Foshay Kara M, Gallicano G Ian
Georgetown University Medical Center, Department of Biochemistry & Molecular & Cellular Biology, Washington, DC, USA.
Curr Stem Cell Res Ther. 2007 Dec;2(4):264-71. doi: 10.2174/157488807782793781.
MicroRNAs (miRNAs) are a newly discovered, yet powerful mechanism for regulating protein expression via mRNA translational inhibition. Loss of all miRNA function within mice leads to embryonic lethality with a loss of the stem cell population in the epiblast and failure to form a primitive streak. These data suggest that miRNAs play a major role in embryonic development. As critical regulation of protein expression is also important for controlling the balance between self-renewal and differentiation in stem cells, the study of miRNAs within this model system is rapidly expanding. New data suggest that stem cells have discrete miRNA expression profiles, which may account for, or contribute to, the intrinsic stem cell properties of self-renewal and pluripotency. Specifically, miRNAs have been implicated in downregulation of cell cycle checkpoint proteins during germ stem cell division. Other data demonstrate that changes in miRNA expression can promote or inhibit stem or progenitor cell differentiation within different cell lineages, including hematopoietic cells, cardiomyocytes, myoblasts, and neural cells. In this review we detail the established functional roles of miRNAs in the embryonic and adult stem cell model systems. Finally, we explore new techniques that exploit endogenous miRNA processing and function for applications in basic and clinical research.
微小RNA（miRNA）是一种新发现的、通过抑制mRNA翻译来调控蛋白质表达的强大机制。小鼠体内所有miRNA功能的丧失会导致胚胎致死，同时上胚层干细胞群缺失且无法形成原条。这些数据表明miRNA在胚胎发育中起主要作用。由于蛋白质表达的关键调控对于控制干细胞自我更新和分化之间的平衡也很重要，因此在这个模型系统中对miRNA的研究正在迅速扩展。新数据表明干细胞具有离散的miRNA表达谱，这可能解释或促成了自我更新和多能性的内在干细胞特性。具体而言，miRNA与生殖干细胞分裂过程中细胞周期检查点蛋白的下调有关。其他数据表明，miRNA表达的变化可以促进或抑制不同细胞谱系（包括造血细胞、心肌细胞、成肌细胞和神经细胞）中干细胞或祖细胞的分化。在这篇综述中，我们详细阐述了miRNA在胚胎和成人干细胞模型系统中已确立的功能作用。最后，我们探索利用内源性miRNA加工和功能的新技术，以应用于基础和临床研究。
