MYELOID-LEUKEMIA INHIBITORY FACTOR MAINTAINS THE DEVELOPMENTAL POTENTIAL OF EMBRYONIC STEM-CELLS

MYELOID-LEUKEMIA INHIBITORY FACTOR MAINTAINS THE DEVELOPMENTAL POTENTIAL OF EMBRYONIC STEM-CELLS
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DOI:
10.1038/336684a0
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发表时间:
1988-12-15
期刊:
影响因子:
64.8
通讯作者:
GOUGH, NM
GOUGH, NM
中科院分区:
综合性期刊1区
文献类型:
--
作者:
WILLIAMS, RL;HILTON, DJ;GOUGH, NM

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胚胎干细胞(ES)是偏性胞体的全能产物1,2,可以在体外培养和操作,然后返回到胚胎环境中,在那里它们正常发育,并可以促进所有细胞系3 -9。在体外维持干细胞表型需要成纤维细胞饲养层的存在1,2,10或由许多来源产生的可溶性因子,分化抑制活性(DIA)的存在5,11,12;在DIA缺乏的情况下,ES细胞分化为各种细胞类型。我们最近注意到部分纯化的DIA和造血调节剂骨髓性白血病抑制因子(LIF)之间的一些相似性,LIF是一种诱导Ml骨髓性白血病细胞分化的分子,我们最近已经纯化、克隆和表征了LIF 13 -18。我们在这里证明,纯化的重组LIF可以取代DIA在维持全能ES细胞系,保留形成嵌合小鼠的潜力。
Embryonic stem (ES) cells, the totipotent outgrowths of bias-tocysts1,2, can be cultured and manipulatedin vitroand then returned to the embryonic environment where they develop normally and can contribute to all cell lineages3–9. Maintenance of the stem-cell phenotypein vitrorequires the presence of a feeder layer of fibroblasts1,2,10or of a soluble factor, differentiation inhibitory activity (DIA) produced by a number of sources5,11,12; in the absence of DIA the ES cells differentiate into a wide variety of cell types. We recently noted several similarities between partially purified DIA and a haemopoietic regulator, myeloid leukaemia inhibitory factor (LIF), a molecule which induces differentiation in Ml myeloid leukaemic cells and which we have recently purified, cloned and characterized13–18. We demonstrate here that purified, recombinant LIF can substitute for DIA in the maintenance of totipotent ES cell lines that retain the potential to form chimaeric mice.