Hoxa10 mediates positional memory to govern stem cell function in adult skeletal muscle
| Autor: | Yasuyuki Ohkawa, Daiki Seko, Fumihito Miura, Yoshihiro Ogawa, Yoshifumi Tsuchiya, Yasutomi Kamei, Kosei Ito, Akihiko Yonekura, Narihiro Okazaki, Jumpei Nogami, Hiromitsu Araki, Kiyoshi Yoshioka, Hiroshi Nagahisa, Ko Chiba, Izumi Asahina, Yusuke Ono, Yasuo Kitajima, Yoshinori Sumita, Takashi Ito, Seigo Ohba |
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| Rok vydání: | 2021 |
| Předmět: |
Mesoderm
Biology Myoblasts Mice 03 medical and health sciences 0302 clinical medicine mental disorders medicine Animals Muscle Skeletal Hox gene Gene Mitotic catastrophe Research Articles 030304 developmental biology 0303 health sciences Multidisciplinary Stem Cells Genes Homeobox SciAdv r-articles Life Sciences Skeletal muscle biology.organism_classification Embryonic stem cell Cell biology Homeobox A10 Proteins medicine.anatomical_structure DNA methylation Homeobox Satellite (biology) Stem cell 030217 neurology & neurosurgery Research Article Developmental Biology |
| Zdroj: | Science Advances |
| ISSN: | 2375-2548 |
| Popis: | Adult muscles and their associated stem cells retain functional positional memory based on developmental origin. 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. |
| Databáze: | OpenAIRE |
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