Planarian stem cell transcriptome

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 (RNA-Seq) 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 composed the ancestral circuitry underlying the control of stem cell self-renewal and pluripotency.

诸多长寿动物物种在整个生命周期中均依赖成体干细胞的功能维持。然而，目前尚无针对无脊椎动物与脊椎动物干细胞转录组的比较研究，因此调控干细胞群体的祖先调控环路仍未得到清晰阐明。本研究借助高通量RNA测序（RNA-Seq）产生的数据，将涡虫（planarians）的多能成体干细胞转录组，与人类及小鼠的多能胚胎干细胞转录组进行了对比。我们从涡虫、小鼠与人类共有的4432个严格筛选的直系同源基因（orthologs）集合中，鉴定出123个保守基因，这三类物种的干细胞中该类基因的差异表达倍数均≥5倍。基于该基因集，我们在成年涡虫中开展RNA干扰（RNAi）筛选，以挖掘新型干细胞调控因子；最终发现这些因子可影响与干细胞相关的组织稳态、再生及干细胞维持功能。能够干扰上述过程的基因示例包括TBL3、PSD12、TTC27及RACK1的直系同源基因。基于上述分析，我们得出结论：通过对比不同物种的干细胞转录组，可揭示在干细胞生物学中发挥功能的保守因子。本研究结果为解析调控干细胞自我更新与多能性的祖先调控环路的基因组成提供了新见解。