The abrogation of condensin function provides independent evidence for defining the self-renewing population of pluripotent stem cells.
The abrogation of condensin function provides independent evidence for defining the self-renewing population of pluripotent stem cells.
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凝缩蛋白功能的废除为定义多能干细胞的自我更新群体提供了独立的证据。
DOI：
10.1016/j.ydbio.2017.07.023
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发表时间：
2018-01-15
影响因子：
2.7
通讯作者：
Aboobaker AA
中科院分区：
文献类型：
--
作者：
Lai AG;Kosaka N;Abnave P;Sahu S;Aboobaker AA
根据单细胞表达分析和随后的实验来证明谱系关系，已经对脊椎动物干细胞的异质性进行了分类。一些数据表明，尽管在细胞周期中细胞间的基因表达存在异质性，但实际上只有一个亚群，即Sigma新生母细胞，能够自我更新。在没有进行活体谱系分析的工具的情况下，我们采取了另一种方法，为定义自我更新的干细胞群体提供了独立的证据。我们利用高度保守的凝聚素家族基因的作用来从功能上分析新生细胞的自我更新特性。凝聚素参与形成适当的浓缩染色体，以便在有丝分裂期间进行细胞分裂，它们的去除会抑制有丝分裂，并可能导致反复尝试分裂的细胞中基因组的重复内复制。我们发现，行星动物只拥有凝集素I复合体，这是正常干细胞功能所必需的。凝聚素功能的丧失导致干细胞迅速枯竭，并伴随着DNA含量增加的巨大细胞的出现。使用以前发现的异质性标记，我们发现放大的细胞总是来自新胚细胞群体的sigma类，我们从未观察到其他新胚细胞亚类的内复制的证据。总体而言，我们的数据证实了凝集素对于干细胞的维持是必不可少的，并提供了独立的证据，表明只有Sigma-新生细胞才有能力进行多轮细胞分裂，从而进行自我更新。凝集素I复合体转录本存在于Sigma、Gamma和Zeta新母细胞干细胞中。凝集素成分的耗尽会导致干细胞耗尽和内复制。通过内复制形成的“巨细胞”只对Sigma新生细胞标志物呈阳性反应。西格玛新母细胞是唯一一群能够自我更新的脊椎动物细胞。
Heterogeneity of planarian stem cells has been categorised on the basis of single cell expression analyses and subsequent experiments to demonstrate lineage relationships. Some data suggest that despite heterogeneity in gene expression amongst cells in the cell cycle, in fact only one sub-population, known as sigma neoblasts, can self-renew. Without the tools to perform live in vivo lineage analysis, we instead took an alternative approach to provide independent evidence for defining the self-renewing stem cell population. We exploited the role of highly conserved condensin family genes to functionally assay neoblast self-renewal properties. Condensins are involved in forming properly condensed chromosomes to allow cell division to proceed during mitosis, and their abrogation inhibits mitosis and can lead to repeated endoreplication of the genome in cells that make repeated attempts to divide. We find that planarians possess only the condensin I complex, and that this is required for normal stem cell function. Abrogation of condensin function led to rapid stem cell depletion accompanied by the appearance of ‘giant’ cells with increased DNA content. Using previously discovered markers of heterogeneity we show that enlarged cells are always from the sigma-class of the neoblast population and we never observe evidence for endoreplication for the other neoblast subclasses. Overall, our data establish that condensins are essential for stem cell maintenance and provide independent evidence that only sigma-neoblasts are capable of multiple rounds of cell division and hence self-renewal. Condensin I complex transcripts are present in sigma, gamma and zeta neoblast stem cells. Depletion of condensin components causes stem cell depletion and endoreplication. ‘Giant’ cells that form by endoreplication are only ever positive for sigma neoblast markers. sigma neoblasts are the only population of planarian cells capable of self-renewal.
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影响因子：
--
作者：
King RS;Newmark PA
通讯作者：
Newmark PA
影响因子：
--
作者：
Lauter G;Söll I;Hauptmann G
通讯作者：
Hauptmann G
DOI：
10.1083/jcb.200908026
发表时间：
2010-02-22
期刊：
The Journal of cell biology
影响因子：
--
作者：
Fazzio TG;Panning B
通讯作者：
Panning B
影响因子：
5.2
作者：
Labbe, Roselyne M.;Irimia, Manuel;Currie, Ko W.;Lin, Alexander;Zhu, Shu Jun;Brown, David D. R.;Ross, Eric J.;Voisin, Veronique;Bader, Gary D.;Blencowe, Benjamin J.;Pearson, Bret J.
通讯作者：
Pearson, Bret J.
影响因子：
10.5
作者：
Hu, Guang;Kim, Jonghwan;Elledge, Stephen J.
通讯作者：
Elledge, Stephen J.