Identification of Pax7 target genes in muscle progenitor cells from young mice
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE97690 | GEO | 2017/05/22
SECONDARY ACCESSION(S): PRJNA382676
REPOSITORIES: GEO
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Project description:Microarray analysis of rhabdomyosarcomas generated using mice with conditional mutations in Kras and p53 using both in vivo and in vitro approaches to identify a cell of origin for rhabdomyosarcoma. Contains rhabdomyosarcomas derived in vivo using Pax7-CreER mice and in vitro using sorted muscle progenitor cells, UPS derived from intramuscular Adeno-Cre injection, and normal muscle.
2011-01-30 | E-GEOD-25098 | biostudies-arrayexpress
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.
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Project description:Global gene expression patterns were determined from microarray results from sham surgery or following 1 week of plantaris muscle hypertrophy induced by synergist ablation in young adult Pax7-DTA mice (4 months). Vehicle treated mice have their full complement of satellite cells; tamoxifen treated mice have had their satellite cells genetically depleted through Cre-loxP technology
2014-02-20 | GSE52597 | GEO
Project description:Global gene expression patterns were determined from microarray results from sham surgery or following 1 week of plantaris muscle hypertrophy induced by synergist ablation in young adult Pax7-DTA mice (4 months). Vehicle treated mice have their full complement of satellite cells; tamoxifen treated mice have had their satellite cells genetically depleted through Cre-loxP technology After sham surgery or 1 week of overload, Affymetrix chips (mouse430_2.0) were used with 1 µg of total RNA derived from a pooled sample of the right and left plantaris muscles from 11 animals.
2014-02-20 | E-GEOD-52597 | biostudies-arrayexpress
Project description:Muscle stem cells (MuSC) change molecular and functional properties during development. Using a transgenic Tg:Pax7-nGFP mice, we FACS-isolated MuSC from embryonic (E12.5) and foetal (E17.5) stages to understand the differences and similarities amongst the myogenic stem/progenitor populations. Pax7-nGFP+ cells were isolated by FACS from limb buds of E12.5 and E17.5 Tg:Pax7-nGFP embryos following enzymatic digestion. Affymetrix microarrays were performed on biological triplicates.
2013-11-08 | E-GEOD-52192 | biostudies-arrayexpress
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
Project description: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.
2017-04-26 | GSE89977 | GEO
Project description:Identification of Pax7 target genes in muscle stem cells
| PRJNA691079 | ENA
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
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