specific cis- and trans-regulatory elements, mapping of disease-associated enhancer activity, and reconstruction of trajectories of differentiation from progenitors to diverse and rare immune cell types. In basal cell carcinoma, scATAC-seq reveals regulatory landscapes of malignant, stromal, and immune cell types in the tumor microenvironment. Moreover, scATAC-seq of serial tumor biopsies before and after PD-1 blockade allows identification of chromatin regulators and differentiation trajectories of therapy-responsive intratumoral T cell subsets, revealing a shared regulatory program driving CD8+ T cell exhaustion and CD4+ T follicular helper cell development in association with clinical response. We anticipate that droplet-based single-cell chromatin accessibility will provide a broadly applicable means of identifying regulatory factors and elements that underlie cell type and function.

overall_design: We used scATAC product from 10x Genomics to profile cell lines, human immune cells and solid biopsies from basal cell carcinoma patients before and after immunotherapy treatment.

first: Jeff

last: Granja

first: Grace

last: Zheng


title: DNA methylation profiles of human blood samples from Hispanic subjects with Parkinson's disease

status: Public on Sep 04 2018

city: Los Angeles

first: Steve

last: Horvath

state: CA

address: 695 Charles E. Young Drive South, Box 708822

department: Human Genetics

institute: University of California, Los Angeles

type: Methylation profiling by genome tiling array

summary:
Human DNA methylation Beadchip v1.2 was used to profile n=84 whole blood samples from Hispanics living in the USA.
The main goal of the study was to relate Parkinson's disease status to measures of epigenetic age acceleration based on DNA methylation data. Here we focus on Hispanic subjects. To measure DNA methylation age, we used the epigenetic clock software described in Horvath S (n=2013) DNA methylation age of human tissues and cell types. Genome Biology.2013, 14:R115. DOI: 10.1186/10.1186/gb-2013-14-10-r115 PMID: 24138928.

overall_design: We analyzed whole blood samples from n=84 samples (46 subjects with PD and 38 control samples). The data come from The Parkinson's disease, Environment, and Genes (PEG) case-control study (wave 1) that aims to identify environmental risk factors (e.g. neurotoxic pesticide exposures) for Parkinson's disease.

first: Beate

last: Ritz


title: A non-canonical BRD9-containing BAF chromatin remodeling complex regulates naïve pluripotency in mouse embryonic stem cells

status: Public on Oct 19 2018

first: Diana

middle: C.

last: Hargreaves

summary: The mammalian BRG1-associated factors (BAF) complex is a multi-subunit chromatin remodeling complex that is an important component of the embryonic stem cell (ESC) transcriptional regulatory network. However, the role of individual subunits in BAF complex targeting and function needs to be elucidated. Here, we find that the Bromodomain containing protein 9 (BRD9) and Glioma tumor suppressor candidate region gene 1 (GLTSCR1; also known as BICRA) or its paralog GLTSCR1-like (also known as BICRAL) define a smaller, non-canonical BAF complex (GBAF for GLTSCR1/1L-containing BAF complex) in mouse ESCs that is distinct from the canonical embryonic stem cell BAF (esBAF) and the polybromo-associated BAF (PBAF) complexes. GBAF lacks several esBAF subunits, including BAF47, BAF57 and ARID1A. We demonstrate that GBAF and esBAF complexes are targeted to different features of the genome and are co-bound with different sets of pluripotency transcription factors. Specifically, GBAF complexes co-localize with key regulators of naïve pluripotency, KLF4 and Sp5, on the genome. Consistent with this, we provide evidence that GBAF's specific function is to regulate the transcription of genes involved in the maintenance of naïve pluripotency, including Nanog and Prdm14. Additionally, we show that BRD9 is displaced from chromatin by the selective BRD9 bromodomain inhibitor, I-BRD9, and that this leads to changes in target gene expression. The function of the GBAF complex in ESCs is highly correlated with the function of BRD4, consistent with an association between GBAF complexes and BRD4. We find that GBAF complexes are directly recruited to chromatin by BRD4 in a bromodomain-dependent fashion and we identify a set of I-BRD9- and JQ1-sensitive BRD9 binding sites that determine the functional similarity between these epigenetic regulators. Together, our results demonstrate functionally specific roles for BAF complex assemblies in maintaining the transcriptional network of pluripotency, highlighting the biological importance of complex heterogeneity.

overall_design: ChIP-Seq of BRD9, BRG1, ARID1A and BRD4 in v6.5 mouse embryonic stem cells (mESCs), RNA-Seq of control or Brd9 knocked down populations in v6.5 mESCs, RNA-Seq of DMSO or I-BRD9-treated mESCs at 24 or 48 hour timepoints, RNA-Seq of control or ARID1A knockout populations using Arid1af/f:CreERT2 ESCs.

