Department of Biological Repositories, Zhongnan Hospital of Wuhan University, Frontier Science Center for Immunology and Metabolism, Medical Research Institute, Wuhan University, Wuhan, China.
State Key Laboratory of Biocatalysis and Enzyme Engineering, School of Life Science, Hubei University, Wuhan, China.
FASEB J. 2021 Apr;35(4):e21438. doi: 10.1096/fj.202002278R.
Pluripotency maintenance and lineage differentiation are two major characteristics of human embryonic and induced pluripotent stem cells. The determination of self-renewal or differentiation is under the exquisite control of the gene regulatory network, which is composed of transcription factors, signaling pathways, metabolic factors, chromatin or histone modifiers, miRNAs, and lncRNAs. Growing evidence has shown that long noncoding RNAs (lncRNAs) play important roles in epigenetic, transcriptional, and posttranscriptional gene regulation during the cell fate determination of pluripotent stem cells. Here, we summarize recent reports of lncRNA functions in pluripotency maintenance/exit and the early germ layer specification of human pluripotent stem cells. We also illustrate four major lncRNA functional mechanisms according to different types of cofactors: chromatin or histone modifiers, transcription factors, canonical and noncanonical RNA-binding proteins, and miRNAs. Further understanding of lncRNA-based regulation will provide more insights into the drivers manipulating cell fate and promote the therapeutic and research potential of human embryonic and induced pluripotent stem cells.
多能性维持和谱系分化是人类胚胎和诱导多能干细胞的两个主要特征。自我更新或分化的决定受基因调控网络的精细控制，该网络由转录因子、信号通路、代谢因子、染色质或组蛋白修饰物、miRNA 和 lncRNA 组成。越来越多的证据表明，长非编码 RNA（lncRNA）在多能干细胞的细胞命运决定过程中，在表观遗传、转录和转录后基因调控中发挥重要作用。在这里，我们总结了 lncRNA 在多能性维持/退出和人类多能干细胞早期胚层特化中的功能的最新报告。我们还根据不同类型的辅助因子说明了 lncRNA 的四种主要功能机制：染色质或组蛋白修饰物、转录因子、典型和非典型 RNA 结合蛋白以及 miRNA。进一步了解基于 lncRNA 的调控将为操纵细胞命运的驱动因素提供更多的见解，并促进人类胚胎和诱导多能干细胞的治疗和研究潜力。
