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Transcriptome and epigenome diversity and plasticity of muscle stem cells following transplantation


Autoři: Brendan Evano aff001;  Diljeet Gill aff003;  Irene Hernando-Herraez aff003;  Glenda Comai aff001;  Thomas M. Stubbs aff003;  Pierre-Henri Commere aff004;  Wolf Reik aff003;  Shahragim Tajbakhsh aff001
Působiště autorů: Stem Cells & Development, Department of Developmental & Stem Cell Biology, Institut Pasteur, 25 rue du Dr. Roux, Paris, France aff001;  CNRS UMR 3738, Institut Pasteur, Paris, France aff002;  Epigenetics Programme, Babraham Institute, Cambridge, United Kingdom aff003;  Cytometry and Biomarkers, Center for Technological Resources and Research, Institut Pasteur, 28 rue du Dr. Roux, Paris, France aff004
Vyšlo v časopise: Transcriptome and epigenome diversity and plasticity of muscle stem cells following transplantation. PLoS Genet 16(10): e32767. doi:10.1371/journal.pgen.1009022
Kategorie: Research Article
doi: https://doi.org/10.1371/journal.pgen.1009022

Souhrn

Adult skeletal muscles are maintained during homeostasis and regenerated upon injury by muscle stem cells (MuSCs). A heterogeneity in self-renewal, differentiation and regeneration properties has been reported for MuSCs based on their anatomical location. Although MuSCs derived from extraocular muscles (EOM) have a higher regenerative capacity than those derived from limb muscles, the molecular determinants that govern these differences remain undefined. Here we show that EOM and limb MuSCs have distinct DNA methylation signatures associated with enhancers of location-specific genes, and that the EOM transcriptome is reprogrammed following transplantation into a limb muscle environment. Notably, EOM MuSCs expressed host-site specific positional Hox codes after engraftment and self-renewal within the host muscle. However, about 10% of EOM-specific genes showed engraftment-resistant expression, pointing to cell-intrinsic molecular determinants of the higher engraftment potential of EOM MuSCs. Our results underscore the molecular diversity of distinct MuSC populations and molecularly define their plasticity in response to microenvironmental cues. These findings provide insights into strategies designed to improve the functional capacity of MuSCs in the context of regenerative medicine.

Klíčová slova:

Body limbs – DNA methylation – Gene expression – Muscle biochemistry – Muscle differentiation – Muscle regeneration – principal component analysis – Transcriptome analysis


Zdroje

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