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Postnatal memory governs cell function in adult skeletal muscle.

ABSTRACT: Skeletal muscle is the contractile tissue that distributes throughout body, with its functionally heterogeneous properties amongst muscles, which may relate to region specific pathology of muscle diseases. Here we found that homeobox (Hox) genes, key regulators of body-plan in the embryo, are region-specifically and robustly maintained as positional memory in both muscle and its associated stem cells named satellite cells in adult mice and humans. Although satellite cell function in adults was unaffected by genetic loss of Hoxa10 in muscle progenitors at the developmental stage, postnatal deletion of Hoxa10 in satellite cells led to genomic instability and mitosis abnormality, resulting in a remarkable decline in regenerative ability of muscles in a region-specific manner. Our results suggest that Hox-based positional memory is flexibly established during embryonic development and governs topographic function of stem cells in adult muscles once it is fixed, potentially influencing the region-specific weakness in muscle diseases

ORGANISM(S): Mus musculus

PROVIDER: GSE139639 | GEO | 2021/07/08

REPOSITORIES: GEO

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

Project description: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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Hoxa10 is a functional positional memory that governs stem cell function in adult skeletal muscle

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

Project description:Hoxa10 mediates positional memory to govern stem cell function in adult skeletal muscle

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Hoxa10 is a functional positional memory that governs stem cell function in adult skeletal muscle

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Transcription profiling of human fibroblasts to examine diversity, topographic differentiation and positional memory

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