Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Pax7 remodels the chromatin landscape in skeletal muscle stem cells

ABSTRACT: The mechanisms by which Pax7 promotes skeletal muscle stem (satellite) cell identity are not yet understood. We have taken advantage of pluripotent stem cells wherein the induced expression of Pax7 robustly initiates the muscle program and enables the generation of muscle precursors that repopulate the satellite cell compartment upon transplantation. Pax7 binding was excluded from H3K27 tri-methylated regions, suggesting that recruitment of this factor is circumscribed by chromatin state. Further, Pax7 binding provoked localized chromatin remodeling, including the acquisition of enhancer-associated histone marks and induction of chromatin accessibility. Conversely, removal of Pax7 led to rapid reversal of these features on a subset of enhancers. Another cohort of Pax7 binding sites exhibited a durably accessible and remodeled chromatin state after Pax7 removal, and persistent enhancer accessibility was associated with subsequent binding by muscle regulatory factors. Our studies provide new insights into Pax7 and the epigenetic landscape of skeletal muscle stem cells.

ORGANISM(S): Mus musculus

PROVIDER: GSE89977 | GEO | 2017/04/26

SECONDARY ACCESSION(S): PRJNA354348

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Identification of Pax7 target genes in muscle stem cells

Project description:Adult muscle stem cells, also known as muscle satellite cells, which are the resident tissue stem cells of skeletal muscle, provide myonuclei for postnatal muscle growth and for maintenance and regeneration in adults. Satellite cells specifically express the transcription factor pax7. The purpose of this study was to identify pax7 target genes and clarify the role of pax7 in muscle stem cell maintenance. We succeeded in generating Pax7-YFP knockin mice (Pax7-YFP KI) that can visualize endogenous pax7 expressed in satellite cells with YFP fluorescent protein. Novel pax7 target genes were identified by ChIP-sequencing (chromatin immunoprecipitation) analysis with muscle stem cells of Pax7-YFP KI mice.

2023-08-31 | GSE164535 | GEO

Gene expression response to Pax7 in murine myoblasts

Project description:Pax7 is a paired box transcription factor that is central to skeletal muscle satellite cell function Microarrays were used to examine gene expression after primary murine satellite cell-derived myoblasts were retrovirally infected with constructs encoding Pax7, PAX7-FOXO1A, dominant negative Pax7-ERD and retroviral control.

2017-02-01 | GSE77478 | GEO

Direct reprogramming of mouse fibroblasts into functional skeletal muscle progenitors

Project description:Skeletal muscle harbors quiescent stem cells termed satellite cells and proliferative progenitors termed myoblasts, which play pivotal roles during muscle regeneration. However, current technology does not allow permanent capture of these cell populations in vitro. Here, we show that ectopic expression of the myogenic transcription factor MyoD, combined with exposure to small molecules, reprograms mouse fibroblasts into expandable induced myogenic progenitor cells (iMPCs). iMPCs express key skeletal muscle stem and progenitor cell markers including Pax7 and Myf5 and give rise to Dystrophin-expressing myofibers upon transplantation, a subset of which maintain Pax7 expression in vivo and sustain serial regenerative responses. Similar to satellite cells, iMPCs originate from Pax7+ cells and require Pax7 itself for maintenance. Finally, we show that iMPCs can be established from muscle tissue following small molecule exposure alone. This study thus reports on a robust approach to derive expandable myogenic stem/progenitor-like cells from multiple differentiated cell types.

2018-05-01 | GSE92336 | GEO

Direct reprogramming of mouse fibroblasts into functional skeletal muscle progenitors

2018-05-01 | GSE108543 | GEO

Expression profiling of type II skeletal muscle fibers from wild-type mice, myofiber-specific and satellite cell-specific Rrm2b knockout models

Project description:RNA-seq was performed to investigate the role of Rrm2b in skeletal muscle. Type II skeletal muscle fibers were collected from wild-type (C57BL/6) mice and two Rrm2b knockout models, the skeletal muscle-specific knockout (Rrm2b F/F;HSA-Cre, smKO) and satellite cell-specific knockout (Rrm2b F/F;Pax7-CreERT2, scKO).

2022-07-25 | E-MTAB-11318 | biostudies-arrayexpress

Human muscle-derived CLEC14A-positive cells regenerate muscle independent of PAX7

Project description:Skeletal muscle stem cells, called satellite cells, are responsible for postnatal muscle growth, homeostasis and regeneration. Attempts to utilize the regenerative potential of muscle stem cells for therapeutic purposes so far failed. The transcription factor Pax7 defines satellite cells across species 1-4 . We previously established human PAX7-positive cell colonies with high regenerative potential 5 . We now identified PAX7-negative human muscle-derived cell colonies (PAX7neg) also positive for the myogenic markers desmin and MYF5. These included cells from a unique myopathic patient with rigid spine and respiratory insufficiency due to a homozygous PAX7 c.86-1G>A mutation (PAX7null). Single cell and bulk transcriptome analysis showed high intra- and inter-donor heterogeneity and revealed the endothelial cell marker CLEC14A to be highly expressed in PAX7null cells. All PAX7neg cell populations, including PAX7null, formed myofibers after transplantation into mice, and regenerated muscle after reinjury. Transplanted PAX7neg cells repopulated the satellite cell niche where they re-expressed PAX7. Strikingly, PAX7null cells expressing CLEC14A were also identified below the basal lamina. In summary, transplanted human cells do not depend on PAX7 for muscle regeneration. Thus, Pax7 is not a suitable marker for selection of optimal cells for muscle regenerative therapies.

