Clonal and population analyses demonstrate that an EGF-responsive mammalian embryonic CNS precursor is a stem cell

Clonal and population analyses demonstrate that an EGF-responsive mammalian embryonic CNS precursor is a stem cell
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DOI:
10.1006/dbio.1996.0090
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发表时间:
1996-04-10
影响因子:
2.7
通讯作者:
Weiss, S
Weiss, S
中科院分区:
生物学3区
文献类型:
--
作者:
Reynolds, BA;Weiss, S

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在胚胎纹状体的培养中,我们之前报道过EGF诱导单个前体细胞的增殖,这些前体细胞产生未分化的细胞球,可以产生神经元和胶质细胞。我们在此报告,在体外,这些胚胎前体细胞表现出特性,并满足干细胞的代表性标准。egf应答细胞能够产生哺乳动物中枢神经系统神经元、星形胶质细胞和少突胶质细胞的三种主要表型。从初代球衍生的初代球和次生扩增无性系中,约90%包含所有三种细胞类型。EGF生成球的频率增加,从原代培养的1%增加到二次培养的接近20%,并且从单个原代球中可以产生大量克隆衍生的二次球,这表明EGF诱导了前体细胞本身的更新和扩增。在群体研究中,egf反应细胞经过10次传代,导致细胞数量增加10(7)倍,但没有失去其增殖和多谱系潜力。因此,本研究通过克隆和体外群体分析,首次证明了哺乳动物中枢神经系统干细胞在一种确定的生长因子(EGF)的作用下增殖,并产生中枢神经系统的三种主要细胞类型。(C) 1996学术出版社,Inc.
In cultures of embryonic striatum, we previously reported that EGF induces the proliferation of single precursor cells, which give rise to spheres of undifferentiated cells that can generate neurons and glia. We report here that, in vitro, these embryonic precursor cells exhibit properties and satisfy criteria representative of stem cells. The EGF-responsive cell was able to generate the three major phenotypes of the mammalian CNS-neurons, astrocytes, and oligodendrocytes. Approximately 90% of both primary spheres and secondary expanded clones, derived from the primary spheres, contained all three cell types. The increase in frequency of EGF-generated spheres, from 1% in primary culture to close to 20% in secondary culture, and the large number of clonally derived secondary spheres that could be generated from a single primary sphere indicate that EGF induces both renewal and expansion of the precursor cell itself. In population studies, the EGF-responsive cells were carried through 10 passages, resulting in a 10(7)-fold increase in cell number, without losing their proliferative and multilineage potential. Thus, this study describes the first demonstration, through clonal and population analyses in vitro, of a mammalian CNS stem cell that proliferates in response to an identified growth factor (EGF) and produces the three principal cell types of the CNS. (C) 1996 Academic Press, Inc.