Hubrecht Institute for Developmental Biology and Stem Cell Research and University Medical Centre Utrecht, Uppsalalaan 8, Utrecht 3584CT, Netherlands.
Nat Commun. 2010 May 17;1(2):18. doi: 10.1038/ncomms1017.
Intestinal cells are constantly produced from a stem cell reservoir that gives rise to proliferating transient amplifying cells, which subsequently differentiate into one of the four principal cell types. Signalling pathways, including the Notch signalling pathway, coordinate these differentiation processes and their deregulation may cause cancer. Pharmacological inhibition through γ-secretase inhibitors or genetic inactivation of the Notch signalling pathway results in the complete loss of proliferating crypt progenitors due to their conversion into post-mitotic goblet cells. The basic helix-loop-helix transcription factor Math1 is essential for intestinal secretory cell differentiation. Because of the critical roles of both Math1 and Notch signalling in intestinal homeostasis and neoplastic transformation, we sought to determine the genetic hierarchy regulating the differentiation of intestinal stem cells into secretory cells. In this paper, we demonstrate that the conversion of intestinal stem cells into goblet cells upon inhibition of the Notch signalling pathway requires Math1.
肠细胞不断从干细胞库中产生，这些干细胞会产生增殖的短暂扩增细胞，这些细胞随后分化为四种主要细胞类型之一。信号通路，包括 Notch 信号通路，协调这些分化过程，其失调可能导致癌症。通过γ-分泌酶抑制剂进行药理学抑制或 Notch 信号通路的遗传失活会导致增殖隐窝祖细胞因转化为有丝分裂后杯状细胞而完全丧失。碱性螺旋-环-螺旋转录因子 Math1 对于肠分泌细胞的分化是必需的。由于 Math1 和 Notch 信号在肠道稳态和肿瘤转化中的关键作用，我们试图确定调节肠干细胞分化为分泌细胞的遗传层次。在本文中，我们证明了 Notch 信号通路抑制后，肠干细胞向杯状细胞的转化需要 Math1。