2019-11-11 | GSE117382 | GEO

Muscle progenitor specification and myogenic differentiation are associated with changes in chromatin topology

Project description:Using Hi-C, promoter-capture Hi-C (pCHi-C), and other genome-wide approaches in skeletal muscle progenitors that inducibly express a master transcription factor, Pax7, we systematically characterized at high-resolution the spatio-temporal re-organization of compartments and promoter-anchored interactions as a consequence of myogenic commitment and differentiation. To further investigate transcriptional regulatory mechanisms governed by Pax7, we used immuno-affinity purification and mass spectrometric sequencing to identify the compendium of Pax7-associated proteins in muscle progenitors. Although Pax7-associated proteins have been identified in myoblasts, it is likely that such an approach would fail to uncover progenitor specific interactions with this protein. We therefore isolated chromatin from iPax7 cells engineered with a single, inducible copy of the Flag-tagged Pax7 transgene integrated next to the Hprt locus, which is expected to maintain expression levels comparable to those of satellite cells in the presence of Dox. Through purification of Flag-Pax7, we identified a cohort of factors and complexes involved in gene activation or repression and remodeling of chromatin and genome architecture that were substantially enriched compared to the uninduced control. We also identified a large cohort of sequence-specific TFs, including several that were shown to play an essential role in muscle stem cells (e.g., Foxk1, Six1, Runx1, Tead1, Nfix) and that are recruited to Pax7-bound enhancers in muscle cells. Importantly, we also confirmed multiple interactions from our proteomic screen through immunoprecipitation and western blotting.

2020-10-30 | MSV000086392 | MassIVE

Expression data from skeletal muscle satellite cells at different development stages

Project description:Satellite cells are responsible for the long-term regenerative capacity of adult skeletal muscle. The diminished muscle performance and regenerative capacity of aged muscle is thought to reflect progressive fibrosis and atrophy. Whether this reduction in muscle competency also involves a diminishment in the intrinsic regulation of satellite cell self-renewal remains unknown. We used microarray to identify gene expression changes underlying the marked reduction in the capacity of satellite cells to self-renew, contribute to regeneration and repopulate the niche as they age. Skeletal muscles from heterozygous Pax7-ZsGreen mice were isolated at defined stages: E17.5 (fetal - whole forelimb and hindlimb), postnatal day 21 (adolescent - hindlimb), 2-3 month old (young adult - hindlimb) and >1 year old (older adult - hindlimb) mice. ZsGreen-positive skeletal muscle satellite cells were isolated by FACS and pooled (fetal n=4, adolescent n=6, young adult n=8 and older adult n=8 mice).

2014-05-26 | E-GEOD-47401 | biostudies-arrayexpress

Acetylation of PAX7 Controls Muscle Stem Cell Self-Renewal and Differentiation Potential

Project description:It has been suggested that muscle stem cell function is regulated by Acetyl-CoA and NAD+ availability, but the mechanisms remain unclear. We identified two acetylation sites on PAX7 that positively regulate its transcriptional activity. Lack of PAX7 acetylation reduces DNA binding, specifically to the homeobox motif. The acetyltransferase MYST1 stimulated by Acetyl-CoA, and the deacetylase SIRT2 stimulated by NAD+, were identified as direct regulators of PAX7 acetylation and asymmetric division in muscle stem cells. Abolishing PAX7 acetylation in mice using CRISPR/Cas9 mutagenesis led to an expansion of the satellite stem cell pool, reduced numbers of asymmetric stem cell divisions, and increased numbers of oxidative IIA myofibers. Gene expression analysis confirmed that lack of PAX7 acetylation preferentially affects the expression of target genes regulated by homeodomain binding motifs. Thus, PAX7 acetylation status regulates muscle stem cell function and differentiation potential to facilitate metabolic adaptation of muscle tissue.

2021-05-03 | GSE167532 | GEO

Gene expression profiles in skeletal muscle satellite cells lacking Dnmt1

Project description:To identify the target genes of Dnmt1 in skeletal muscle satellite cells, we generated satellite cell specific Dnmt1 KO using Pax7-CreERT2 and Dnmt1 flox mice. After Tamoxifen (cKO) or vehicle (Control) treatment for 5 consecutive days, mice were euthanized and muscle satellite cells were collected by FACS sorting and total RNA were extracted.

2021-01-08 | GSE156978 | GEO

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

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