Whole transcriptomic sequencing of mouse, in vitro embryonic- and ex vivo adult-derived cardiac progenitor cells

Recent advancements in cell-based therapies for the treatment of cardiovascular disease (CVD) show continuing promise for the use of transplanted stem and cardiac progenitor cells (CPCs) to promote cardiac restitution. However, a detailed understanding of the molecular mechanisms that control the development of these cells remains incomplete and is critical for optimizing their use in such therapy. Long non-coding (lnc) RNA has recently emerged as a crucial class of regulatory molecules involved in directing a variety of critical biological and cellular processes including development, homeostasis and disease. As such, a rising body of evidence suggests that they also play key regulatory roles in CPC development, though many questions remain regarding the expression landscape and specific identity of lncRNA involved in this process. To address this, we performed whole transcriptome sequencing of two murine CPC populations – Nkx2-5 EmGFP reporter-sorted embryonic stem (ES) cell-derived and ex vivo, cardiosphere-derived – in an effort to characterize their lncRNA profiles and potentially identify novel CPC regulators. The resulting sequencing data revealed an enrichment in both CPC populations for a panel of previously-identified lncRNA genes associated with cardiac differentiation. Additionally, a total of 1,678 differentially expressed and as-of-yet unannotated, putative lncRNA genes were found to be enriched for in the two CPC populations relative to undifferentiated ES cells.

近年来用于治疗心血管疾病（cardiovascular disease, CVD）的细胞疗法取得了新进展，其通过移植干细胞与心脏祖细胞（cardiac progenitor cells, CPCs）促进心脏修复的应用前景持续向好。然而，人们对调控这些细胞发育的分子机制仍缺乏完整认知，而该认知对于优化其在该疗法中的应用至关重要。长链非编码RNA（long non-coding RNA, lncRNA）近年来被发现是一类关键的调控分子，参与调控包括发育、稳态及疾病在内的多种重要生物学与细胞过程。因此，越来越多的研究证据表明，长链非编码RNA在CPC发育中也发挥着关键调控作用，不过该过程中涉及的长链非编码RNA的表达谱与具体种类仍有诸多疑问有待解答。为解决这一问题，我们对两类小鼠CPC群体开展了全转录组测序：一类是经Nkx2-5 EmGFP报告基因分选的胚胎干细胞（embryonic stem cell, ES）来源群体，另一类是体外心肌球来源群体，以期表征它们的长链非编码RNA表达谱，并有望鉴定出新型CPC调控因子。测序结果显示，两类CPC群体均富集了一批已被报道与心脏分化相关的长链非编码RNA基因。此外，相较于未分化的胚胎干细胞，两类CPC群体中还存在共计1678个差异表达且尚未注释的推定长链非编码RNA基因。