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| Status |
Public on Feb 13, 2019 |
| Title |
Pluripotent stem cell-derived myogenic progenitors remodel their molecular signature upon in vivo engraftment [Microarray] |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by array
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| Summary |
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.
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| Overall design |
Three replicates of each sample (iPax3 and iPax7 mononucleated cells) were analyzed and compared to reference developmental samples adult satellite cells (three rep each). Transcriptome profiling of iPax3/7 cells injected in vivo and re-isolated was then compared to adult satellite cells (3 reps each).
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| Contributor(s) |
Incitti T, Darabi R, Ce Y, Perlingeiro RC |
| Citation(s) |
30760602, 32493438 |
| |
| Submission date |
Oct 22, 2018 |
| Last update date |
Jun 16, 2020 |
| Contact name |
Tania Incitti |
| E-mail(s) |
tincitti@umn.edu
|
| Organization name |
University of Minnesota
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| Street address |
2231 6th Street SE
|
| City |
Minneapolis |
| State/province |
Minnesota |
| ZIP/Postal code |
55455 |
| Country |
USA |
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| Platforms (1) |
| GPL4134 |
Agilent-014868 Whole Mouse Genome Microarray 4x44K G4122F (Feature Number version) |
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| Samples (9)
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| This SubSeries is part of SuperSeries: |
| GSE121639 |
Pluripotent stem cell-derived myogenic progenitors remodel their molecular signature upon in vivo engraftment |
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| Relations |
| BioProject |
PRJNA497869 |
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