Publications
Detailed Information
Notch inhibition promotes human embryonic stem cell-derived cardiac mesoderm differentiation
Cited 35 time in
Web of Science
Cited 41 time in Scopus
- Authors
- Issue Date
- 2008-09-02
- Publisher
- Wiley-Blackwell
- Citation
- Stem Cells. 2008;26(11):2782-2790
- Keywords
- Amyloid Precursor Protein Secretases/antagonists & inhibitors ; Animals ; Animals, Newborn ; Cell Differentiation ; Cells, Cultured ; Coculture Techniques ; Embryonic Stem Cells/*cytology ; Humans ; Mesoderm/*cytology/metabolism ; Myocardium/*cytology ; Myocytes, Cardiac/*metabolism ; Oligopeptides/*pharmacology ; Rats ; Rats, Sprague-Dawley ; Signal 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
https://hdl.handle.net/10371/68133
- Files in This Item:
- There are no files associated with this item.
- Appears in Collections:
Item View & Download Count
Items in S-Space are protected by copyright, with all rights reserved, unless otherwise indicated.