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Notch inhibition promotes human embryonic stem cell-derived cardiac mesoderm differentiation

Cited 33 time in Web of Science Cited 36 time in Scopus
Authors
Jang, Jiho; Ku, Seung Yup; Kim, Jung Eun; Choi, Kyunghee; Kim, Yoon Young; Kim, Hee Sun; Oh, Sun Kyung; Lee, Eun Ju; Cho, Hyun-Jai; Song, Young Hwan; Lee, Sang Hun; Lee, Suk Ho; Suh, Chang Suk; Kim, Seok Hyun; Moon, Shin Yong; Choi, Young Min
Issue Date
2008-09-02
Publisher
Wiley-Blackwell
Citation
Stem Cells. 2008;26(11):2782-2790
Keywords
Amyloid Precursor Protein Secretases/antagonists & inhibitorsAnimalsAnimals, NewbornCell DifferentiationCells, CulturedCoculture TechniquesEmbryonic Stem Cells/*cytologyHumansMesoderm/*cytology/metabolismMyocardium/*cytologyMyocytes, Cardiac/*metabolismOligopeptides/*pharmacologyRatsRats, Sprague-DawleySignal Transduction
Abstract
The roles of Notch signaling in cardiac differentiation from murine embryonic stem cells have been well documented. We investigated whether Notch signaling plays a similar role in human embryonic stem cells (hESCs). Although, as previously reported, blocking Notch signaling via the addition of gamma-secretase inhibitor (GSI) alone failed to affect hESC differentiation, we found that GSI plus reduced-volume culture medium (GSI/RVCM) accelerated mesodermal differentiation. GSI/RVCM conditions simultaneously suppressed commitment toward neuroectodermal lineages. Furthermore, sustained inhibition of Notch signaling further enhanced differentiation into cardiac mesoderm. Spontaneous beating activity was typically observed from 12 days after initiation of GSI treatment in RVCM. Moreover, hESC-derived cardiomyocytes expressed connexin 43 and possessed spontaneous calcium oscillations and cardiomyocyte beats coupled to neonatal rat cardiomyocytes when cocultured. These findings strongly suggest a distinct role for Notch signaling in the induction and specification of hESC-derived cardiac mesoderm in vitro. Disclosure of potential conflicts of interest is found at the end of this article.
ISSN
1549-4918 (Electronic)
Language
English
URI
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=18757302

http://hdl.handle.net/10371/68133
DOI
https://doi.org/10.1634/stemcells.2007-1053
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College of Medicine/School of Medicine (의과대학/대학원)Dept. of Physiology (생리학교실)Journal Papers (저널논문_생리학교실)
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