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：
10.1101/143339
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发表时间：
2017
期刊：
影响因子：
--
通讯作者：
Lai A
中科院分区：
文献类型：
--
作者：
Lai A
根据单细胞表达分析和随后的实验来证明谱系关系，已经对真涡虫干细胞的异源性进行了分类。一些数据表明，尽管细胞周期中细胞之间的基因表达存在异质性，但实际上只有一个亚群，称为sigma neoblast，可以自我更新。在没有工具进行活体体内谱系分析的情况下，我们采用了另一种方法来提供定义自我更新干细胞群的独立证据。我们利用高度保守的凝聚素家族基因的作用，功能测定新生细胞自我更新的属性。凝聚蛋白参与形成适当凝聚的染色体以允许细胞分裂在有丝分裂期间进行，并且它们的废除抑制有丝分裂并可导致重复尝试分裂的细胞中基因组的重复内复制。我们发现，真涡虫只拥有凝聚素I复合体，这是正常干细胞功能所必需的。去除凝聚素功能导致干细胞快速耗竭，伴随着DNA含量增加的“巨”细胞的出现。使用以前发现的异质性标记，我们表明，扩大的细胞总是从sigma类的neoblast人口，我们从来没有观察到证据的其他neoblast亚类的endorefersion。总的来说，我们的数据证实了凝聚素对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σ-neoblast能够进行多轮细胞分裂，从而自我更新。
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.
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DOI：
10.1126/science.1178712
发表时间：
2009-12-04
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Rink JC;Gurley KA;Elliott SA;Sánchez Alvarado A
通讯作者：
Sánchez Alvarado A
影响因子：
11.8
作者：
Tanaka, Elly M.;Reddien, Peter W.
通讯作者：
Reddien, Peter W.
影响因子：
3.3
作者：
Ouspenski, II;Cabello, OA;Brinkley, BR
通讯作者：
Brinkley, BR
对涡虫干细胞室进行 FACS 分析作为了解再生机制的工具。
影响因子：
--
作者：
B. T. Romero;Deborah J. Evans;A. Aboobaker
通讯作者：
A. Aboobaker
影响因子：
4.6
作者：
Tejada-Romero, Belen;Carter, Jean-Michel;Aboobaker, A. Aziz
通讯作者：
Aboobaker, A. Aziz