Roden Christine, Lu Jun
Department of Genetics, Yale University School of Medicine, New Haven, Connecticut 06510, USA; Yale Stem Cell Center, Yale Cancer Center, New Haven, Connecticut, 06520, USA; Graduate Program in Biological and Biomedical Sciences, Yale University, New Haven, Connecticut 06510, USA.
Department of Genetics, Yale University School of Medicine, New Haven, Connecticut 06510, USA; Yale Stem Cell Center, Yale Cancer Center, New Haven, Connecticut, 06520, USA; Yale Center for RNA Science and Medicine, New Haven, Connecticut, 06520, USA.
Curr Stem Cell Rep. 2016 Sep;2(3):183-196. doi: 10.1007/s40778-016-0057-1. Epub 2016 Jul 1.
Studies on hematopoietic stem cells (HSCs) and leukemia stem cells (LSCs) have helped to establish the paradigms of normal and cancer stem cell concepts. For both HSCs and LSCs, specific gene expression programs endowed by their epigenome functionally distinguish them from their differentiated progenies. MicroRNAs (miRNAs), as a class of small non-coding RNAs, act to control post-transcriptional gene expression. Research in the past decade has yielded exciting findings elucidating the roles of miRNAs in control of multiple facets of HSC and LSC biology. Here we review recent progresses on the functions of miRNAs in HSC emergence during development, HSC switch from a fetal/neonatal program to an adult program, HSC self-renewal and quiescence, HSC aging, HSC niche, and malignant stem cells. While multiple different miRNAs regulate a diverse array of targets, two common themes emerge in HSC and LSC biology: miRNA mediated regulation of epigenetic machinery and cell signaling pathways. In addition, we propose that miRNAs themselves behave like epigenetic regulators, as they possess key biochemical and biological properties that can provide both stability and alterability to the epigenetic program. Overall, the studies of miRNAs in stem cells in the hematologic contexts not only provide key understandings to post-transcriptional gene regulation mechanisms in HSCs and LSCs, but also will lend key insights for other stem cell fields.
对造血干细胞（HSC）和白血病干细胞（LSC）的研究有助于建立正常和癌症干细胞概念的范例。对于HSC和LSC而言，其表观基因组赋予的特定基因表达程序在功能上使它们与其分化后代区分开来。微小RNA（miRNA）作为一类小的非编码RNA，作用于控制转录后基因表达。过去十年的研究取得了令人兴奋的发现，阐明了miRNA在控制HSC和LSC生物学多个方面的作用。在此，我们综述了miRNA在发育过程中HSC出现、HSC从胎儿/新生儿程序向成人程序转变、HSC自我更新与静止、HSC衰老、HSC微环境以及恶性干细胞等方面功能的最新进展。虽然多种不同的miRNA调控着各种各样的靶标，但在HSC和LSC生物学中出现了两个共同主题：miRNA介导的表观遗传机制调控和细胞信号通路调控。此外，我们提出miRNA本身的行为类似于表观遗传调控因子，因为它们具有关键的生化和生物学特性，可为表观遗传程序提供稳定性和可变性。总体而言，血液学背景下干细胞中miRNA的研究不仅为HSC和LSC转录后基因调控机制提供了关键认识，也将为其他干细胞领域提供关键见解。
