Interdisciplinary Centre for Clinical Research Aachen, RWTH Aachen University, Aachen, Germany.
PLoS One. 2011;6(10):e25809. doi: 10.1371/journal.pone.0025809. Epub 2011 Oct 3.
MicroRNA (miRNA) plays a critical role in a wide variety of biological processes. Profiling miRNA expression during differentiation of embryonic stem cells will help to understand the regulation pathway of differentiation, which in turn may elucidate disease mechanisms. The identified miRNAs could then serve as a new group of possible therapeutic targets. In the present paper, miRNA expression profiles were determined during cardiomyocyte-specific differentiation and maturation of murine embryonic stem (ES) cells. For this purpose a homogeneous cardiomyocyte population was generated from a transgenic murine ES cell line. Two high throughput array platforms (Affymetrix and Febit) were used for miRNA profiling in order to compare the effect of the platforms on miRNA profiling as well as to increase the validity of target miRNA identification. Four time points (i.e. day 0, day 12, day 19 and day 26) were chosen for the miRNA profiling study, which corresponded to different stages during cardiomyocyte-specific differentiation and maturation. Fifty platform and pre-processing method-independent miRNAs were identified as being regulated during the differentiation and maturation processes. The identification of these miRNAs is an important step for characterizing and understanding the events involved in cardiomyocyte-specific differentiation of ES cells and may also highlight candidate target molecules for therapeutic purposes.
微小 RNA(miRNA)在广泛的生物过程中起着至关重要的作用。对胚胎干细胞分化过程中的 miRNA 表达谱进行分析,有助于理解分化的调控途径,进而可能阐明疾病的发病机制。鉴定出的 miRNAs 随后可能成为一组新的可能的治疗靶点。本研究旨在确定小鼠胚胎干细胞(ES 细胞)向心肌细胞特异性分化和成熟过程中的 miRNA 表达谱。为此,我们从一个转基因的小鼠 ES 细胞系中生成了一个同质的心肌细胞群体。使用两种高通量微阵列平台(Affymetrix 和 Febit)进行 miRNA 分析,以比较平台对 miRNA 分析的影响,从而提高靶 miRNA 鉴定的有效性。选择了四个时间点(即第 0 天、第 12 天、第 19 天和第 26 天)进行 miRNA 分析,这对应于心肌细胞特异性分化和成熟过程中的不同阶段。鉴定出 50 个与平台和预处理方法无关的 miRNA 在分化和成熟过程中受到调控。鉴定这些 miRNA 是对 ES 细胞向心肌细胞特异性分化过程中涉及的事件进行特征描述和理解的重要步骤,也可能突出治疗目的的候选靶分子。