RT Journal Article
SR Electronic
T1 Hoxa10 mediates positional memory to govern stem cell function in adult skeletal muscle
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2020.07.16.207654
DO 10.1101/2020.07.16.207654
A1 Kiyoshi Yoshioka
A1 Hiroshi Nagahisa
A1 Fumihito Miura
A1 Hiromitsu Araki
A1 Yasutomi Kamei
A1 Yasuo Kitajima
A1 Daiki Seko
A1 Jumpei Nogami
A1 Yoshifumi Tsuchiya
A1 Narihiro Okazaki
A1 Akihiko Yonekura
A1 Seigo Ohba
A1 Yoshinori Sumita
A1 Ko Chiba
A1 Kosei Ito
A1 Izumi Asahina
A1 Yoshihiro Ogawa
A1 Takashi Ito
A1 Yasuyuki Ohkawa
A1 Yusuke Ono
YR 2020
UL http://biorxiv.org/content/early/2020/07/17/2020.07.16.207654.abstract
AB Skeletal muscle stem cells (satellite cells) are distributed throughout the body with heterogeneous properties that corresponds to region-specific pathophysiology. However, topographical genes that have functions remain unidentified in satellite cells of adult muscle. Here, we showed that expression of Homeobox (Hox)-A cluster genes, key regulators of the embryonic body plan, was robustly maintained in both muscles and satellite cells in adult mice and humans, which recapitulates their embryonic origin. We observed that regionally specific expressed Hox genes were linked to hypermethylation of the Hox-A locus. We examined Hoxa10 inactivation in satellite cells and found it led to genomic instability and mitotic catastrophe, which resulted in a decline in the regionally specific regenerative ability of muscles in adult mice. Thus, our results showed that Hox gene expression profiles instill the embryonic history in satellite cells as positional memory, potentially modulating the region-specificity in adult skeletal muscles.Competing Interest StatementThe authors have declared no competing interest.