title: Notch inhibition promotes human embryonic stem cell-derived cardiac mesoderm differentiation.
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.
authors.affiliation: Department of Obstetrics and Gynecology, Institute of Reproductive Medicine and Population, Medical Research Center, Seoul National University College of Medicine, Chongno-ku, Seoul, Korea. ymchoi@snu.ac.kr
authors.forename: Jiho
authors.initials: J
authors.lastname: Jang
authors.forename: Seung Yup
authors.initials: SY
authors.lastname: Ku
authors.forename: Jung Eun
authors.initials: JE
authors.lastname: Kim
authors.forename: Kyunghee
authors.initials: K
authors.lastname: Choi
authors.forename: Yoon Young
authors.initials: YY
authors.lastname: Kim
authors.forename: Hee Sun
authors.initials: HS
authors.lastname: Kim
authors.forename: Sun Kyung
authors.initials: SK
authors.lastname: Oh
authors.forename: Eun Ju
authors.initials: EJ
authors.lastname: Lee
authors.forename: Hyun-Jai
authors.initials: HJ
authors.lastname: Cho
authors.forename: Young Hwan
authors.initials: YH
authors.lastname: Song
authors.forename: Sang Hun
authors.initials: SH
authors.lastname: Lee
authors.forename: Suk Ho
authors.initials: SH
authors.lastname: Lee
authors.forename: Chang Suk
authors.initials: CS
authors.lastname: Suh
authors.forename: Seok Hyun
authors.initials: SH
authors.lastname: Kim
authors.forename: Shin Yong
authors.initials: SY
authors.lastname: Moon
authors.forename: Young Min
authors.initials: YM
authors.lastname: Choi