Rhabdomyosarcoma can be initiated in activated Pax7+ Muscle Progenitor Cells
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
SUBMITTER: Jeffrey Mito
PROVIDER: E-GEOD-25098 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
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Project description:The cell of origin for rhabdomyosarcoma (RMS) and undifferentiated pleomorphic sarcoma (UPS) remains to be determined. We utilized two skeletal muscle specific inducible Cre mouse lines to transform both skeletal muscle stem cells and progenitors to determine which cells give rise to RMS and UPS. Both P7KP and MDKP derived mice were injected with systemic tamoxifen and mice were euthanized after tumor development. Sections of resected tumor were placed in RNAlater and placed at -80 until RNA isolation. RNA was isolated by grinding up tumor sections in liquid nitrogen and using the Qiagen RNEasy Micro kit.
2013-10-11 | E-GEOD-46836 | biostudies-arrayexpress
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2011-01-30 | GSE25098 | GEO
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
Project description:Our goal was to identify differentially expressed genes in Drosophila muscle when misexpressing the human PAX-FKHR fusion oncoprotein. Using the GAL4-UAS expression system, PAX7-FKHR was misexpressed in differentiating muscle. After 2-3 days of expression larval animals were collected, dissected to remove as much non-muscle internal tissue as possible, mRNA extracted, and expression profiling done with Affy Drosophila 2.0 genome chips
2011-10-26 | E-MTAB-839 | biostudies-arrayexpress
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: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
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 canonical Wnt signaling pathway is critical for myogenesis and can induce muscle progenitors to switch from proliferation to differentiation; how Wnt signals integrate with muscle specific regulatory factors in this process is poorly understood. We previously demonstrated that the Barx2 homeobox protein promotes differentiation in cooperation with the muscle regulatory factor (MRF) MyoD. Pax7, another important muscle homeobox factor represses differentiation. We now identify Barx2,MyoD,and Pax7 as novel components of the Wnt effector complex, providing a new molecular pathway for regulation of muscle progenitor differentiation. Canonical Wnt signaling induces Barx2 expression in muscle progenitors and perturbation of Barx2 leads to misregulation of Wnt target genes. Barx2 activates two endogenous Wnt target promoters as well as the Wnt reporter gene TOPflash, the latter synergistically with MyoD. Moreover, Barx2 interacts with the core Wnt effectors β-catenin and TCF, is recruited to TCF/LEF sites, and promotes recruitment of β-catenin. In contrast, Pax7 represses the Wnt reporter gene and antagonizes the activating effect of Barx2. Pax7 also binds β-catenin suggesting that Barx2 and Pax7 may compete for interaction with the core Wnt effector complex. Overall, the data show for the first time that Barx2, Pax7, and MRFs can act as direct transcriptional effectors of Wnt signals in myoblasts and that Barx2 and Wnt signaling participate in a regulatory loop. We propose that antagonism between Barx2 and Pax7 in regulation of Wnt signaling may help mediate the switch from myoblast proliferation to differentiation. RNA-Seq analyses was used to characterize gene expression in primary myoblasts from wild-type and Barx2 knockout mice.
2015-10-22 | E-GEOD-53398 | biostudies-arrayexpress
Project description:To identify Pax7 target genes in muscle progenitor cells, we compared the transcriptome profiles of muscle progenitor cells from young mice (P12) with and without Pax7.
2017-05-22 | GSE97690 | GEO
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