Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

NFI Transcription Factors Govern Stem Cell Chromatin Accessibility and Guard Against Irreversible Hair Loss [ATAC-seq]

ABSTRACT: Tissue homeostasis and regeneration rely upon resident stem cells (SCs), whose behavior is regulated through niche-dependent crosstalk. The mechanisms underlying SC maintenance are still unfolding. Here, using hair follicles (HFs) as model and spatiotemporal gene ablation in mice, we uncover transcription factors (TFs) NFIB and NFIX as guardians of the process. Complete NFI ablation causes SC depletion and hair loss which resembles irreversible alopecia in humans, who intriguingly also display reduced NFI. Through single cell transcriptomics, ATAC- and ChIP-seq profiling, we uncover a key role for NFIB/NFIX in governing chromatin accessibility of HFSC master TFs . When NFIB/NFIX are genetically removed, the stemness epigenetic landscape is lost, as enhancers driving HFSC identity are decommissioned and those of epidermal differentiation and wound-repair are de-repressed. Together, our findings expose NFIB/NFIX as crucial rheostats of tissue homeostasis, functioning to safeguard the SC epigenome from a breach in lineage confinement that otherwise triggers irreversible tissue degeneration.

ORGANISM(S): Mus musculus

PROVIDER: GSE135144 | GEO | 2020/04/01

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Similar Datasets

NFI Transcription Factors Govern Stem Cell Chromatin Accessibility and Guard Against Irreversible Hair Loss [ChIP-seq]

Project description:Tissue homeostasis and regeneration rely upon resident stem cells (SCs), whose behavior is regulated through niche-dependent crosstalk. The mechanisms underlying SC maintenance are still unfolding. Here, using hair follicles (HFs) as model and spatiotemporal gene ablation in mice, we uncover transcription factors (TFs) NFIB and NFIX as guardians of the process. Complete NFI ablation causes SC depletion and hair loss which resembles irreversible alopecia in humans, who intriguingly also display reduced NFI. Through single cell transcriptomics, ATAC- and ChIP-seq profiling, we uncover a key role for NFIB/NFIX in governing chromatin accessibility of HFSC master TFs . When NFIB/NFIX are genetically removed, the stemness epigenetic landscape is lost, as enhancers driving HFSC identity are decommissioned and those of epidermal differentiation and wound-repair are de-repressed. Together, our findings expose NFIB/NFIX as crucial rheostats of tissue homeostasis, functioning to safeguard the SC epigenome from a breach in lineage confinement that otherwise triggers irreversible tissue degeneration.

2020-04-01 | GSE135145 | GEO

NFI Transcription Factors Govern Stem Cell Chromatin Accessibility and Guard Against Irreversible Hair Loss [scRNA-seq]

2020-04-01 | GSE135143 | GEO

NFI Transcription Factors Govern Stem Cell Chromatin Accessibility and Guard Against Irreversible Hair Loss [bulk RNA-seq]

2020-04-01 | GSE135142 | GEO

Common regulatory targets of NFIA, NFIX and NFIB during postnatal cerebellar development

Project description:Transcriptional regulation plays a central role in controlling neural stem and progenitor cell proliferation and differentiation during neurogenesis. For instance, transcription factors from the nuclear factor I (NFI) family have been shown to co-ordinate neural stem and progenitor cell differentiation within multiple regions of the embryonic nervous system, including the neocortex, hippocampus, spinal cord and cerebellum. Knockout of individual Nfi genes culminates in similar phenotypes, suggestive of common target genes for these transcription factors. However, whether or not the NFI family regulates common suites of genes remains poorly defined. Here, we use granule neuron precursors (GNPs) of the postnatal murine cerebellum as a model system to analyse regulatory targets of three members of the NFI family: NFIA, NFIB and NFIX. By integrating transcriptomic profiling (RNA-seq) of Nfia- and Nfix-deficient GNPs with epigenomic profiling (ChIP-seq against NFIA, NFIB and NFIX, and DNase I hypersensitivity assays), we reveal that these transcription factors share a large set of potential transcriptional targets, suggestive of complementary roles for these NFI family members in promoting neural development.

2020-03-12 | GSE146793 | GEO

The NFIB/CARM1 Partnership is a Therapeutic Target for Small Cell Lung Cancer

Project description:This project identified NFI family members as CARM1 substrates. NFIB was previously reported to play a critical role in the development of small cell lung cancer. We provided evidence that the arginine methylation of NFIB is required for its oncogenic function in small cell lung cancer.

