A novel mechanism for regulating clonal propagation of mouse ES cells
A novel mechanism for regulating clonal propagation of mouse ES cells
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DOI：
10.1111/j.1356-9597.2004.00736.x
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发表时间：
2004-05-01
期刊：
影响因子：
2.1
通讯作者：
Niwa, H
中科院分区：
文献类型：
--
作者：
Ogawa, K;Matsui, H;Niwa, H
胚胎干细胞的自我更新和分化受细胞外信号和基因表达调控的共同作用。为了表征控制这些事件的整个分子机制，我们首先建立了一个无饲养层和无血清的培养系统，在该系统中，小鼠ES细胞可以以克隆密度繁殖，并保持适当的多能性。需要补充促肾上腺皮质激素(ACTH)等多肽激素来去除血清，而这种现象中的关键事件可能是腺酰环化酶(AC)活性的抑制，因为它取代了这些多肽的作用。由于ES细胞本身产生相同的活性，这一发现表明了一种新的机制，即AC的激活限制了多能干细胞的克隆性繁殖。
Self-renewal and differentiation of embryonic stem (ES) cells are controlled by the combinatorial action of extracellular signals and regulation of gene expression. For characterizing the entire molecular mechanism governing these events, we first established a feeder- and serum-free culture system in which mouse ES cells could propagate in clonal density in keeping with proper pluripotency. Supplementation of peptide hormones such as adrenocorticotropic hormone (ACTH) is required to remove serum, and the key event in this phenomenon may be the inhibition of the adenylyl cyclase (AC) activity, as it replaces the effect of these peptides. Because ES cells themselves produce the same activity, the finding suggests a novel mechanism in which activation of AC restricts clonal propagation of pluripotent stem cells.