Helmholtz Gemeinschaft

Search
Browse
Statistics
Feeds

Human muscle-derived CLEC14A-positive cells regenerate muscle independent of PAX7

[thumbnail of Original Article]
Preview
PDF (Original Article) - Requires a PDF viewer such as GSview, Xpdf or Adobe Acrobat Reader
3MB
[thumbnail of Supplementary Information] Other (Supplementary Information)
60MB

Item Type:Article
Title:Human muscle-derived CLEC14A-positive cells regenerate muscle independent of PAX7
Creators Name:Marg, A., Escobar Fernandez, H., Karaiskos, N., Grunwald, S.A., Metzler, E., Kieshauer, J., Sauer, S., Pasemann, D., Malfatti, E., Mompoint, D., Quijano-Roy, S., Boltengagen, A., Schneider, J., Schülke, M., Kunz, S., Carlier, R., Birchmeier, C., Amthor, H., Spuler, A., Kocks, C., Rajewsky, N. and Spuler, S.
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.
Keywords:Biopsy, C-Type Lectins, Cell Adhesion Molecules, Consanguinity, Heterologous Transplantation, Human Umbilical Vein Endothelial Cells, Mutation, PAX7 Transcription Factor, Primary Cell Culture, Regeneration, Single-Cell Analysis, Skeletal Muscle, Skeletal Muscle Satellite Cells, Wasting Syndrome, Whole Exome Sequencing, Animals, Mice
Source:Nature Communications
ISSN:2041-1723
Publisher:Nature Publishing Group
Volume:10
Number:1
Page Range:5776
Date:18 December 2019
Official Publication:https://doi.org/10.1038/s41467-019-13650-z
PubMed:View item in PubMed

Repository Staff Only: item control page

Downloads

Downloads per month over past year

Open Access
MDC Library