Notch Inhibition Promotes Human Embryonic Stem Cell-Derived Cardiac Mesoderm Differentiation

被引：38

作者：

Jang, Jiho ^{[2
]}

Ku, Seung Yup ^{[1
,2
]}

Kim, Jung Eun ^{[2
]}

Choi, Kyunghee ^{[5
]}

Kim, Yoon Young ^{[2
]}

Kim, Hee Sun ^{[1
,2
]}

Oh, Sun Kyung ^{[1
,2
]}

Lee, Eun Ju ^{[6
]}

Cho, Hyun-Jai ^{[3
]}

Song, Young Hwan ^{[7
]}

Lee, Sang Hun ^{[4
]}

Lee, Suk Ho ^{[4
]}

Suh, Chang Suk ^{[1
,2
]}

Kim, Seok Hyun ^{[1
,2
]}

Moon, Shin Yong ^{[1
,2
]}

Choi, Young Min ^{[1
,2
]}

机构：

[1] Seoul Natl Univ, Coll Med, Dept Obstet & Gynecol, Seoul 110810, South Korea

[2] Seoul Natl Univ, Coll Med, Inst Reprod Med & Populat, Med Res Ctr, Seoul 110810, South Korea

[3] Seoul Natl Univ, Coll Med, Dept Internal Med, Seoul 110810, South Korea

[4] Seoul Natl Univ, Coll Med, Dept Physiol, Seoul 110810, South Korea

[5] Washington Univ, Sch Med, Dept Pathol & Immunol, St Louis, MO USA

[6] Seoul Natl Univ Hosp, Clin Res Inst, Seoul 110744, South Korea

[7] Inje Univ, Coll Med, Sanggye Paik Hosp, Dept Pediat, Seoul, South Korea

来源：

STEM CELLS | 2008年 / 26卷 / 11期

关键词：

Human embryonic stem cell; Notch; gamma-Secretase inhibitor; Cardiac mesoderm;

D O I：

10.1634/stemcells.2007-1053

中图分类号：

Q813 [细胞工程];

学科分类号：

摘要：

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. STEM CELLS 2008;26:2782-2790

引用

页码：2782 / 2790

页数：9

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