Dynamic microRNA Profiles of Hepatic Differentiated Human Umbilical Cord Lining-Derived Mesenchymal Stem Cells

被引：39

作者：

Cui, Lina ^{[1
]}

Zhou, Xinmin ^{[1
]}

Li, Jinge ^{[1
]}

Wang, Liuyi ^{[2
]}

Wang, Jingbo ^{[1
]}

Li, Qiang ^{[1
]}

Chu, Jindong ^{[1
]}

Zheng, Linhua ^{[1
]}

Wu, Qiong ^{[1
]}

Han, Zheyi ^{[1
]}

Shi, Yongquan ^{[1
]}

Han, Ying ^{[1
]}

Fan, Daiming ^{[1
]}

机构：

[1] Fourth Mil Med Univ, State Key Lab Canc Biol, Xijing Hosp Digest Dis, Xian 710032, Shaanxi Provinc, Peoples R China

[2] Yanan Univ, Dept Gastroenterol, Affiliated Hosp, Yanan, Shaanxi Provinc, Peoples R China

来源：

PLOS ONE | 2012年 / 7卷 / 09期

基金：

中国国家自然科学基金;

关键词：

HEPATOCYTE-LIKE CELLS; LIVER-REGENERATION; STROMAL CELLS; PROLIFERATION; PLURIPOTENCY; MOUSE;

D O I：

10.1371/journal.pone.0044737

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

070301 [无机化学]; 070403 [天体物理学]; 070507 [自然资源与国土空间规划学]; 090105 [作物生产系统与生态工程];

摘要：

Despite the extensive hepatic differentiation potential of human umbilical cord lining-derived mesenchymal stem cells (hUC-MSC), little is known about the molecular mechanisms of hUC-MSC differentiation. At the post-transcriptional level, microRNAs are key players in the control of cell fate determination during differentiation. In this study, we aimed to identify microRNAs involved in the hepatic differentiation of hUC-MSCs. After successfully isolating hUC-MSCs, we induced hepatocyte formation in vitro with growth factors. After 26 days of induction, hUC-MSCs could express hepatocyte-specific genes, synthesize urea and glycogen and uptake low-density lipoprotein. Cellular total RNA from hUC-MSCs and hepatic differentiated hUC-MSCs was collected at 7 time points, including 2 days, 6 days, 10 days, 14 days, 22 days and 26 days, for microRNA microarray analysis. Dynamic microRNA profiles were identified that did not overlap or only partially overlapped with microRNAs reported to be involved in human liver development, hepatocyte regeneration or hepatic differentiation of liver-derived progenitor cells. A total of 61 microRNAs among 1205 human and 144 human viral microRNAs displayed consistent changes and were altered at least 2-fold between hUC-MSCs and hepatic differentiated hUC-MSCs. Among these microRNAs, 25 were over-expressed; this over-expression occurred either gradually or increased sharply and was maintained at a high level. A total of 36 microRNAs were under-expressed, with an expression pattern similar to that of the over-expressed microRNAs. The expression of the altered expressed microRNAs was also confirmed by quantitative reverse-transcription polymerase chain reaction. We also found that microRNAs involved in hepatic differentiation were not enriched in hepatocyte or hepatocellular carcinoma cells and can potentially target liver-enriched transcription factors and genes. The elucidation of the microRNA profile during the hepatic differentiation of hUC-MSCs provides the basis for clarifying the role of microRNAs in hUC-MSC hepatic differentiation and specific microRNA selection for the conversion of hUC-MSCs to hepatocytes.

引用

页数：11

共 21 条

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