INHIBITION OF PLURIPOTENTIAL EMBRYONIC STEM-CELL DIFFERENTIATION BY PURIFIED POLYPEPTIDES
INHIBITION OF PLURIPOTENTIAL EMBRYONIC STEM-CELL DIFFERENTIATION BY PURIFIED POLYPEPTIDES
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DOI：
10.1038/336688a0
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发表时间：
1988-12-15
期刊：
影响因子：
64.8
通讯作者：
ROGERS, D
中科院分区：
文献类型：
--
作者：
SMITH, AG;HEATH, JK;ROGERS, D
小鼠胚胎干细胞是直接从早期胚胎1，2建立的多能细胞系，在重新整合到正常胚胎后，可以将分化的后代贡献给所有的成年组织，包括生殖细胞系3。它们既为转基因动物的产生提供了细胞载体4，也为鉴定早期发育过程中控制分化过程的多肽因子提供了有用的系统5。特别是，以水牛大鼠肝细胞为条件的培养液中含有一种多肽因子，即ES细胞分化抑制活性(DIA)，它能在体外特异性地抑制ES细胞的自发分化，从而允许它们在没有异种饲养细胞的情况下作为同质干细胞群体生长6。ES细胞的多能性，包括产生功能配子的能力，在作为DIA7来源的水牛大鼠肝脏培养液中长期培养后得到保存。在此，我们报道了纯化的DIA在结构和功能上与最近发现的造血调节因子人白细胞介素DA细胞8，9和白血病抑制因子10有关。因此，DIA和人白介素DA/白血病抑制因子被确定为相关的多功能调节因子，在早期胚胎干细胞和造血干细胞系统中都具有不同的生物学活性。
Murine embryonic stem (ES) cells are pluripotent cell lines established directly from the early embryo1,2which can contribute differentiated progeny to all adult tissues, including the germ-cell lineage3, after re-incorporation into the normal embryo. They provide both a cellular vector for the generation of transgenic animals4and a useful system for the identification of polypeptide factors controlling differentiation processes in early development5. In particular, medium conditioned by Buffalo rat liver cells contains a polypeptide factor, ES cell differentiation inhibitory activity (DIA), which specifically suppresses the spontaneous differentiation of ES cellsin vitro, thereby permitting their growth as homogeneous stem cell populations in the absence of heterologous feeder cells6. ES cell pluripotentiality, including the ability to give rise to functional gametes, is preserved after prolonged culture in Buffalo rat liver media as a source of DIA7. Here, we report that purified DIA is related in structure and function to the recently identified haemopoetic regulatory factors human interleukin for DA cells8,9and leukaemia inhibitory factor10. DIA and human interleukin DA/leukaemia inhibitory factor have thus been identified as related multifunctional regulatory factors with distinct biological activities in both early embryonic and haemopoetic stem cell systems.