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

• Published in: PLoS genetics Vol. 16; no. 10; p. e1009022
• Main Authors: Evano, Brendan, Gill, Diljeet, Hernando-Herraez, Irene, Comai, Glenda, Stubbs, Thomas M, Commere, Pierre-Henri, Reik, Wolf, Tajbakhsh, Shahragim
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 30.10.2020; Public Library of Science (PLoS)
• Subjects: Animals; Biology; Biology and life sciences; Cell differentiation; Cell Differentiation - genetics; Cell Lineage - genetics; Cell Plasticity - genetics; Cell Proliferation - genetics; Cell self-renewal; Deoxyribonucleic acid; DNA; DNA methylation; Engraftment; Enhancers; Epigenetics; Epigenome - genetics; Extremities - growth & development; Gene expression; Genetic aspects; Genetic Variation - genetics; Homeostasis; Humans; Investigations; Life Sciences; Medicine and Health Sciences; Mice; Mice, Inbred C57BL; Muscle Cells - cytology; Muscle Fibers, Skeletal; Muscle, Skeletal - cytology; Muscles; Myoblasts - cytology; Oculomotor system; Physical Sciences; Physiological aspects; Principal components analysis; Regeneration - genetics; Regenerative medicine; Research and Analysis Methods; Skeletal muscle; Software; Stem Cell Transplantation; Stem cells; Stem Cells - cytology; Stem Cells - metabolism; Transcription factors; Transcriptome - genetics; Transplantation; United Kingdom; United Kingdom > UK; France
• ISSN: 1553-7404; 1553-7390; 1553-7404
• DOI: 10.1371/journal.pgen.1009022

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.