TY - JOUR
T1 - Uhrf1 governs the proliferation and differentiation of muscle satellite cells
AU - Sakai, Hiroshi
AU - Sawada, Yuichiro
AU - Tokunaga, Naohito
AU - Tanaka, Kaori
AU - Nakagawa, So
AU - Sakakibara, Iori
AU - Ono, Yusuke
AU - Fukada, So ichiro
AU - Ohkawa, Yasuyuki
AU - Kikugawa, Tadahiko
AU - Saika, Takashi
AU - Imai, Yuuki
N1 - Funding Information:
We thank S. Tajbakhsh for critically reading the manuscript, S. Nakanishi and A. Nishio for their technical support, K. Kameda for the flow cytometry support, and other members of the Division of Analytical Bio-Medicine and the Division of Laboratory Animal Research, the Advanced Research Support Center, Ehime University. This work was supported in part by MEXT/JSPS KAKENHI (JP18H06439 and JP19K19947 to H.S.; JP23689066, JP15H04961, JP15K15552, JP17K19728, JP19H03786 to Y.I.); HIRAKU-Global Program, which is funded by MEXT's “Strategic Professional Development Program for Young Researchers” (to H.S.); and The Nakatomi Foundation and Takeda Science Foundation (to H.S. and Y.I.), UCBJ (to Y.I.) and by the Joint Usage/Research Center for Developmental Medicine, IMEG, Kumamoto University. This work was partly performed in the Cooperative Research Project Program of the Medical Institute of Bioregulation, Kyushu University. Conceptualization, H.S. and Y.I.; Methodology, H.S. K.T. S.N. I.S. Y.O. S.F. and Y.O.; Software, H.S. N.T. K.T. and S.N.; Validation, H.S. and Y.S.; Formal analysis, H.S. N.T. K.T. and S.N.; Investigation, H.S. Y.S. and N.T.; Resources, Y.O. S.F. and Y.O.; Data curation, H.S. N.T. and K.T.; Writing—original draft, H.S. and Y.I.; Writing—review & editing, H.S. and Y.I.; Visualization, H.S. and Y.S.; Supervision, H.S. T.K. T.S. and Y.I.; Project administration, Y.I.; Funding acquisition, H.S. T.K. T.S. and Y.I. The authors declare no competing interests.
Funding Information:
We thank S. Tajbakhsh for critically reading the manuscript, S. Nakanishi and A. Nishio for their technical support, K. Kameda for the flow cytometry support, and other members of the Division of Analytical Bio-Medicine and the Division of Laboratory Animal Research, the Advanced Research Support Center, Ehime University . This work was supported in part by MEXT / JSPS KAKENHI ( JP18H06439 and JP19K19947 to H.S.; JP23689066 , JP15H04961 , JP15K15552 , JP17K19728 , JP19H03786 to Y.I.); HIRAKU-Global Program, which is funded by MEXT 's “Strategic Professional Development Program for Young Researchers” (to H.S.); and The Nakatomi Foundation and Takeda Science Foundation (to H.S. and Y.I.), UCBJ (to Y.I.) and by the Joint Usage/ Research Center for Developmental Medicine , IMEG , Kumamoto University . This work was partly performed in the Cooperative Research Project Program of the Medical Institute of Bioregulation, Kyushu University.
Publisher Copyright:
© 2022 The Author(s)
PY - 2022/3/18
Y1 - 2022/3/18
N2 - DNA methylation is an essential form of epigenetic regulation responsible for cellular identity. In muscle stem cells, termed satellite cells, DNA methylation patterns are tightly regulated during differentiation. However, it is unclear how these DNA methylation patterns affect the function of satellite cells. We demonstrate that a key epigenetic regulator, ubiquitin like with PHD and RING finger domains 1 (Uhrf1), is activated in proliferating myogenic cells but not expressed in quiescent satellite cells or differentiated myogenic cells in mice. Ablation of Uhrf1 in mouse satellite cells impairs their proliferation and differentiation, leading to failed muscle regeneration. Uhrf1-deficient myogenic cells exhibited aberrant upregulation of transcripts, including Sox9, with the reduction of DNA methylation level of their promoter and enhancer region. These findings show that Uhrf1 is a critical epigenetic regulator of proliferation and differentiation in satellite cells, by controlling cell-type-specific gene expression via maintenance of DNA methylation.
AB - DNA methylation is an essential form of epigenetic regulation responsible for cellular identity. In muscle stem cells, termed satellite cells, DNA methylation patterns are tightly regulated during differentiation. However, it is unclear how these DNA methylation patterns affect the function of satellite cells. We demonstrate that a key epigenetic regulator, ubiquitin like with PHD and RING finger domains 1 (Uhrf1), is activated in proliferating myogenic cells but not expressed in quiescent satellite cells or differentiated myogenic cells in mice. Ablation of Uhrf1 in mouse satellite cells impairs their proliferation and differentiation, leading to failed muscle regeneration. Uhrf1-deficient myogenic cells exhibited aberrant upregulation of transcripts, including Sox9, with the reduction of DNA methylation level of their promoter and enhancer region. These findings show that Uhrf1 is a critical epigenetic regulator of proliferation and differentiation in satellite cells, by controlling cell-type-specific gene expression via maintenance of DNA methylation.
UR - http://www.scopus.com/inward/record.url?scp=85125284377&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85125284377&partnerID=8YFLogxK
U2 - 10.1016/j.isci.2022.103928
DO - 10.1016/j.isci.2022.103928
M3 - Article
AN - SCOPUS:85125284377
VL - 25
JO - iScience
JF - iScience
SN - 2589-0042
IS - 3
M1 - 103928
ER -