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

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

doi:10.1016/j.stem.2010.01.002

Cited by 114 publications

(77 citation statements)

References 32 publications

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“…This finding is partially consistent with studies on mouse embryonic stem cells (mESCs) that demonstrate that the administration of Noggin before the initiation of differentiation promotes cardiogenesis [9]. Further comparing Noggin-treated cells with nontreated cells revealed that granulocyte colony-stimulating factor (G-CSF) promotes the proliferation of developing cardiomyocytes derived from mESCs [30]. Noggin sustains the undifferentiated proliferation of hESCs [31], and BMP4 is required for mESC self-renewal [32].…”

Section: Discussionsupporting

confidence: 83%

Direct differentiation of atrial and ventricular myocytes from human embryonic stem cells by alternating retinoid signals

et al. 2010

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Although myocyte cell transplantation studies have suggested a promising therapeutic potential for myocardial infarction, a major obstacle to the development of clinical therapies for myocardial repair is the difficulties associated with obtaining relatively homogeneous ventricular myocytes for transplantation. Human embryonic stem cells (hESCs) are a promising source of cardiomyocytes. Here we report that retinoid signaling regulates the fate specification of atrial versus ventricular myocytes during cardiac differentiation of hESCs. We found that both Noggin and the panretinoic acid receptor antagonist BMS-189453 (RAi) significantly increased the cardiac differentiation efficiency of hESCs. To investigate retinoid functions, we compared Noggin+RAi-treated cultures with Noggin+RA-treated cultures. Our results showed that the expression levels of the ventricular-specific gene IRX-4 were radically elevated in Noggin+RAi-treated cultures. MLC-2V, another ventricular-specific marker, was expressed in the majority of the cardiomyocytes in Noggin+RAi-treated cultures, but not in the cardiomyocytes of Noggin+RA-treated cultures. Flow cytometry analysis and electrophysiological studies indicated that with 64.7 ± 0.88% (mean ± s.e.m) cardiac differentiation efficiency, 83% of the cardiomyocytes in Noggin+RAi-treated cultures had embryonic ventricular-like action potentials (APs). With 50.7 ± 1.76% cardiac differentiation efficiency, 94% of the cardiomyocytes in Noggin+RA-treated cultures had embryonic atrial-like APs. These results were further confirmed by imaging studies that assessed the patterns and properties of the Ca 2+ sparks of the cardiomyocytes from the two cultures. These findings demonstrate that retinoid signaling specifies the atrial versus ventricular differentiation of hESCs. This study also shows that relatively homogeneous embryonic atrial-and ventricular-like myocyte populations can be efficiently derived from hESCs by specifically regulating Noggin and retinoid signals.

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Section: Discussionsupporting

confidence: 83%

Direct differentiation of atrial and ventricular myocytes from human embryonic stem cells by alternating retinoid signals

et al. 2010

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“…Such evidence indicated that asymmetric protein distribution produces asymmetric cell division, which has a critical role in maintaining the SC population. In our previous screen for myocyte differentiationpromoting factors 6,7 , we noted markedly elevated expression of granulocyte colony-stimulating factor receptor (G-CSFR, encoded by csf3r) in the developing somite 8 . Furthermore, G-CSFR was transiently expressed in regenerating myocytes of adult injured skeletal muscle, and extrinsic G-CSF supported short-term muscle regeneration in cardiotoxin-induced skeletal muscle injury 9 and crush injury 10 .…”

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confidence: 99%

G-CSF supports long-term muscle regeneration in mouse models of muscular dystrophy

et al. 2015

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“…Recent studies have shown that both BMP-2 and FGF-2 play an important role in early heart development, especially in the induction of the mesoderm component at the time of the formation of the three embryonic germ layers (Shimoji et al, 2010;Yuasa et al, 2005). In the present experimental protocol, this stage may correspond to the first three days of embryoid body formation.…”

Section: Long-term Cultivation Of Mipscs In Serum-free Medium 721mentioning

confidence: 93%

“…In the present experimental protocol, this stage may correspond to the first three days of embryoid body formation. Other studies have reported cardiomyocyte differentiation in spheroid cultures with fetal bovine serum or various inhibitors and hormones (Shimoji et al, 2010;Yuasa et al, 2005;Fujiwara et al, 2011;Hao et al, 2008;Olson et al, 2003;Pandur et al, 2002). This is a novel protocol to successfully elicit in vitro cardiomyogenic differentiation of miPS cells under defined serum-free culture conditions using FGF-2 and BMP-2.…”

Section: Long-term Cultivation Of Mipscs In Serum-free Medium 721mentioning

confidence: 99%

Long-term serial cultivation of mouse induced pluripotent stem cells in serum-free and feeder-free defined medium

Yamasaki¹,

Nabeshima²,

Sotomaru³

et al. 2013

Int. J. Dev. Biol.

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Mouse embryonic stem (mES) cells and mouse induced pluripotent stem (miPS) cells are commonly maintained on inactivated mouse embryonic fibroblast feeder cells in medium supplemented with fetal bovine serum or proprietary replacements. An undefined medium containing unknown quantities of reagents has limited the development of applications for pluripotent cells because of the relative lack of knowledge regarding cell responses to differentiating growth factors. Therefore we developed a serum-free medium, designated ESF7, in which mES cells can be maintained in an undifferentiated state without feeder cells. The medium was tested for culturing miPS cells. The miPS cells have been maintained in ESF7 medium for more than 3 years with an undifferentiated phenotype manifested by the expression of pluripotency marker genes and alkaline phosphatase, and these cells exhibited largely normal karyotypes. Furthermore, we found that fibroblast growth factor-2 (FGF-2) with heparin induced miPS cell differentiation into neuronal cells, both in an adherent monolayer and in embryoid body suspension culture. Moreover, we found that FGF-2 with bone morphogenetic protein 2 induced miPS cell differentiation into cardiomyocytes in embryoid body suspension culture. Furthermore, we transplanted subcutaneously miPS cells maintained in ESF7 into the dorsal flanks of SCID mice; all of the transplants produced tumors with tissues derived from all three embryonic germ layers. As this simple serum-free adherent monoculture system supports the long-term propagation of pluripotent iPS cells in vitro, it will allow us to elucidate cell responses to growth factors under defined conditions, and it should provide useful information for differentiation protocols for human iPS cells.

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

Cited by 114 publications

References 32 publications

Direct differentiation of atrial and ventricular myocytes from human embryonic stem cells by alternating retinoid signals

Direct differentiation of atrial and ventricular myocytes from human embryonic stem cells by alternating retinoid signals

G-CSF supports long-term muscle regeneration in mouse models of muscular dystrophy

Long-term serial cultivation of mouse induced pluripotent stem cells in serum-free and feeder-free defined medium

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