first: Jovylyn

last: Gatchalian

first: Josephine

last: Ho


title: Defining the developmental program leading to meiosis in maize

status: Public on Oct 10 2018

city: Athens

first: Brad

last: Nelms

address: 120 E Green St

institute: University of Georgia

summary: We isolated pre-meiotic and early meiotic cells from 24 maize anthers, covering a week of development from the day after archesporial (AR) cell specification to the early zygotene stage of meiotic prophase I. Starting material was staged by anther length, and anther stages were densely sampled from throughout this period. High quality reads were obtained from 144 cells.

overall_design: Single-cell RNA-seq of premeiotic and early meiotic cells from maize anthers. Libraries were constructed with a modified version of CelSeq2.

first: Virginia

last: Walbot


title: Identification of cell type specfici markers for type I and type II Hair cells in the mouse utricle using single cell RNAseq

status: Public on Nov 21 2018

first: Robert

last: Morell

summary: Single cell RNAseq analysis of hair cells isolated from the mouse utricle at three postnatal time points

overall_design:
Utricular hair cells were isolated at P12 (49 cells) and P100 (23 cells) and then combined with a previously published single cell data set (samples from GSE71982) containing 35 utricular hair cells isolated at P1 (Burns et al., 2015)

The previously published single cell P1 samples have been re-normalized. These samples are included in this series and all processed data are available in the file ute_normalized_data.txt, available at the foot of this record.

first: Stephen

last: McInturff

first: Joseph

middle: C

last: Burns

first: Matthew

last: Kelley


title: Robust prediction of response to immune checkpoint blockade therapy in metastatic melanoma

status: Public on Aug 20 2018

city: Philadelphia

first: Tian

last: Tian

state: PA

address: 3615 Civic Center Blvd

department: Center of Applied Genomics

institute: Children's Hospital of Philadelphia

summary: Immune checkpoint blockade (ICB) therapy provides remarkable clinical gains, where melanoma is at the forefront of its success. However, only a subset of patients with advanced tumors currently benefit from these therapies, which at times incur considerable side-effects and costs. Constructing such predictors of patient’s response has remained a serious challenge due to the complexity of the immune response and the shortage of large ICB-treated patient cohorts including both omics and response data. Here we build IMPRES, a predictor of ICB-response in melanoma which encompasses 15 pairwise transcriptomics relations between immune checkpoint genes. It is based on two key conjectures: (a) immune mechanisms underlining spontaneous regression in neuroblastoma can predict ICB response in melanoma, and (b) key immune interactions can be captured via specific pairwise relations of immune checkpoint genes’ expression. IMPRES is validated on 9 published datasets1–6 and on a newly generated dataset of 31 tumor samples treated with anti-PD-1 and 10 tumor samples treated with anti-CTLA-4 (some of these are treated with both antibodies), spanning 297 samples in total. It achieves an overall accuracy of AUC=0.83, outperforming existing predictors, capturing almost all true responders while misclassifying less than half of the non-responders.  Future studies are warranted to determine the value of the approach presented here in other cancer types.

overall_design:
RNA was purified from patients' frozen or formalin-fixed tumor specimens and subject to quality control.  RNA samples of good quality were sequenced.

For some patients, samples were taken at multiple time points or different biopsies from the same time point.

first: Zhang

last: Gao


title: Defects in the alternative splicing-dependent regulation of REST cause deafness

status: Public on Jun 28 2018


title: Transcriptional effects of small molecule targeting of ARID1A

status: Public on Jul 27 2018

summary: We used RNA-seq to characterize the effects of ARID1A knockout on gene expression in mouse embryonic stem cells (ESCs).

overall_design: RNA-Seq of control or ARID1A knockout populations using Arid1af/f:CreERT2 ESCs

first: Benjamin

last: Carter


title: DNA methylation profiles of human blood samples from Caucasian subjects with Parkinson's disease

summary:
Human DNA methylation Beadchip v1.2 was used to profile 508 whole blood samples.
The main goal of the study was to relate Parkinson's disease status to measures of epigenetic age acceleration based on DNA methylation data. Here we focus on Caucasian subjects. To measure DNA methylation age, we used the epigenetic clock software described in Horvath S (n=2013) DNA methylation age of human tissues and cell types. Genome Biology.2013, 14:R115. DOI: 10.1186/10.1186/gb-2013-14-10-r115 PMID: 24138928.

overall_design: We analyzed whole blood samples from n=508 samples (289 subjects with PD and 219 control samples). The data come from The Parkinson's disease, Environment, and Genes (PEG) case-control study (wave 1) that aims to identify environmental risk factors (e.g. neurotoxic pesticide exposures) for Parkinson's disease.


title: Defects in the alternative splicing-dependent regulation of REST cause deafness - [mouse utricles].

