CD133 (Prominin) negative human neural stem cells are clonogenic and tripotent.

CD133 (Prominin) negative human neural stem cells are clonogenic and tripotent.
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DOI:
10.1371/journal.pone.0005498
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发表时间:
2009
期刊:
影响因子:
3.7
通讯作者:
Smith A
Smith A
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Sun Y;Kong W;Falk A;Hu J;Zhou L;Pollard S;Smith A

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CD 133(Prominin)被广泛用作从正常脑或肿瘤组织中鉴定和分离神经前体细胞的标记物。然而,CD 133在神经前体细胞中组成型表达的假设尚未得到检验。在这项研究中,我们证明,CD 133和第二个标志物CD 15在均匀未分化的人神经干细胞(NS)培养物中异质表达。在通过流式细胞术分级分离后,在对任一标志物呈阴性或阳性的群体中发现克隆原性三能细胞。我们进一步表明,CD 133在mRNA水平下调缺乏CD 133免疫反应性的细胞。细胞周期分析显示,CD 133阴性细胞主要位于G1/G 0期,而CD 133阳性细胞主要位于S、G2或M期。类似的模式在小鼠NS细胞系中是明显的。然而,与小鼠NS细胞相比,人NS细胞培养物中CD 133阴性细胞的比例增加,并显示出更长的倍增时间。这可能部分反映了人类NS细胞中缓慢或非循环细胞的亚群,因为我们发现约5%的细胞在14天的标记期内不摄取BrdU。非增殖NS细胞保持未分化,并且它们中的至少一些能够重新进入细胞周期和随后的连续扩增。克隆性神经干细胞的显著部分缺乏已建立的标记物CD 133和CD 15,并且这些细胞中的一些可能是休眠的或缓慢循环的,这一发现对鉴定和分离神经干细胞和脑癌干细胞的方法具有影响。我们的数据还表明,CD 133可能在G 0/G1期特异性下调,当该标志物用于识别和分离其他组织和癌症干细胞时,应考虑这一点。
CD133 (Prominin) is widely used as a marker for the identification and isolation of neural precursor cells from normal brain or tumor tissue. However, the assumption that CD133 is expressed constitutively in neural precursor cells has not been examined. In this study, we demonstrate that CD133 and a second marker CD15 are expressed heterogeneously in uniformly undifferentiated human neural stem (NS) cell cultures. After fractionation by flow cytometry, clonogenic tripotent cells are found in populations negative or positive for either marker. We further show that CD133 is down-regulated at the mRNA level in cells lacking CD133 immunoreactivity. Cell cycle profiling reveals that CD133 negative cells largely reside in G1/G0, while CD133 positive cells are predominantly in S, G2, or M phase. A similar pattern is apparent in mouse NS cell lines. Compared to mouse NS cells, however, human NS cell cultures harbour an increased proportion of CD133 negative cells and display a longer doubling time. This may in part reflect a sub-population of slow- or non-cycling cells amongst human NS cells because we find that around 5% of cells do not take up BrdU over a 14-day labelling period. Non-proliferating NS cells remain undifferentiated and at least some of them are capable of re-entry into the cell cycle and subsequent continuous expansion. The finding that a significant fraction of clonogenic neural stem cells lack the established markers CD133 and CD15, and that some of these cells may be dormant or slow-cycling, has implications for approaches to identify and isolate neural stem cells and brain cancer stem cells. Our data also suggest the possibility that CD133 may be specifically down-regulated during G0/G1, and this should be considered when this marker is used to identify and isolate other tissue and cancer stem cells.
人类胚胎干细胞,结肠癌和黑色素瘤细胞系中CD133表位的细胞周期依赖性变化。
DOI: 10.1158/0008-5472.can-08-0723
发表时间: 2008-10-01
期刊: CANCER RESEARCH
影响因子: 11.2
作者:
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通讯作者: Oshima, Robert G.
DOI: 10.1158/0008-5472.can-07-0183
发表时间: 2007-06-15
期刊: CANCER RESEARCH
影响因子: 11.2
作者:
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DOI: 10.1073/pnas.1734197100
发表时间: 2003-09-30
影响因子: 11.1
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发表时间: 2005-09
期刊: PLoS biology
影响因子: 9.8
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DOI: 10.1016/0304-3940(93)90748-a
发表时间: 1993-01-12
影响因子: 2.5
作者:
COROTTO, FS;HENEGAR, JA;MARUNIAK, JA
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