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Distinct Gene Regulatory Pathways for Human Innate Versus Adaptive Lymphoid Cells

ABSTRACT: This SuperSeries is composed of the SubSeries listed below. Refer to individual Series

ORGANISM(S): Homo sapiens

SUBMITTER: Eugene Oltz

PROVIDER: E-GEOD-78897 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Distinct Gene Regulatory Pathways for Human Innate versus Adaptive Lymphoid Cells.

Koues Olivia I OI Collins Patrick L PL Cella Marina M Robinette Michelle L ML Porter Sofia I SI Pyfrom Sarah C SC Payton Jacqueline E JE Colonna Marco M Oltz Eugene M EM

Cell 20160505 5

Innate lymphoid cells (ILCs) serve as sentinels in mucosal tissues, sensing release of soluble inflammatory mediators, rapidly communicating danger via cytokine secretion, and functioning as guardians of tissue homeostasis. Although ILCs have been extensively studied in model organisms, little is known about these "first responders" in humans, especially their lineage and functional kinships to cytokine-secreting T helper (Th) cell counterparts. Here, we report gene regulatory circuitries for fo ...[more]

PMID: 27156452

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Distinct Gene Regulatory Pathways for Human Innate Versus Adaptive Lymphoid Cells [ChIP-seq & ATAC-seq]

Project description:Innate lymphoid cells (ILCs) serve as sentinels in mucosal tissues, sensing release of soluble inflammatory mediators, rapidly communicating danger via cytokine secretion, and functioning as guardians of tissue homeostasis. Although ILCs have been studied extensively in model organisms, little is known about these âfirst respondersâ in humans, especially their lineage and functional kinships to cytokine-secreting T helper cell (Th) counterparts. Here, we report gene regulatory circuitries for four human ILCâTh counterparts derived from mucosal environments, revealing that each ILC subset diverges as a distinct lineage from Th and circulating natural killer cells, but shares circuitry devoted to functional polarization with their Th counterparts. Super-enhancers demarcate cohorts of cell identity genes in each lineage, uncovering new modes of regulation for signature cytokines, novel molecules that likely impart important functions to ILCs, and potential mechanisms for autoimmune disease SNP associations within ILCâTh subsets. Molecular profiling of innate lymphoid and T helper cells subsets purified from tonsils and NK cells purified from peripheral blood using Assay for Transposase-Accessible Chromatin (ATAC) and chromatin immunoprecipitation (H3K4me3 and H3K27ac).

2016-05-13 | E-GEOD-77299 | biostudies-arrayexpress

Piwi modulates chromatin accessibility by regulating multiple factors including histone H1 to repress transposons

Project description:PIWI-interacting RNAs (piRNAs) mediate transposable element (TE) silencing at the transcriptional or post-transcriptional level in animal gonads. In the Drosophila ovary, Piwiâ??piRNA complexes (Piwiâ??piRISCs) repress TE transcription by modifying the chromatin state, such as H3K9me3 marks. Here, we demonstrate that Piwi physically interacts with linker histone H1. Depletion of Piwi decreases H1 density on target loci, leading to TE derepression. Loss of H1 results in gain of chromatin accessibility at target loci without affecting H3K9me3 and heterochromatin protein 1a (HP1a) density at the same loci. Piwi-mediated TE silencing also requires HP1a by regulating chromatin accessibility through its association with target loci. Thus, Piwiâ??piRISCs require both H1 and HP1a to repress TEs, and the silencing is correlated with the state of chromatin formation rather than H3K9me3 marks. These findings suggest that Piwiâ??piRISCs regulate the interaction of chromatin components with target loci to maintain silencing of the TE state through the modulation of chromatin accessibility. RNA levels, H1 and H3K9me3 occupancy, chromatin accessibility, and Piwi-associated small RNA levels in ovarian somatic cells (OSC) depleted of piRNA pathway components and H1.

2016-06-30 | E-GEOD-81434 | biostudies-arrayexpress

Histone Reader BRWD1 Targets and Restricts Recombination to the Igk Locus

Project description:B lymphopoiesis requires that immunoglobulin genes be accessible to RAG1-RAG2 recombinase. However, the RAG proteins bind widely to open chromatin, which suggests that additional mechanisms must restrict RAG-mediated DNA cleavage. Here we show that developmental downregulation of interleukin 7 (IL-7)-receptor signaling in small pre-B cells induced expression of the bromodomain-family member BRWD1, which was recruited to a specific epigenetic landscape at Igk dictated by pre–BCR-dependent Erk activation. BRWD1 enhanced RAG recruitment, increased gene accessibility and positioned nucleosomes 5? to each J? recombination signal sequence. BRWD1 thus targets recombination to Igk and places recombination within the context of signaling cascades that control B cell development. Our findings represent a paradigm in which,at any particular antigen-receptor locus, specialized mechanisms enforce lineage- and stage-specific recombination. ChIP-seq for 1 transcription factor and 2 histone modifications in flow purified mouse small pre-B cells. ATAC-seq and RNA-seq in WT and Brwd-Mut mouse flow purified small pre-B cells.

