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Publication : Hoxa10 mediates positional memory to govern stem cell function in adult skeletal muscle.

First Author  Yoshioka K Year  2021
Journal  Sci Adv Volume  7
Issue  24 PubMed ID  34108202
Mgi Jnum  J:314242 Mgi Id  MGI:6813953
Doi  10.1126/sciadv.abd7924 Citation  Yoshioka K, et al. (2021) Hoxa10 mediates positional memory to govern stem cell function in adult skeletal muscle. Sci Adv 7(24)
abstractText  Muscle stem cells (satellite cells) are distributed throughout the body and have heterogeneous properties among muscles. However, functional topographical genes in satellite cells of adult muscle remain unidentified. Here, we show that expression of Homeobox-A (Hox-A) cluster genes accompanied with DNA hypermethylation of the Hox-A locus was robustly maintained in both somite-derived muscles and their associated satellite cells in adult mice, which recapitulates their embryonic origin. Somite-derived satellite cells were clearly separated from cells derived from cranial mesoderm in Hoxa10 expression. Hoxa10 inactivation led to genomic instability and mitotic catastrophe in somite-derived satellite cells in mice and human. Satellite cell-specific Hoxa10 ablation in mice resulted in a decline in the regenerative ability of somite-derived muscles, which were unobserved in cranial mesoderm-derived muscles. Thus, our results show that Hox gene expression profiles instill the embryonic history in satellite cells as positional memory, potentially modulating region-specific pathophysiology in adult muscles.
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