A comparative transcriptomic analysis reveals conserved features of stem cell pluripotency in planarians and mammals.
A comparative transcriptomic analysis reveals conserved features of stem cell pluripotency in planarians and mammals.
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DOI：
10.1002/stem.1144
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发表时间：
2012-08
期刊：
影响因子：
5.2
通讯作者：
Pearson, Bret J.
中科院分区：
文献类型：
--
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.
关键词：
许多长寿的动物物种需要成年干细胞在它们的一生中发挥作用。然而，无脊椎动物和脊椎动物中干细胞的转录本还没有被比较，因此，控制干细胞群体的祖先调节电路仍然缺乏明确的定义。在这项研究中，我们使用了来自高通量RNA测序的数据来比较来自脊椎动物的多能成体干细胞的转录本与人类和小鼠多能胚胎干细胞的转录本。从一组严格定义的4,432个在脊椎动物、小鼠和人类之间共享的同源基因中，我们确定了123个保守基因，它们在所有三个物种的干细胞中都有5倍的≥差异表达。在这个基因组的指导下，我们在成年浮游生物中进行RNAi筛选，以发现新的干细胞调节因子，我们发现这些调节因子影响干细胞相关的组织稳态、再生和干细胞维持功能。破坏这些过程的基因包括TBL3、PSD12、TTC27和RACK1的同源基因。从这些分析中，我们得出结论，通过比较不同物种的干细胞转录本，有可能发现在干细胞生物学中起作用的保守因素。这些结果提供了对哪些基因构成控制干细胞自我更新和多能性的祖先回路的洞察。
Many long-lived species of animals require the function of adult stem cells throughout their lives. However, the transcriptomes of stem cells in invertebrates and vertebrates have not been compared, and consequently, ancestral regulatory circuits that control stem cell populations remain poorly defined. In this study, we have used data from high-throughput RNA sequencing to compare the transcriptomes of pluripotent adult stem cells from planarians with the transcriptomes of human and mouse pluripotent embryonic stem cells. From a stringently defined set of 4,432 orthologs shared between planarians, mice and humans, we identified 123 conserved genes that are ≥5-fold differentially expressed in stem cells from all three species. Guided by this gene set, we used RNAi screening in adult planarians to discover novel stem cell regulators, which we found to affect the stem cell-associated functions of tissue homeostasis, regeneration, and stem cell maintenance. Examples of genes that disrupted these processes included the orthologs of TBL3, PSD12, TTC27, and RACK1. From these analyses, we concluded that by comparing stem cell transcriptomes from diverse species, it is possible to uncover conserved factors that function in stem cell biology. These results provide insights into which genes comprised the ancestral circuitry underlying the control of stem cell self-renewal and pluripotency.
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