2023-02-07 | PXD038237 | Pride

Nfix is a novel regulator of murine hematopoietic stem and progenitor cell survival

Project description:Hematopoietic stem cells are both necessary and sufficient to sustain the complete blood system of vertebrates. Here we show that Nfix, a member of the nuclear factor I (Nfi) family of transcription factors, is highly expressed by hematopoietic stem and progenitor cells (HSPC) of murine adult bone marrow. Although shRNA mediated knockdown of Nfix expression in Lineage-Sca-1+c-Kit+ HSPC had no effect on in vitro cell growth or viability, Nfix-depleted HSPC displayed a significant loss of colony forming potential, as well as short- and long-term in vivo hematopoietic repopulating activity. Analysis of recipient mice 4-20 days post-transplant revealed that Nfix-depleted HSPC establish in the bone marrow but fail to persist due to increased apoptotic cell death. Gene expression profiling of Nfix-depleted HSPC reveals that loss of Nfix expression in HSPC is concomitant with a decrease in the expression of multiple genes known to be important for HSPC survival, such as Erg, Mecom, Mpl and Prdm16. These data reveal that Nfix is a novel regulator of HSPC survival post-transplantation and establish, for the first time, a role for Nfi genes in the regulation of this cellular compartment. 3 NFIX depleted samples are compared to 3 wt samples

2013-09-05 | E-GEOD-45492 | biostudies-arrayexpress

Epigenomic profiling of hair follicle stem cells identifies PRDM16 as a regulator of sebaceous gland homeostasis [RNA-seq]

Project description:The epidermis consists of different compartments such as the hair follicle (HF), sebaceous gland (SG) and interfollicular epidermis (IFE), each containing distinct stem cell (SC) populations. However, with the exception of the SCs residing within the HF bulge, other epidermal SC populations remain poorly characterized at the molecular level. Here we used an epigenomic strategy that combines H3K27me3 ChIP-seq and RNA-seq profiling to identify major regulators of HFSC located outside the bulge. When applied to the bulk of HFSC isolated from mouse skin our approach identified both previously known and potentially novel non-bulge HFSC regulators. Among the latter, we found that PRDM16 was preferentially expressed within the Junctional Zone (JZ). To investigate PRDM16 function within the JZ SCs, we generated an epidermal-specific Prdm16 Knock-out mouse model (K14-Cre-Prdm16fl/fl). Notably, although these K14-Cre-Prdm16fl/fl mice did not show any major skin or hair abnormalities, the homeostasis of the SG was clearly compromised. Namely, PRDM16 deficient mice displayed enlarged SGs and excessive sebum production, thus resembling some of the features associated with certain human conditions (i.e. acne, sebaceous hyperplasia). Overall, our study provides a list of putative novel regulators of HFSC outside the bulge and identifies PRDM16 as a major regulator of SG homeostasis.

2021-03-26 | GSE169648 | GEO

Epigenomic profiling of hair follicle stem cells identifies PRDM16 as a regulator of sebaceous gland homeostasis [ChIP-seq]

2021-03-26 | GSE169647 | GEO

Nfix is a novel regulator of murine hematopoietic stem and progenitor cell survival

2013-09-05 | GSE45492 | GEO

Niche stiffening compromises stem cell potential during aging by reducing chromatin accessibility at bivalent promoters

Project description:Tissue homeostasis and regeneration require activation and subsequent lineage commitment of tissue-resident stem cells (SCs). These state changes are controlled by epigenetic barriers. Using hair follicle stem cells (HFSCs) as paradigm, we studied how aging impacts the chromatin landscape and function of mammalian SCs. Analyses of genome-wide chromatin accessibility revealed that aged HFSCs displayed widespread reduction of chromatin accessibility specifically at key SC self-renewal and differentiation genes that were characterized by bivalent promoters carrying both activating and repressive chromatin marks. Consistently, aged HFSCs showed reduced self-renewing capacity and attenuated ability to activate expression of these bivalent genes upon regeneration. These functional defects were niche-dependent as transplantation of aged HFSCs into young recipients or into ex vivo niches restored SC functions and transcription of poised genes. Mechanistically, aged HFSC niche displayed wide-spread alterations in extracellular matrix composition and mechanics, resulting in compressive forces on SCs and subsequent transcriptional repression, leading to loss of bivalent promoters. Tuning tissue mechanics both in vivo and in vitro recapitulated age-related SC changes, implicating niche mechanics as a central regulator of genome organization and function leading to age-dependent SC exhaustion.

2021-05-07 | PXD018352 | Pride

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data