2015-08-24 | E-GEOD-63302 | biostudies-arrayexpress

Foxn1 choreographs both early and late events in thymic lympho-stromal cross-talk

Project description:Normal thymic T cell development is enabled by a stromal microenvironment most importantly composed of distinct epithelial cell populations in cortex and medulla. Their differentiation, growth and function require the expression of the transcription factor Foxn1. Direct targets of Foxn1 have, however, remained largely undefined. Utilizing newly created static and inducible genetic model systems, we now provide a genome wide map of Foxn1 target genes and the sequences bound by this master regulator. Foxn1 controls not only essential steps early in intrathymic lymphoid development including T cell lineage commitment but is also indispensable for later stages in T cell maturation such as the selection of CD4 and CD8 T cells. Thus, Foxn1 function critically choreographs both early and late events in thymic lympho-stromal cross-talk. Foxn1 ChIP-seq and RNA-seq in mouse models of hypofunctional or conditional knock-out of Foxn1 Brief sample descriptions are shown below: Foxn1 ChIP-seq (GSM1945905) - chromatin immunoprecipitated using an antibody against FOXN1-FLAG (wt*); 2 samples Input ChIP-seq (GSM1945906) - input chromatin; 2 samples 42cT (GSM1945907) - RNA-seq on wt*/-::nu/nu cTEC; 3 samples 42mT (GSM1945908) - RNA-seq on wt*/-::nu/nu mTEC; 2 samples 96cT (GSM1945909) - RNA-seq on wt*/wt*::nu/nu cTEC; 3 samples 96mT (GSM1945910) - RNA-seq on wt*/wt*::nu/nu mTEC; 2 samples NcT (GSM1945911) - RNA-seq on Dox-treated TetO- iFoxn1(del7,8) cTEC; 5 samples PcT (GSM1945912) - RNA-seq on Dox-treated TetO+ iFoxn1(del7,8) cTEC; 5 samples C57BL/6 mice (GSM1945913) - ATAC-seq on wild-type cTEC; 1 sample Please see each sample for more detailed information.

2016-08-09 | E-GEOD-75219 | biostudies-arrayexpress

ATAC-seq of wildtype or Dppa2 knockout ESC upon release of the epigenetic editing trigger

Project description:Chromatin accessibility was assayed in wildtype or Dppa2 knockout ESC after 26 days of release of the trigger imposed by epigenetic editing. Samples were collected in two clonal knockout and wildtype lines after sorting at FACS of cells which maintained a repressive Esg1-tdTomato (TOMneg) reporter expression after 26 days of DOX washout (release of the trigger).

2021-11-23 | E-MTAB-10522 | biostudies-arrayexpress

ATAC-seq of ESC or in vitro differentiated endoderm cells after epigenetic editing and upon release of the trigger

Project description:Chromatin accessibility was assayed in ESC after epigenetic editing with dCas9::KRAB (or dCas9::GFP as a control) and subsequently in ESC and Endoderm differentiated cells upon release of the trigger. Samples were collected in two biological replicates after 7 days of DOX induction in ESC (epigenetic editing) and after 7 days of DOX washout (release of the trigger) in ESC and Endoderm cells.

2021-11-23 | E-MTAB-10523 | biostudies-arrayexpress

ChIP-seq of SATB1-bound regions in human ESC-derived dopaminergic (DA) neurons at different time points. ATAC-Seq and RNA-Seq of DA and cortical neurons (WT and SATB1-KO)

Project description:SATB1 is a genetic master regulator in dopaminergic neurons. We try to identify the downstream regulated genes and pathways of SATB1 in human dopaminergic and CTX neurons. The RNA-Seq experiment was performed to investigate the role of the genetic master regulator SATB1 in human dopaminergic neurons in comparison to cortical neurons. We generated a human embryonic stem cell knockout clone for SATB1 and differentiated this clone into either dopaminergic or cortical neurons. Immature dopaminergic (day 30 of differentiation), mature dopaminergic (day 50 of differentiation) and mature cortical neurons (day 30 of differentiation) were subsequently subjected to RNA-Seq. We compared wild type and SATB1-KO neurons at the afore mentioned time points, to characterize the regulatory role of SATB1 in the different neuron subtypes.

2019-09-20 | E-MTAB-5965 | biostudies-arrayexpress

Chromatin accessibility (ATAC-seq) of human acute leukemias and healthy donors

Project description:ATAC-seq of 79 primary samples obtained from human acute leukemias, namely AML, T-ALL and mixed myeloid/lymphoid leukemias with CpG Island Methylator Phenotype (CIMP). Moreover, ATAC-seq of CD34+ HSPCs from 3 healthy donors are included. ATAC-seq was performed as described (Buenrostro et al., 2013) with a modification in the lysis buffer to reduce mitochondrial DNA contamination. Due to patient confidentiality considerations, the raw data files for this dataset have been deposited to the EGA controlled-access archive under the accession numbers EGAS00001007094 (study); EGAD00001011050 (dataset).

2023-08-31 | E-MTAB-13118 | biostudies-arrayexpress

ATAC-Seq using native and iPSC-derived murine retina at three developmental stages.

Project description:To identify epigenetic programs underlying differentiation of mouse retina, we performed ATAC-Seq on bulk native retina (NaR) and iPSC-derived 3D retinal aggregates (3D-RA) at three matched stages of development: embryonic day (E)13 vs differentiation day (DD)13, postnatal day (P)0 vs DD21, and P5 vs DD25. We produced a total of 24 ATAC-seq libraries with two technical replicates (using either 1 ul or 2 ul of TDE1 enzyme) of two biological replicates, and two genomic DNA libraries to use for background controls.

2021-06-30 | E-MTAB-9440 | biostudies-arrayexpress

Open chromatin profiling on ESC transition to day1- and day2-epiblast-like stem cells

Project description:Identification of open chromatin profiles at ESC, d1EpiLC and d2EpiLC. The accessible chromatin landscape of naive ESCs (Rex1GFPd2 mouse embryonic stem cell line; parental line; E14Tg2a) and their transition to EpiLCs over a two day period was determined using ATAC-seq.

2019-05-11 | E-MTAB-7207 | biostudies-arrayexpress

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