RNA sequencing reveals changes in the microRNAome of transdifferentiating hepatic stellate cells that are conserved between human and rat.
RNA sequencing reveals changes in the microRNAome of transdifferentiating hepatic stellate cells that are conserved between human and rat.
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RNA测序揭示了在人鼠之间保守的转分化肝星状细胞微小RNA组的变化。
DOI：
10.1038/s41598-020-78776-3
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发表时间：
2020-12-10
影响因子：
4.6
通讯作者：
Mann J
中科院分区：
文献类型：
--
作者：
Sabater L;Locatelli L;Oakley F;Hardy T;French J;Robinson SM;Sen G;Mann DA;Mann J
MicroRNA是一类长度约为22 nt的非编码RNA（ncRNA），在转录后水平调控基因的表达。在人类中已经描述了超过2000种microRNA，其中许多涉及人类病理学，包括组织纤维化。肝星状细胞（HSC）是病变肝脏中过量细胞外基质沉积的主要细胞贡献者，因此在肝纤维化的进展中是重要的。我们采用下一代测序技术来绘制在原代人HSC培养诱导转分化的详细时间过程中发生的microRNA表达的改变，这是纤维发生中的关键事件。此外，我们比较了人类HSC microRNA与大鼠HSC microRNA的谱，以鉴定那些在表达调节方面保守的分子。我们的分析表明，共有229个人类microRNA显示作为HSC转分化的结果改变表达，其中104个在起始阶段早期被调节。通常调节的microRNA靶向激酶、转录因子、染色质因子、细胞周期调节因子和生长因子。在大鼠HSC转分化过程中，162个microRNA的表达发生了变化，但只有17个发生了在人HSC中保守的变化。因此，我们的研究确定了纤维发生中HSC microRNA表达的广泛变化，但表明在将从啮齿动物HSC获得的数据转化为人类细胞中发生的事件时需要谨慎。
MicroRNAs are small (~ 22nt long) noncoding RNAs (ncRNAs) that regulate gene expression at the post-transcriptional level. Over 2000 microRNAs have been described in humans and many are implicated in human pathologies including tissue fibrosis. Hepatic stellate cells (HSC) are the major cellular contributors to excess extracellular matrix deposition in the diseased liver and as such are important in the progression of liver fibrosis. We employed next generation sequencing to map alterations in the expression of microRNAs occurring across a detailed time course of culture-induced transdifferentiation of primary human HSC, this a key event in fibrogenesis. Furthermore, we compared profiling of human HSC microRNAs with that of rat HSC so as to identify those molecules that are conserved with respect to modulation of expression. Our analysis reveals that a total of 229 human microRNAs display altered expression as a consequence of HSC transdifferentiation and of these 104 were modulated early during the initiation phase. Typically modulated microRNAs were targeting kinases, transcription factors, chromatin factors, cell cycle regulators and growth factors. 162 microRNAs changed in expression during transdifferentiation of rat HSC, however only 17 underwent changes that were conserved in human HSC. Our study therefore identifies widespread changes in the expression of HSC microRNAs in fibrogenesis, but suggests a need for caution when translating data obtained from rodent HSC to events occurring in human cells.
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