Overexpression of microRNA-122 enhances in vitro hepatic differentiation of fetal liver-derived stem/progenitor cells

Overexpression of microRNA-122 enhances in vitro hepatic differentiation of fetal liver-derived stem/progenitor cells
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DOI:
10.1002/jcb.24499
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发表时间:
2013-07-01
影响因子:
4
通讯作者:
Chakraborti, Anuradha
Chakraborti, Anuradha
中科院分区:
生物学2区
文献类型:
--
作者:
Doddapaneni, Ravi .;Chawla, Yogesh K.;Chakraborti, Anuradha

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microRNA(miRNAs)是一类功能广泛的非编码RNA,参与多种生物学过程的调控。miRNA-122(miR-122)在人类肝脏中特异性且大量表达。然而,miR-122在胎肝干/祖细胞分化为肝细胞中的作用仍不清楚。本研究采用磁性细胞分选法富集表达CD 34 +/CD 117+双阳性的人胎肝干/祖细胞,并进行体外培养。发现miR-122的水平在特定的时间间隔增加。有趣的是,在肝细胞样细胞的分化过程中,miR-122表达的增加与肝细胞特异性基因的表达呈正相关。通过转染miR-122到富集的干/祖细胞中改善分化过程的状态。通过在胎肝干/祖细胞中过表达miR-122,肝特异性基因以及肝富集转录因子(LETF)的表达水平显著增加。因此,该研究描绘了肝脏特异性miR-122在胎肝干/祖细胞分化为肝细胞样细胞中的作用,其可用作产生丰富肝细胞的治疗靶分子。J.细胞。114:15751583,2013。(c)2013 Wiley Periodicals,Inc.
MicroRNAs (miRNAs) are a versatile class of tiny non-coding RNAs involved in regulation of various biological processes. miRNA-122 (miR-122) is specifically and abundantly expressed in human liver. However, the role of miR-122 in differentiation of fetal liver stem/progenitor cells into hepatocytes remains unclear. In this study, dual positive CD34+/CD117+ expressing human fetal liver stem/progenitor cells was enriched by magnetic cell sorting and cultured in vitro. The level of miR-122 was found to be increased at specific time intervals. Interestingly, during the differentiation process of hepatocyte-like cells, the increase in expression of miR-122 was positively correlated with expression of hepatocyte-specific genes. The status of differentiation process was improved by transfection of miR-122 into enriched stem/progenitor cells. The expression level of hepatic-specific genes as well as liver-enriched transcription factors (LETFs) was significantly increased by overexpression of miR-122 in fetal liver stem/progenitor cells. Thus, the study delineated the role of hepato-specific miR-122 in differentiation of fetal liver stem/progenitor cells into hepatocyte-like cells which could be used as a therapeutic target molecule to generate abundant hepatocytes. J. Cell. Biochem. 114: 15751583, 2013. (c) 2013 Wiley Periodicals, Inc.