Notch signaling activation in human embryonic stem cells is required for embryonic, but not trophoblastic, lineage commitment

人类胚胎干细胞中的 Notch 信号激活是胚胎(而非滋养层)谱系承诺所必需的

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作者:Xiaobing Yu, Jizhong Zou, Zhaohui Ye, Holly Hammond, Guibin Chen, Akinori Tokunaga, Prashant Mali, Yue-Ming Li, Curt Civin, Nicholas Gaiano, Linzhao Cheng

Abstract

The Notch signaling pathway plays important roles in cell-fate determination during embryonic development and adult life. In this study, we focus on the role of Notch signaling in governing cell-fate choices in human embryonic stem cells (hESCs). Using genetic and pharmacological approaches, we achieved both blockade and conditional activation of Notch signaling in several hESC lines. We report here that activation of Notch signaling is required for undifferentiated hESCs to form the progeny of all three embryonic germ layers, but not trophoblast cells. In addition, transient Notch signaling pathway activation enhanced generation of hematopoietic cells from committed hESCs. These new insights into the roles of Notch in hESC-fate determination may help to efficiently direct hESC differentiation into therapeutically relevant cell types.

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