summary: The DNA-binding protein REST forms complexes with histone deacetylases (HDACs) to repress neuronal genes in non-neuronal cells. In differentiating neurons, REST is downregulated predominantly by transcriptional silencing. Here we report that post-transcriptional inactivation of REST by alternative splicing is required for hearing in humans and mice. We show that in the mechanosensory hair cells of the mouse ear, regulated alternative splicing of a frameshift-causing exon into the Rest mRNA is essential for the derepression of many neuronal genes. Heterozygous deletion of this alternative exon of mouse Rest causes hair cell degeneration and deafness, and the HDAC inhibitor SAHA (Vorinostat) rescues the hearing of these mice. In humans, inhibition of the frameshifting splicing event by a novel REST variant is associated with dominantly inherited deafness. Our data reveal the necessity for alternative splicing-dependent regulation of REST in hair cells, and identify a potential treatment for a group of hereditary deafness cases.

overall_design: RNA-seq was used to generate utricular mRNA profiles of E15.5 wild-type (WT) mice and mutant mice that are heterozygous for the deletion of exon 4 of Rest (Rest[+/deltaExon4]).

first: Yoko

last: Nakano

first: Michael

last: Kelly

first: Atteeq

middle: U

last: Rehman

first: Erich

middle: T

last: Boger

first: Thomas

last: Friedman

first: Botond

last: Bánfi


title: Defects in the alternative splicing-dependent regulation of REST cause deafness - [mouse cultured organ of Corti].

overall_design: RNA-seq analysis of the mRNA profiles of FK228- and solvent-incubated organ of Corti cultures. These organ cultures were derived from wild-type (WT) mice and mutant mice that are heterozygous for the deletion of exon 4 of Rest (Rest[+/deltaExon4]).


title: Maternal methionine supplementation alters the epigenome of the offspring

status: Public on Jul 17 2018

city: Madison

first: Francisco

last: Peñagaricano

state: Wisconsin

address: 1675 Observatory Drive

department: Animal and Dairy Sciences

institute: University of Wisconsin-Madison

type: Methylation profiling by high throughput sequencing

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

overall_design: Refer to individual Series


title: Defects in the alternative splicing-dependent regulation of REST cause deafness - [mouse brain cortex].

overall_design: RNA-seq was used to generate cortical mRNA profiles of E15.5 wild-type (WT) mice and mutant mice that are heterozygous for the deletion of exon 4 of Rest (Rest[+/deltaExon4]).


title: The RNA sequencing of brain after microglial depletion and repopulation

status: Public on Feb 24 2018

first: Bo

last: Peng

address: 138 Yixueyuan Road

department: Institute for Translational Brain Research

institute: Fudan University

overall_design: Brain mRNA profiles of adult wild type C57BL/6J mice, after treatments of PLX5622, control diet (CD), LPS, vehicle control or microglial repopulation (RP). RP = PLX5622 treated for 14 days, followed by CD (control diet) treatment for a variable number of days. e.g., RP 7 stands for this mouse was treated by PLX5622 for 14 days first, then treated by CD for 7 days. For the LPS-challenged group, mice were administered LPS (1 mg/kg B.W., IP) once a day for 4 days and sacrificed 24 h after the final dose.

first: Guangrong

last: Qin


title: The pesticide fipronil affects transcriptional networks related to mitochondrial dysfunction and methylation in zebrafish embryos (Danio rerio)

status: Public on Jan 31 2018

first: Christopher

last: Martyniuk

address: 8891 SW 79th Avenue

institute: University of Florida

summary: The phenylpyrazole fipronil is a widely used insecticide designed to inhibit γ -amino-butyric acid (GABA) receptors, the major inhibitory neurotransmitter in the central nervous system. Fipronil has been detected in some water systems in the ng/L range, and is reported to be neurotoxic. To address the risks associated with fipronil exposure, we measured morphological, physiological, and molecular responses in zebrafish (Danio rerio) embryos following a 48 hour exposure (20 ng/L – 2 mg/L). Survival was not different than controls following treatments below 200 µg fipronil/L but was ~20% higher with concentrations above 200 µg fipronil/L. Once the embryos hatched, they underwent a 7 day depuration phase.  At 9 days post-fertilization (9 dpf), body length and notochord length were not different than controls for any dose. To assess sub-lethal effects, transcriptome profiling was conducted in 9 dpf larvae following 48 hour exposure + 7 dpf depuration to environmentally relevant concentrations of fipronil (200 ng fipronil/L), as well as two higher concentrations of the pesticide (200 µg fipronil/L and 2 mg fipronil/L). Transcriptome profiling revealed that all three concentrations affected pathways related to chromosome condensation and the metabolism of estrogens and androgens as well as genes related to methylation. In addition, 200 ng fipronil/L down-regulated genes related to the circadian clock, histone and DNA methylation, and histone acetylation, while the highest dose increased networks related to immune function (e.g. lectin-induced complement pathway and the alternative complement pathway). The two highest concentrations of fipronil increased the expression of transcriptional networks associated with mitochondrial respiratory chain dysfunction and mitochondrial protein transport. As such, we exposed 24 hpf embryos to fipronil for 24 hours and measured oxygen consumption rate to assess mitochondrial function. There were no differences in basal and maximal respiration in the embryos nor ATP production, and fipronil did not affect mitochondrial bioenergetics. This study suggests that fipronil at environmentally relevant concentrations does not adversely affect the survival or morphology of fish embryos, however sub-lethal endpoints should be examined to more fully characterize the long term effects of fipronil exposure in larval fish.

