Human muscle-derived CLEC14A-positive cells regenerate muscle independent of PAX7.
Animals
Biopsy
Cell Adhesion Molecules
/ physiology
Child, Preschool
Consanguinity
Female
Human Umbilical Vein Endothelial Cells
Humans
Lectins, C-Type
/ physiology
Male
Mice
Muscle, Skeletal
/ cytology
Mutation
PAX7 Transcription Factor
/ genetics
Primary Cell Culture
Regeneration
Satellite Cells, Skeletal Muscle
/ physiology
Single-Cell Analysis
Transplantation, Heterologous
/ methods
Wasting Syndrome
/ genetics
Exome Sequencing
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
18 12 2019
18 12 2019
Historique:
received:
06
05
2019
accepted:
11
11
2019
entrez:
20
12
2019
pubmed:
20
12
2019
medline:
3
4
2020
Statut:
epublish
Résumé
Skeletal muscle stem cells, called satellite cells and defined by the transcription factor PAX7, are responsible for postnatal muscle growth, homeostasis and regeneration. Attempts to utilize the regenerative potential of muscle stem cells for therapeutic purposes so far failed. We previously established the existence of human PAX7-positive cell colonies with high regenerative potential. We now identified PAX7-negative human muscle-derived cell colonies also positive for the myogenic markers desmin and MYF5. These include cells from a patient with a homozygous PAX7 c.86-1G > A mutation (PAX7null). Single cell and bulk transcriptome analysis show high intra- and inter-donor heterogeneity and reveal the endothelial cell marker CLEC14A to be highly expressed in PAX7null cells. All PAX7-negative cell populations, including PAX7null, form myofibers after transplantation into mice, and regenerate muscle after reinjury. Transplanted PAX7neg cells repopulate the satellite cell niche where they re-express PAX7, or, strikingly, CLEC14A. In conclusion, transplanted human cells do not depend on PAX7 for muscle regeneration.
Identifiants
pubmed: 31852888
doi: 10.1038/s41467-019-13650-z
pii: 10.1038/s41467-019-13650-z
pmc: PMC6920394
doi:
Substances chimiques
CLEC14A protein, human
0
Cell Adhesion Molecules
0
Lectins, C-Type
0
PAX7 Transcription Factor
0
PAX7 protein, human
0
Types de publication
Case Reports
Journal Article
Research Support, Non-U.S. Gov't
Video-Audio Media
Langues
eng
Sous-ensembles de citation
IM
Pagination
5776Références
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