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Human muscle-derived CLEC14A-positive cells regenerate muscle independent of PAX7.
- Source :
-
Nature communications [Nat Commun] 2019 Dec 18; Vol. 10 (1), pp. 5776. Date of Electronic Publication: 2019 Dec 18. - Publication Year :
- 2019
-
Abstract
- 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.
- Subjects :
- Animals
Biopsy
Child, Preschool
Consanguinity
Female
Human Umbilical Vein Endothelial Cells
Humans
Male
Mice
Muscle, Skeletal cytology
Muscle, Skeletal injuries
Mutation
PAX7 Transcription Factor metabolism
Primary Cell Culture
Satellite Cells, Skeletal Muscle transplantation
Single-Cell Analysis
Transplantation, Heterologous methods
Wasting Syndrome therapy
Exome Sequencing
Cell Adhesion Molecules physiology
Lectins, C-Type physiology
Muscle, Skeletal physiology
PAX7 Transcription Factor genetics
Regeneration
Satellite Cells, Skeletal Muscle physiology
Wasting Syndrome genetics
Subjects
Details
- Language :
- English
- ISSN :
- 2041-1723
- Volume :
- 10
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Nature communications
- Publication Type :
- Academic Journal
- Accession number :
- 31852888
- Full Text :
- https://doi.org/10.1038/s41467-019-13650-z