Noggle Scott A, Weiler Deborah, Condie Brian G
Department of Genetics, University of Georgia, Davison Life Sciences Complex, Athens, 30602, USA.
Stem Cells. 2006 Jul;24(7):1646-53. doi: 10.1634/stemcells.2005-0314. Epub 2006 Apr 13.
The NOTCH signaling pathway performs a wide range of critical functions in a number of different cell types during development and differentiation. The role of NOTCH signals in human embryonic stem cells (hESCs) has not been tested. We measured the activity of canonical NOTCH signaling in undifferentiated embryonic stem (ES) cells and tested the requirement for NOTCH activity in hESC self-renewal or differentiation by growing hESCs in the presence of gamma-secretase inhibitors. Our results suggest that NOTCH signaling is not required for the propagation of undifferentiated human ES cells but instead is required for the maintenance of the differentiating cell types that accumulate in human ES cell cultures. Our studies suggest that NOTCH signaling is not required in human embryonic differentiation until the formation of extraembryonic, germ layer, or tissue-specific stem cells and progenitors.
NOTCH信号通路在发育和分化过程中的多种不同细胞类型中发挥着广泛的关键功能。NOTCH信号在人类胚胎干细胞（hESC）中的作用尚未得到检验。我们测量了未分化胚胎干细胞（ES细胞）中经典NOTCH信号的活性，并通过在γ-分泌酶抑制剂存在的情况下培养hESC，测试了hESC自我更新或分化过程中对NOTCH活性的需求。我们的结果表明，未分化的人类ES细胞的增殖不需要NOTCH信号，而是人类ES细胞培养物中积累的分化细胞类型的维持需要NOTCH信号。我们的研究表明，在人类胚胎分化过程中，直到形成胚外、胚层或组织特异性干细胞和祖细胞之前，NOTCH信号都是不需要的。
