Pluripotent stem cell-derived myogenic progenitors remodel their molecular signature upon in vivo engraftment [Microarray]
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ABSTRACT:
PROVIDER: PRJNA497869 | ENA |
REPOSITORIES: ENA
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Project description:Optimal cell-based therapies for the treatment of muscle degenerative disorders should not only regenerate fibers, but provide a quiescent satellite cell pool ensuring long-term maintenance and regeneration. Conditional expression of Pax3/Pax7 in differentiating pluripotent stem cells (PSC) allows the generation of myogenic progenitors endowed with satellite cell-like abilities. To identify the molecular determinants underlying their regenerative potential, we performed transcriptome analyses of these cells along with primary myogenic cells from several developmental stages. Here we show that in vitro generated PSC-derived myogenic progenitors possess a molecular signature similar to embryonic/fetal myoblasts. However, compared to fetal myoblasts, following transplantation they show superior myofiber engraftment and ability to seed the satellite cell niche, respond to multiple re-injuries and contribute to long-term regeneration. Upon engraftment, the transcriptome of Pax3/Pax7-induced PSC-derived myogenic progenitors changes dramatically, acquiring similarity to that of satellite cells, particularly in genes involved in extracellular matrix remodeling. Single cell profiling reveals that these changes are induced, not selected, by the in vivo environment. These findings demonstrate that Pax3/Pax7-induced PSC-derived myogenic progenitors possess proliferative and migratory abilities characteristic of earlier developmental stages, and an intrinsic ability to respond to environmental cues upon skeletal muscle regeneration.
2019-02-13 | GSE121615 | GEO
Project description:Pluripotent stem cell-derived myogenic progenitors remodel their molecular signature upon in vivo engraftment
| PRJNA497909 | ENA
Project description:Optimal cell-based therapies for the treatment of muscle degenerative disorders should not only regenerate fibers, but provide a quiescent satellite cell pool ensuring long-term maintenance and regeneration. Conditional expression of Pax3/Pax7 in differentiating pluripotent stem cells (PSC) allows the generation of myogenic progenitors endowed with satellite cell-like abilities. To identify the molecular determinants underlying their regenerative potential, we performed transcriptome analyses of these cells along with primary myogenic cells from several developmental stages. Here we show that in vitro generated PSC-derived myogenic progenitors possess a molecular signature similar to embryonic/fetal myoblasts. However, compared to fetal myoblasts, following transplantation they show superior myofiber engraftment and ability to seed the satellite cell niche, respond to multiple re-injuries and contribute to long-term regeneration. Upon engraftment, the transcriptome of Pax3/Pax7-induced PSC-derived myogenic progenitors changes dramatically, acquiring similarity to that of satellite cells, particularly in genes involved in extracellular matrix remodeling. Single cell profiling reveals that these changes are induced, not selected, by the in vivo environment. These findings demonstrate that Pax3/Pax7-induced PSC-derived myogenic progenitors possess proliferative and migratory abilities characteristic of earlier developmental stages, and an intrinsic ability to respond to environmental cues upon skeletal muscle regeneration.
2019-02-13 | GSE121469 | GEO
Project description:Pluripotent stem cell-derived myogenic progenitors remodel their molecular signature upon in vivo engraftment [RNA-seq]
| PRJNA497477 | ENA
Project description:Optimal cell-based therapies for the treatment of muscle degenerative disorders should not only regenerate fibers but provide a quiescent satellite cell pool ensuring long-term maintenance and regeneration. Conditional expression of Pax3/Pax7 in differentiating pluripotent stem cells (PSCs) allows the generation of myogenic progenitors endowed with enhanced regenerative capacity. To identify the molecular determinants underlying their regenerative potential, we performed transcriptome analyses of these cells along with primary myogenic cells from several developmental stages. Here we show that in vitro-generated PSC-derived myogenic progenitors possess a molecular signature similar to embryonic/fetal myoblasts. However, compared with fetal myoblasts, following transplantation they show superior myofiber engraftment and ability to seed the satellite cell niche, respond to multiple reinjuries, and contribute to long-term regeneration. Upon engraftment, the transcriptome of reisolated Pax3/Pax7-induced PSC-derived myogenic progenitors changes toward a postnatal molecular signature, particularly in genes involved in extracellular matrix remodeling. These findings demonstrate that Pax3/Pax7-induced myogenic progenitors remodel their molecular signature and functionally mature upon in vivo exposure to the adult muscle environment.
| S-EPMC6410870 | biostudies-literature
Project description:This SuperSeries is composed of the SubSeries listed below.
