Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

RNA-sequencing analysis of differential expression in supt16h mutants

ABSTRACT: Haematopoietic stem cells (HSCs) have long been the focus of developmental and regenerative studies, yet our understanding of the signalling events regulating their specification remains incomplete. We demonstrate that supt16h, a component of the FAcilitates Chromatin Transcription (FACT) complex, is required for HSC formation. Zebrafish supt16h mutants express reduced levels of Notch signalling components, genes essential for HSC development, due to abrogated transcription. Classically, Supt16h regulates transcription and nucleosome reorganization. Whereas global chromatin accessibility in supt16h mutants is unaffected, we observe a specific increase in accessibility at the p53 locus, causing an accumulation of p53 mRNA and protein. We further demonstrate that P53 levels directly influence expression of the Polycomb Group protein, phc1, which functions as a transcriptional repressor of Notch genes. Suppression of phc1 or its upstream regulator, p53, rescues both loss of Notch and loss of HSC phenotypes in supt16h mutants. Taken together, our results highlight a previously uncharacterized relationship between supt16h, p53, and phc1 to specify HSCs via modulation of Notch signalling.

ORGANISM(S): Danio rerio

PROVIDER: GSE127555 | GEO | 2020/09/01

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Similar Datasets

P53 based ChIP-sequencing of wildtype and mutant supt16h-/- zebrafish

Project description:Hematopoietic stem cells (HSCs) have long been the focus of developmental and regenerative studies, yet our understanding of the signaling events regulating their specification remains incomplete. We demonstrate that supt16h, a component of the FAcilitates Chromatin Transcription (FACT) complex, is required for HSC formation. Zebrafish supt16h mutants express reduced levels of Notch signaling components, genes essential for HSC development, due to abrogated transcription. Classically, Supt16h regulates transcription and nucleosome reorganization. Whereas global chromatin accessibility in supt16h mutants is unaffected, we observe a specific increase in accessibility at the p53 locus, causing an accumulation of p53 mRNA and protein. We further demonstrate that P53 levels directly influence expression of the Polycomb Group protein, phc1, which functions as a transcriptional repressor of Notch genes. Suppression of phc1 or its upstream regulator, p53, rescues both loss of Notch and loss of HSC phenotypes in supt16h mutants. Taken together, our results highlight a previously uncharacterized relationship between supt16h, p53, and phc1 to specify HSCs via modulation of Notch signaling.

2020-09-01 | GSE116088 | GEO

Comparative chromatin accessibility profiling of wildtype and supt16h-/- zebrafish using ATAC-sequencing

Project description:Chromatin organization and accessibility are fundamental to how genes are transcriptionally controlled. We identify the first vertebrate mutant for supt16h, a component of the FACT (FAcilitates Chromatin Transcription) complex along with Ssrp1 known to reorganize nucleosomes and assist in transcriptional elongation. We demonstrate its importance in hematopoietic stem cell (HSC) specification by regulating the elongation of Notch genes. Unexpectedly, Assay for Transposase Accessible Chromatin (ATAC) sequencing revealed that loss of supt16h does not affect histone accessibility on a Notch-specific or global level. Although the majority of genes are unaffected, loss of supt16h alters chromatin accessibility significantly at the p53 locus, leading to its overexpression in mutants. Upon downregulation of p53, both loss of Notch and loss of HSC phenotypes are rescued. Notably, ssrp1 mutants possessed normal elongation of Notch genes, levels of P53, and specification of HSCs. Our results highlight the discrete effects of Supt16h and Ssrp1 during HSC specification. Additionally, we demonstrate the relationship between supt16h and p53 during transcriptional elongation to specify HSC fate via modulation of Notch signaling.

2020-09-01 | GSE106341 | GEO

RNA-sequencing based linkage analysis identifies supt16h as a target gene from a forward genetic screen

2020-09-01 | GSE106342 | GEO

Single Cell RNA-Sequencing using smart-seq2 of young and old murine hematopoietic stem cells

Project description:Ageing of the hematopoietic stem cell (HSC) compartment is characterized by skewing towards the myeloid lineage and reduced stem cell function, the molecular basis of which is largely unknown. Using single cell approaches we identify features contributing to HSC exhaustion with age. A distinct subpopulation of old HSCs carried a signature indicative of impaired stem cell function, activating p53 targets involved in senescence. In the same HSCs, we identified pro-proliferative JAK/STAT and MAPK signalling. We hypothesized that prolonged proliferation of HSCs leads to cell cycle arrest with age and therefore challenged HSCs with a constant proliferative stimulus mediated by a constitutively active form of Jak2, Jak2V617F. Indeed we observed expansion of the p53 positive population and functional impairment of the challenged HSCs. Our results reveal unexpected heterogeneity in the rate of HSC ageing and strongly implicate a role for proliferation in the p53 mediated functional decline of old HSCs.

