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

Jiho Jang, Yup Ku Seung, Eun Kim Jung, Kyunghee Choi, Young Kim Yoon, Sun Kim Hee, Kyung Oh Sun, Ju Lee Eun, Hyun Jai Cho, Hwan Song Young, Hun Lee Sang, Ho Lee Suk, Suk Suh Chang, Hyun Kim Seok, Yong Moon Shin, Min Choi Young

Research output: Contribution to journalArticlepeer-review

42 Scopus citations

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 γ-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.

Original languageEnglish
Pages (from-to)2782-2790
Number of pages9
JournalSTEM CELLS
Volume26
Issue number11
DOIs
StatePublished - Nov 2008

Keywords

  • Cardiac mesoderm
  • Human embryonic stem cell
  • Notch
  • γ-secretase inhibitor

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