TY - JOUR
T1 - Calcitonin Receptor Signaling Inhibits Muscle Stem Cells from Escaping the Quiescent State and the Niche
AU - Yamaguchi, Masahiko
AU - Watanabe, Yoko
AU - Ohtani, Takuji
AU - Uezumi, Akiyoshi
AU - Mikami, Norihisa
AU - Nakamura, Miki
AU - Sato, Takahiko
AU - Ikawa, Masahito
AU - Hoshino, Mikio
AU - Tsuchida, Kunihiro
AU - Miyagoe-Suzuki, Yuko
AU - Tsujikawa, Kazutake
AU - Takeda, Shin'ichi
AU - Yamamoto, Hiroshi
AU - Fukada, So ichiro
N1 - Funding Information:
We thank Yoko Esaki and Kiyo Kawata of NPO Biotechnology Research and Development for technical assistance in generating Calcr flox mice, A.F. Stewart for permitting use of CAG-Flpe transgenic mice, and Prof. Toshio Kitamura for providing the pMXs vector and packaging cells. We also thank Prof. Shahragim Tajbakhsh for technical advice. We appreciate the KOMP project for Calcr targeting vectors. This work was supported by a JSPS KAKENHI grant, a Grant-in Aid for Young Scientists (S.F.), an Intramural Research Grant (S.F.) for Neurological and Psychiatric Disorders of NCNP, and the Takeda Science Foundation (S.F.).
Publisher Copyright:
© 2015 The Authors.
PY - 2015/10/13
Y1 - 2015/10/13
N2 - Calcitonin receptor (Calcr) is expressed in adult muscle stem cells (muscle satellite cells [MuSCs]). To elucidate the role of Calcr, we conditionally depleted Calcr from adult MuSCs and found that impaired regeneration after muscle injury correlated with the decreased number of MuSCs in Calcr-conditional knockout (cKO) mice. Calcr signaling maintained MuSC dormancy via the cAMP-PKA pathway but had no impact on myogenic differentiation of MuSCs in an undifferentiated state. The abnormal quiescent state in Calcr-cKO mice resulted in a reduction of the MuSC pool by apoptosis. Furthermore, MuSCs were found outside their niche in Calcr-cKO mice, demonstrating cell relocation. This emergence from the sublaminar niche was prevented by the Calcr-cAMP-PKA and Calcr-cAMP-Epac pathways downstream of Calcr. Altogether, the findings demonstrated that Calcr exerts its effect specifically by keeping MuSCs in a quiescent state and in their location, maintaining the MuSC pool.
AB - Calcitonin receptor (Calcr) is expressed in adult muscle stem cells (muscle satellite cells [MuSCs]). To elucidate the role of Calcr, we conditionally depleted Calcr from adult MuSCs and found that impaired regeneration after muscle injury correlated with the decreased number of MuSCs in Calcr-conditional knockout (cKO) mice. Calcr signaling maintained MuSC dormancy via the cAMP-PKA pathway but had no impact on myogenic differentiation of MuSCs in an undifferentiated state. The abnormal quiescent state in Calcr-cKO mice resulted in a reduction of the MuSC pool by apoptosis. Furthermore, MuSCs were found outside their niche in Calcr-cKO mice, demonstrating cell relocation. This emergence from the sublaminar niche was prevented by the Calcr-cAMP-PKA and Calcr-cAMP-Epac pathways downstream of Calcr. Altogether, the findings demonstrated that Calcr exerts its effect specifically by keeping MuSCs in a quiescent state and in their location, maintaining the MuSC pool.
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U2 - 10.1016/j.celrep.2015.08.083
DO - 10.1016/j.celrep.2015.08.083
M3 - Article
C2 - 26440893
AN - SCOPUS:84944060460
SN - 2211-1247
VL - 13
SP - 302
EP - 314
JO - Cell Reports
JF - Cell Reports
IS - 2
ER -