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

Research output: Contribution to journalArticle

87 Citations (Scopus)

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 languageEnglish
Pages (from-to)227-237
Number of pages11
JournalCell stem cell
Volume6
Issue number3
DOIs
Publication statusPublished - 2010 Mar 5

Keywords

  • STEMCELL

ASJC Scopus subject areas

  • Molecular Medicine
  • Genetics
  • Cell Biology

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    Shimoji, K., Yuasa, S., Onizuka, T., Hattori, F., Tanaka, T., Hara, M., Ohno, Y., Chen, H., Egasgira, T., Seki, T., Yae, K., Koshimizu, U., Ogawa, S., & Fukuda, K. (2010). G-CSF Promotes the Proliferation of Developing Cardiomyocytes In Vivo and in Derivation from ESCs and iPSCs. Cell stem cell, 6(3), 227-237. https://doi.org/10.1016/j.stem.2010.01.002