2019-02-13 | GSE121639 | GEO
Project description:Myogenic differentiation of iPSCs has been done by gene–overexpression or directed differentiation. However, viral integration, long-term culture and the presence of unwanted cells are the main obstacles. By using CRISPR/Cas9n, a novel double reporter hESC line was generated for PAX7/MYF5, allowing prospective readout. This strategy allowed pathway screen to define efficient myogenic induction in hESC/iPSCs. Next, surface marker screen allowed identification of CD10 and CD24 for purification of myogenic progenitors. CD10 expression was also confirmed on human satellite cells and muscle progenitors. In vivo studies using transgene/reporter-free hESC/iPSCs further validated myogenic potential of the cells by dystrophin restoration and satellite cell engraftment in NSG-mdx4cv mice. In addition, side-by-side in vitro and in vivo comparison proved superior specificity of CD10/CD24 compared to recently reported markers (ERBB3/NGFR). This study provides new biological insights for myogenic differentiation using a new cell resource and identifies CD10 as a potential myogenic marker.
2018-12-03 | GSE121154 | GEO
Project description:Stem cell transplantation presents a potentially curative strategy for genetic disorders of skeletal muscle, but the application of this approach has been limited due to the deleterious effects of cell expansion in vitro and poor engraftment efficiency. In an effort to overcome this hurdle, we sought to identify molecular signals that enhance the myogenic activity of cultured muscle progenitors. Here, we report the development and application of a cross-species small molecule screening platform employing zebrafish and mouse, which enables rapid, direct evaluation of the effects of chemical compounds on the engraftment of transplanted muscle precursor cells. Using this system, we screened a library of bioactive lipids to identify those that could increase myogenic engraftment in zebrafish and mice. These efforts identified two lipids, lysophosphatidic acid (LPA) and niflumic acid (NFA), both linked to activation of intracellular calcium ion flux, which showed conserved, dose-dependent and synergistic effects in promoting muscle engraftment across these vertebrate species.
2023-01-16 | GSE143801 | GEO
Project description:Zinc finger E-box-binding homeobox 2 (ZEB2, also known as SMAD interacting protein 1 or Zfhx1b) protein is a transcription factor involved in the transforming growth factor β (TGFβ) and bone morphogenetic proteins (BMPs) signaling pathways. ZEB2 is a two-handed zinc-finger closely related to ZEB1 (ZFHX1a/δEF1) and it is present in many tissues including cardiac and skeletal muscles. Skeletal muscle development and adult myogenesis are regulated by helix-loop-helix proteins, including MyoD, Myf5, myogenin and MRF-4. It has been shown that ZEB1 (ZFHX1a/δEF1) competes with the myogenic regulatory factors for their consensus sequences on some target genes during muscle differentiation, however the role of ZEB2 in myogenesis is still unknown. In the present study, we evaluated the myogenic potential of Zeb2-null and R26_Zeb2 mouse embryonic stem cells by single-cell RNA-sequencing and tested muscle engraftment capability of the respective myogenic progenitors. Our results support the implication of Zeb2 in promoting myogenesis in pluripotent stem cells and myogenic progenitors by modulating specific genes encoding components of the TGFβ/BMP signaling system.
2020-03-31 | GSE147744 | GEO
Project description:Here, we transplanted human iPAX7 myogenic progenitors into skeletal muscles of non-dystrophic and dystrophic mice and compared the transcriptional landscape of human donor-derived myofibers with respective in vitro-differentiated iPAX7 myotubes. Pairing bulk RNA sequencing with computational deconvolution of human reads, we were able to pinpoint key myogenic changes that occur during the in vitro-to-in vivo transition, confirm developmental maturity, and consequently further suggest the utility of cell-based therapies.
2024-04-02 | GSE244521 | GEO