Pluripotent stem cell-derived myogenic progenitors remodel their molecular signature upon in vivo engraftment.
Pax3
Pax7
pluripotent stem cell
skeletal myogenesis
transcriptome analysis
Journal
Proceedings of the National Academy of Sciences of the United States of America
ISSN: 1091-6490
Titre abrégé: Proc Natl Acad Sci U S A
Pays: United States
ID NLM: 7505876
Informations de publication
Date de publication:
05 03 2019
05 03 2019
Historique:
pubmed:
15
2
2019
medline:
24
3
2020
entrez:
15
2
2019
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 30760602
pii: 1808303116
doi: 10.1073/pnas.1808303116
pmc: PMC6410870
doi:
Substances chimiques
PAX3 Transcription Factor
0
PAX7 Transcription Factor
0
Pax7 protein, mouse
0
Pax3 protein, mouse
138016-91-8
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
4346-4351Subventions
Organisme : NIAMS NIH HHS
ID : R01 AR055299
Pays : United States
Organisme : NIAMS NIH HHS
ID : R01 AR055685
Pays : United States
Organisme : NIAMS NIH HHS
ID : R01 AR071439
Pays : United States
Organisme : NHLBI NIH HHS
ID : U01 HL100407
Pays : United States
Déclaration de conflit d'intérêts
The authors declare no conflict of interest.
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