The adult environment promotes the transcriptional maturation of human iPSC-derived muscle grafts.
Journal
NPJ Regenerative medicine
ISSN: 2057-3995
Titre abrégé: NPJ Regen Med
Pays: United States
ID NLM: 101699846
Informations de publication
Date de publication:
04 Apr 2024
04 Apr 2024
Historique:
received:
30
10
2023
accepted:
26
03
2024
medline:
5
4
2024
pubmed:
5
4
2024
entrez:
4
4
2024
Statut:
epublish
Résumé
Pluripotent stem cell (PSC)-based cell therapy is an attractive option for the treatment of multiple human disorders, including muscular dystrophies. While in vitro differentiating PSCs can generate large numbers of human lineage-specific tissue, multiple studies evidenced that these cell populations mostly display embryonic/fetal features. We previously demonstrated that transplantation of PSC-derived myogenic progenitors provides long-term engraftment and functional improvement in several dystrophic mouse models, but it remained unknown whether donor-derived myofibers mature to match adult tissue. Here, we transplanted iPAX7 myogenic progenitors into muscles of non-dystrophic and dystrophic mice and compared the transcriptional landscape of human grafts with respective in vitro-differentiated iPAX7 myotubes as well as human skeletal muscle biospecimens. 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 evaluate their applicability for cell-based therapies.
Identifiants
pubmed: 38575647
doi: 10.1038/s41536-024-00360-4
pii: 10.1038/s41536-024-00360-4
doi:
Types de publication
Journal Article
Langues
eng
Pagination
16Subventions
Organisme : NIAMS NIH HHS
ID : R01 AR078571
Pays : United States
Organisme : NIAMS NIH HHS
ID : R01 AR078624
Pays : United States
Organisme : NIAMS NIH HHS
ID : R01 AR081882
Pays : United States
Organisme : NHLBI NIH HHS
ID : T32 HL144472
Pays : United States
Informations de copyright
© 2024. The Author(s).
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