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研究解构成纤维细胞逐步转化为神经元的命运
作者:小柯机器人 发布时间:2020/9/22 15:13:17

美国华盛顿大学医学院Andrew S. Yoo课题组通过MicroRNA解构人类成纤维细胞逐步转化为神经元的命运。该项研究成果发表在2020年9月21日的《细胞-干细胞》杂志上。

他们揭示了对microRNA miR-9 / 9 和miR-124(miR-9 / 9 -124)作为重编程剂的活性的见解,它们通过首先擦除成纤维细胞身份,并促进其协调人类成纤维细胞直接转化为运动神经元均匀过渡到神经元状态。

他们鉴定了KLF家族转录因子是miR-9 / 9 -124的直接靶基因,并表明其抑制作用对于擦除成纤维细胞的命运至关重要。随后获得神经元身份需要上调小核RNA RN7SK,从而诱导染色质区域的可访问性和神经元基因激活,从而将细胞推向神经元状态。 他们的研究定义了microRNA介导的重编程级联反应中的确定性成分。

据悉,细胞命运转换通常需要重新编程效应子,以引入靶细胞类型的命运程序并擦除起始细胞群的身份。

附:英文原文

Title: Deconstructing Stepwise Fate Conversion of Human Fibroblasts to Neurons by MicroRNAs

Author: Kitra Cates, Matthew J. McCoy, Ji-Sun Kwon, Yangjian Liu, Daniel G. Abernathy, Bo Zhang, Shaopeng Liu, Paul Gontarz, Woo Kyung Kim, Shawei Chen, Wenjun Kong, Joshua N. Ho, Kyle F. Burbach, Harrison W. Gabel, Samantha A. Morris, Andrew S. Yoo

Issue&Volume: 2020-09-21

Abstract: Cell-fate conversion generally requires reprogramming effectors to both introducefate programs of the target cell type and erase the identity of starting cell population.Here, we reveal insights into the activity of microRNAs miR-9/9 and miR-124 (miR-9/9-124) as reprogramming agents that orchestrate direct conversion of human fibroblastsinto motor neurons by first eradicating fibroblast identity and promoting uniformtransition to a neuronal state in sequence. We identify KLF-family transcription factorsas direct target genes for miR-9/9-124 and show their repression is critical for erasing fibroblast fate. Subsequentgain of neuronal identity requires upregulation of a small nuclear RNA, RN7SK, which induces accessibilities of chromatin regions and neuronal gene activationto push cells to a neuronal state. Our study defines deterministic components in the microRNA-mediated reprogramming cascade.

DOI: 10.1016/j.stem.2020.08.015

Source: https://www.cell.com/cell-stem-cell/fulltext/S1934-5909(20)30411-2

期刊信息

Cell Stem Cell:《细胞—干细胞》,创刊于2007年。隶属于细胞出版社,最新IF:21.464
官方网址:https://www.cell.com/cell-stem-cell/home
投稿链接:https://www.editorialmanager.com/cell-stem-cell/default.aspx