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Expression data from Pax7+ satellite cell derived tumors in vitro and in vivo

ABSTRACT: Mouse muscle stem cells, defined as Pax7+ satellite cells, can initiate rhabdomyosarcoma when transformed by oncogenic Kras and concomitant loss of p53. Mouse Pax7+ satellite cells were transformed in vitro and in vivo utilizing the Cre-ER/loxp system.

ORGANISM(S): Mus musculus

PROVIDER: GSE22798 | GEO | 2011/06/01

SECONDARY ACCESSION(S): PRJNA127825

REPOSITORIES: GEO

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Expression data from Pax7+ satellite cell derived tumors in vitro and in vivo

Project description:Mouse muscle stem cells, defined as Pax7+ satellite cells, can initiate rhabdomyosarcoma when transformed by oncogenic Kras and concomitant loss of p53. Mouse Pax7+ satellite cells were transformed in vitro and in vivo utilizing the Cre-ER/loxp system. We wanted to address two major questions: do the in vitro and in vivo tumors cluster together compared to another mouse to another mouse derived soft-tissue sarcoma AND which human soft-tissue sarcoma do the in vivo derived tumors resemble transcriptionally? Therefore, tumors from cells transformed in vitro and tumors from mice that restrict the oncogenic lesions to Pax7+ satellite cells in vivo were compared to answer these two questions.

2011-06-01 | E-GEOD-22798 | biostudies-arrayexpress

Expression data during plantaris muscle hypertrophy with/without satellite cells induced by synergist ablation in young adult Pax7-DTA mice

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 Âµg 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

Expression data during plantaris muscle hypertrophy with/without satellite cells induced by synergist ablation in young adult Pax7-DTA mice

2014-02-20 | GSE52597 | GEO

Rhabdomyosarcoma can be initiated in activated Pax7+ Muscle Progenitor Cells

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

Differentiation of the human PAX7-positive myogenic precursors/satellite cell lineage in vitro

Project description:Satellite cells (SC) are muscle stem cells which can regenerate adult muscles upon injury. Most SC originate from PAX7+ myogenic precursors set aside during development. Although myogenesis has been studied in mouse and chicken embryos, little is known about human muscle development. Here, we report the generation of human induced pluripotent stem cell (iPSC) reporter lines in which fluorescent proteins have been introduced into the PAX7 and MYOG loci. We use single cell RNA sequencing to analyze the developmental trajectory of the iPSC-derived PAX7+ myogenic precursors. We show that the PAX7+ cells generated in culture can produce myofibers and self-renew in vitro and in vivo. Together, we demonstrate that cells exhibiting characteristics of human fetal satellite cells can be produced in vitro from iPSC, opening interesting avenues for muscular dystrophy cell therapy. This work provides significant insights into the development of the human myogenic lineage.

2020-06-15 | GSE149451 | 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

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

Loss of CRY2 promotes regenerative myogenesis by enhancing PAX7 expression and satellite cell proliferation

Project description:Skeletal muscle has remarkable capacity to regenerate upon injury due to the presence of satellite cells. The maintenance and function of satellite cells are regulated by circadian clock. Cryptocrhome 2 (CRY2) is a key component of the circadian clock and its role in skeletal muscle regeneration remains controversial. Here, we report that CRY2 is down-regulated during muscle regeneration. Using the satellite cell specific CRY2 knockout mice (CRY2scko), we show that deletion of CRY2 enhances muscle regeneration. Single myofiber analysis showed that deletion of CRY2 enhances satellite cell self-renewal. In the absence of CRY2, the ERK1/2 and JNK1/2 signaling pathways become activated, which phosphorylates the transcription factor ETS1, which in turn binds to the promoter of PAX7 to induce its transcription. CRY2 deficient myoblasts survived better in ischemic muscle. Deletion of CRY2 also alleviated myopathy in mdx mice. Therefore, CRY2 plays an essential role in regulating satellite cell function and skeletal muscle regeneration.

2024-04-07 | GSE171651 | GEO

Pax7 remodels the chromatin landscape in skeletal muscle stem cells

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

Divergent transcriptional and transforming properties of PAX3-FOXO1 and PAX7-FOXO1 paralogs

Project description:Hallmarks of the alveolar subclass of Rhabdomyosarcoma are chromosomal translocations that generate PAX3-FOXO1 or PAX7-FOXO1 chimeric transcription factors. Both PAX-FOXO1s drive related cell transformation in animal models, yet the two mutations are associated with distinct pathological manifestations in patients. To evaluate the mechanisms underlying these differences, we generated isogenic fibroblast lines expressing either PAX-FOXO1 paralog. Mapping their genome recruitment using CUT&Tag revealed that the two chimeric proteins have distinct DNA binding preferences. Furthermore, PAX7-FOXO1 causes stronger de novo transactivation of its bound regions than PAX3-FOXO1, resulting in greater transcriptomic dynamics involving genes regulating cell shape and cycle. Consistently, PAX3-FOXO1 accentuates fibroblast cellular traits associated with contractility and surface adhesion and limits entry to M phase. Instead, PAX7-FOXO1 pushes cells to adopt an amoeboid-like shape, reduce S phase entry and provokes more genome instabilities. Altogether, our results demonstrate that PAX7-FOXO1 has a greater chromatin remodelling and transactivating abilities and is more deleterious to cells than PAX3-FOXO1. Altogether our results argue that the diversity in rhabdomyosarcoma manifestation stems, in part, from the diverging transcriptional activity of PAX3-FOXO1 and PAX7-FOXO1. Furthermore, PAX7-FOXO1 pronounced deleterious effects provides an explanation for the low frequency of the translocation generating this factor in Rhabdomyosarcoma patients.

2021-08-15 | GSE180919 | GEO

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