G-CSF Promotes the Proliferation of Developing Cardiomyocytes In Vivo and in Derivation from ESCs and iPSCs

Kenichiro Shimoji; Shinsuke Yuasa; Takeshi Onizuka; Fumiyuki Hattori; Tomofumi Tanaka; Mie Hara; Yohei Ohno; Hao Chen; Toru Egasgira; Tomohisa Seki; Kojiro Yae; Uichi Koshimizu; Satoshi Ogawa; Keiichi Fukuda

doi:10.1016/j.stem.2010.01.002

G-CSF Promotes the Proliferation of Developing Cardiomyocytes In Vivo and in Derivation from ESCs and iPSCs

Kenichiro Shimoji, Shinsuke Yuasa, Takeshi Onizuka, Fumiyuki Hattori, Tomofumi Tanaka, Mie Hara, Yohei Ohno, Hao Chen, Toru Egasgira, Tomohisa Seki, Kojiro Yae, Uichi Koshimizu, Satoshi Ogawa, Keiichi Fukuda

Medicine - Cardiology Division

Research output: Contribution to journal › Article › peer-review

102 Scopus citations

Abstract

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.

Original language	English (US)
Pages (from-to)	227-237
Number of pages	11
Journal	Cell Stem Cell
Volume	6
Issue number	3
DOIs	https://doi.org/10.1016/j.stem.2010.01.002
State	Published - Mar 5 2010

Bibliographical note

Funding Information:
This study was supported in part by research grants from the Ministry of Education, Science and Culture, Japan, and by the Program for Promotion of Fundamental Studies in Health Science of the National Institute of Biomedical Innovation, Japan.

Keywords

STEMCELL

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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title = "G-CSF Promotes the Proliferation of Developing Cardiomyocytes In Vivo and in Derivation from ESCs and iPSCs",

abstract = "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.",

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G-CSF Promotes the Proliferation of Developing Cardiomyocytes In Vivo and in Derivation from ESCs and iPSCs

Abstract

Bibliographical note

Keywords

UN SDGs

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