overall_design: Three doses of fipronil: Ethanol control (n=6), low (0.2 ug/L) (n=5), medium (200 ug/L) (n=6) and high (2000 ug/L) (n=6)

first: Ashley

last: Eadie

first: Andrew

last: Cowie

first: Chris


title: Endometrial cell-type specific RNA-seq

status: Public on Nov 07 2017

city: Tartu

first: Viktorija

last: Kukushkina

address: Riia 23b

country: Estonia

institute: Estonian Genome Center, University of Tartu

summary: Cell-type specific RNA-seq is a powerful approach for unravelling molecular processes of endometrial receptivity, and to detect novel sensitive biomarkers of receptivity.

overall_design: 16 paired endometrial tissue samples from pre-receptive (defined as LH2) and receptive phase endometria (defined as LH8) from Estonia (defined as E) and Spain (defined as S) were collected. CD9-positive epithelial cells (defined as epithelium) and CD13-positive stromal cells (defined as stroma) were isolated with fluorescent activated cell sorting (FACS) and full transcriptome analysis was performed by RNA-seq.

first: Mariann

last: Koel

first: Kaarel

last: Krjutškov

first: Merli

last: Saare

first: Dmitri

last: Lubenets

first: Aparna

last: Reddy

first: Grete-Katariine

last: Kuum

first: Külli

last: Samuel

first: Shintaro

last: Katayama

first: Elisabet

last: Einarsdottir

first: Lalit

last: Kumar

first: Kristina

last: Gemzell Danielsson

first: Fredrik

last: Lanner

first: Pilar

last: Albero

first: David

last: Blesa

first: Carlos

last: Simon

first: Juha

last: Kere

first: Signe

last: Altmäe

first: Andres

last: Salumets


title: ALV-J and REV synergistically increase the accumulation of miRNAs

status: Public on Jan 11 2018

city: Tai'an

first: Defang

last: Zhou

address: Daizong street NO.61

institute: Shandong Agricultural University

type: Non-coding RNA profiling by high throughput sequencing

summary: The aim of this study was to identify the miRNAs in  CEF in response to synergistic infection of ALV-J and REV, as well as attempt to reveal the mechanism underlying pathogenesis and immune suppression symptoms.

overall_design: CEFs infected with Mock, ALV-J, REV or both viruses were analyzed using miRNA whole-genome sequencing at 72 hpi,

first: Ziqiang

last: Cheng


title: ARID1A and ARID1B loss in TOV21G cells

status: Public on Sep 29 2017

first: Diana

last: Hargreaves

address: 10010 North Torrey Pines Road

institute: The Salk Institute for Biological Studies

summary: ARID1A, a subunit of the SWI/SNF chromatin remodeling complex, is frequently mutated in cancer. Deficiency in its homolog ARID1B is synthetically lethal with ARID1A mutation. However, the functional relationship between these homologs has not been explored. Here we use ATAC-seq, genome-wide histone modification mapping, and expression analysis to examine colorectal cancer cells lacking one or both ARID proteins. We find that ARID1A has a dominant role in maintaining chromatin accessibility at enhancers, while the contribution of ARID1B is evident only in the context of ARID1A mutation. Changes in accessibility are predictive of changes in expression and correlate with loss of H3K4me and H3K27ac marks, nucleosome spacing, and transcription factor binding, particularly at growth pathway genes including MET. We find that ARID1B knockdown in ARID1A mutant ovarian cancer cells causes similar loss of enhancer architecture, suggesting that this is a conserved function underlying the synthetic lethality between ARID1A and ARID1B.

overall_design: ATAC-seq, histone modification ChIP-seq, RNA-seq in TOV21G ovarian clear cell carcinoma cells expressing shRNA targeting ARID1B or scrambled control.

first: Timothy

last: Kelso

first: Devin

last: Porter


title: ARID1A and ARID1B loss in HCT116 and TOV21G cells


title: ARID1A and ARID1B loss in HCT116 cells

overall_design: ATAC-seq, histone modification ChIP-seq, RNA-seq in WT and homozygous ARID1A knockout HCT116 colorectal cancer cells expressing shRNA targeting ARID1B or scrambled control.