2017-05-22 | GSE87631 | GEO

RNA-sequencing analysis of differential expression in supt16h mutants

Project description:RNA-sequencing analysis of differential expression in supt16h mutants

| PRJNA524919 | ENA

Cis inhibition of NOTCH1 through JAGGED1 sustains embryonic Hematopoietic stem cell fate [scRNA-seq]

Project description:Hematopoietic stem cells (HSCs) develop from the hemogenic endothelium (HE) in the aorta- gonads-and mesonephros (AGM) region and reside within Intra-aortic hematopoietic clusters (IAHC) along with hematopoietic progenitors (HPC). The signalling mechanisms that distinguish HSCs from HPCs are unknown. Notch signaling is essential for arterial specification, IAHC formation and HSC activity, but current studies on how Notch segregates these different fates are inconsistent. We now demonstrate that Notch activity is highest in a subset of, GFI1+, HSC-primed HE cells, and is gradually lost with HSC maturation. We uncover that the HSC phenotype is maintained due to increasing levels of NOTCH1 and JAG1 interactions on the surface of the same cell (cis) that renders the NOTCH1 receptor from being activated. Forced activation of the NOTCH1 receptor in IAHC activates a hematopoietic differentiation program. Our results indicate that NOTCH1-JAG1 cis-inhibition preserves the HSC phenotype in the hematopoietic clusters of the embryonic aorta.

2024-01-22 | GSE230792 | GEO

Cis inhibition of NOTCH1 through JAGGED1 sustains embryonic Hematopoietic stem cell fate [RNA-seq]

2024-01-22 | GSE230790 | GEO

P53 based ChIP-sequencing of wildtype and mutant supt16h-/- zebrafish

Project description:P53 based ChIP-sequencing of wildtype and mutant supt16h-/- zebrafish

| PRJNA476997 | ENA

Aspp1 Preserves Hematopoietic Stem Cell Pool Integrity and Prevents Malignant Transformation

Project description:Quiescent hematopoietic stem cells (HSCs) are prone to mutagenesis, and accumulation of mutations can result in hematological malignancies. The mechanisms through which HSCs prevent such detrimental accumulation, however, are unclear. Here, we show that Aspp1 coordinates with p53 to maintain the genomic integrity of the HSC pool. Aspp1 is preferentially expressed in HSCs and restricts HSC pool size by attenuating self-renewal under steady state conditions. After genotoxic stress, Aspp1 promotes HSC cycling and induces p53-dependent apoptosis in cells with persistent DNA damage foci. Beyond these p53-dependent functions, Aspp1 attenuates HSC self-renewal and accumulation of DNA damage in p53-null HSCs. Consequently, concomitant loss of Aspp1 and p53 leads to the development of hematological malignancies, especially T-cell leukemia and lymphoma. Together, these data highlights coordination between Aspp1 and p53 in regulating HSC self-renewal and DNA damage tolerance, and suggest that HSCs possess specific mechanisms that prevent accumulation of mutations and malignant transformation. 8-week-old WT, Aspp1-/-, Mx1-Cre(+)p53flox/flox and Mx1-Cre(+)Aspp1-/-p53flox/flox mice were intraperitoneally administered with 400 μg pIpC five times every other day to obtain WT, Aspp1-/-, p53-/- and Aspp1-/-p53-/- bone marrow. 4 weeks after pIpC treatment, bone marrow lineage(-) Sca-1(+) cKit(+) cells were isolated. RNA was extracted and pooled from 3 independent mice per genotype. RNA samples were then amplified, labeled, and hybridized to independent arrays.

2015-05-20 | E-GEOD-69032 | biostudies-arrayexpress

Aspp1 Preserves Hematopoietic Stem Cell Pool Integrity and Prevents Malignant Transformation

2015-05-20 | GSE69032 | GEO

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