The Hospital for Sick Children, Program in Developmental and Stem Cell Biology, University of Toronto, Toronto, Ontario, Canada.
Stem Cells. 2012 Aug;30(8):1734-45. doi: 10.1002/stem.1144.
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.
许多长寿动物的物种在其一生中都需要成体干细胞的功能。然而，尚未比较无脊椎动物和脊椎动物的干细胞转录组，因此，控制干细胞群体的祖先调控回路仍然定义不明确。在这项研究中，我们使用来自高通量 RNA 测序的数据，比较了涡虫多能成体干细胞的转录组与人类和小鼠多能胚胎干细胞的转录组。在严格定义的 4,432 个涡虫、小鼠和人类之间的直系同源物中，我们鉴定出了 123 个在这三种物种的所有干细胞中差异表达≥5 倍的保守基因。在这个基因集的指导下，我们在成年涡虫中使用 RNAi 筛选来发现新的干细胞调节剂，我们发现这些调节剂影响组织稳态、再生和干细胞维持的干细胞相关功能。破坏这些过程的基因包括 TBL3、PSD12、TTC27 和 RACK1 的直系同源物。从这些分析中，我们得出结论，通过比较来自不同物种的干细胞转录组，可以发现参与干细胞生物学的保守因子。这些结果提供了关于哪些基因构成控制干细胞自我更新和多能性的祖先调控回路的见解。
