RNA 测序揭示了人源和大鼠转分化肝星状细胞中 microRNAome 的变化,这些变化在两者之间是保守的。
RNA sequencing reveals changes in the microRNAome of transdifferentiating hepatic stellate cells that are conserved between human and rat.
机构信息
Newcastle Fibrosis Research Group, Bioscience Institute, Faculty of Medical Sciences, Newcastle University, 4th Floor, William Leech Building, Framlington Place, Newcastle upon Tyne, NE2 4HH, UK.
Department of Hepatobiliary Surgery, Newcastle Upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, UK.
出版信息
Sci Rep. 2020 Dec 10;10(1):21708. doi: 10.1038/s41598-020-78776-3.
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.
微小 RNA 是小的 (~22nt 长) 非编码 RNA (ncRNAs),在转录后水平调节基因表达。在人类中已经描述了超过 2000 种微小 RNA,其中许多与包括组织纤维化在内的人类病理有关。肝星状细胞 (HSC) 是肝脏疾病中外源性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非常重要。我们采用下一代测序技术来绘制在原代人 HSC 培养诱导的转分化过程中发生的微小 RNA 表达变化图谱,这是纤维化发生的关键事件。此外,我们比较了人 HSC 微小 RNA 的分析与大鼠 HSC 的分析,以确定那些在表达调控方面保守的分子。我们的分析表明,共有 229 个人类微小 RNA 的表达因 HSC 转分化而改变,其中 104 个在起始阶段早期被调节。典型调节的微小 RNA 针对激酶、转录因子、染色质因子、细胞周期调节剂和生长因子。162 个微小 RNA 在大鼠 HSC 的转分化过程中表达发生变化,但只有 17 个在人 HSC 中发生了保守的变化。因此,我们的研究确定了纤维化过程中 HSC 微小 RNA 表达的广泛变化,但在将从啮齿动物 HSC 获得的数据转化为人类细胞中发生的事件时,需要谨慎。