G-CSF promotes the proliferation of developing cardiomyocytes in vivo and in derivation from ESCs and iPSCs.
During a screen for humoral factors that promote cardiomyocyte differentiation from embryonic stem cells (ESCs), we found marked elevation of granulocyte colony-stimulating factor receptor (G-CSFR) mRNA in developing cardiomyocytes. We confirmed that both G-CSFR and G-CSF were specifically expressed in embryonic mouse heart at the midgestational stage, and expression levels were maintained throughout embryogenesis. Intrauterine G-CSF administration induced embryonic cardiomyocyte proliferation and caused hyperplasia. In contrast, approximately 50% of csf3r(-/-) mice died during late embryogenesis because of the thinning of atrioventricular walls. ESC-derived developing cardiomyocytes also strongly expressed G-CSFR. When extrinsic G-CSF was administered to the ESC- and human iPSC-derived cardiomyocytes, it markedly augmented their proliferation. Moreover, G-CSF-neutralizing antibody inhibited their proliferation. These findings indicated that G-CSF is critically involved in cardiomyocyte proliferation during development, and may be used to boost the yield of cardiomyocytes from ESCs for their potential application to regenerative medicine.
Shimoji
Kenichiro
K
Department of Regenerative Medicine and Advanced Cardiac Therapeutics, Keio University School of Medicine, Tokyo 160-8582, Japan.
Yuasa
Shinsuke
S
Onizuka
Takeshi
T
Hattori
Fumiyuki
F
Tanaka
Tomofumi
T
Hara
Mie
M
Ohno
Yohei
Y
Chen
Hao
H
Egasgira
Toru
T
Seki
Tomohisa
T
Yae
Kojiro
K
Koshimizu
Uichi
U
Ogawa
Satoshi
S
Fukuda
Keiichi
K
D000818:Animals; D049109:Cell Proliferation; D002478:Cells, Cultured; D053595:Embryonic Stem Cells / Q000166:cytology / Q000378:metabolism*; D016179:Granulocyte Colony-Stimulating Factor / Q000378:metabolism*; D006321:Heart / Q000196:embryology*; D006801:Humans; D057026:Induced Pluripotent Stem Cells / Q000166:cytology / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D032383:Myocytes, Cardiac / Q000166:cytology / Q000378:metabolism*; D016188:Receptors, Granulocyte Colony-Stimulating Factor / Q000172:deficiency / Q000378:metabolism
D016188:Receptors, Granulocyte Colony-Stimulating Factor; D016179:Granulocyte Colony-Stimulating Factor