Self-renewal of embryonic stem cells by a small molecule
Self-renewal of embryonic stem cells by a small molecule
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DOI：
10.1073/pnas.0608156103
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发表时间：
2006-11-14
影响因子：
11.1
通讯作者：
Ding, Sheng
中科院分区：
文献类型：
--
作者：
Chen, Shuibing;Do, Jeong Tae;Ding, Sheng
进行基于细胞的化学文库筛选以鉴定控制ES细胞自我更新的小分子。发现了一种以前未表征的杂环，SC 1，其允许在不存在饲养细胞、血清和白血病抑制因子的情况下，在化学限定的条件下以未分化的多能状态繁殖鼠ES细胞。长期SC 1扩增的小鼠ES细胞可以在体外分化为三个初级胚层的细胞，也可以产生嵌合小鼠，并有助于在体内的生殖系。生化和细胞实验表明，SC1通过RasGAP和ERK 1的双重抑制起作用。这类分子不仅可以促进干细胞在研究和治疗中的实际应用，而且还可以为干细胞的复杂生物学提供以前未描述的见解。
A cell-based screen of chemical libraries was carried out to identify small molecules that control the self-renewal of ES cells. A previously uncharacterized heterocycle, SC1, was discovered that allows one to propagate murine ES cells in an undifferentiated, pluripotent state under chemically defined conditions in the absence of feeder cells, serum, and leukemia inhibitory factor. Long-term SC1-expanded murine ES cells can be differentiated into cells of the three primary germ layers in vitro and also can generate chimeric mice and contribute to the germ line in vivo. Biochemical and cellular experiments suggest that SC1 works through dual inhibition of RasGAP and ERK1. Molecules of this kind may not only facilitate practical applications of stem cells in research and therapy, but also provide previously undescribed insights into the complex biology of stem cells.