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新型单细胞测序方法阐明驱动ESC分化的组合信号途径
作者:小柯机器人 发布时间:2020/5/28 14:43:06

美国哈佛医学院Richard I. Sherwood、麻省理工学校David K. Gifford等研究人员合作,利用多重条形码单细胞RNA-Seq方法阐明了驱动ESC分化的组合信号通路。相关论文于2020年5月26日在线发表在《细胞—干细胞》上。

研究人员报道了条形码单细胞RNA测序(barRNA-seq),它可以通过用RNA“条形码”标记单个细胞,从而根据其接受的处理来鉴定它们,进而对细胞扰动进行系统性探索。研究人员应用barRNA-seq来同时操纵多达七个发育途径,并研究对胚胎干细胞(ESC)胚层分化和中胚层分化的影响,从而揭示了信号通路激活对基因表达的组合作用。
 
研究人员进一步开发了一个数据驱动的框架,用于鉴定促使细胞向不同特定命运分化的组合信号,包括现有的scRNA-seq原肠运动图谱中的途径,并使用这种方法来指导ESC分化为类脊索群体。研究人员认为barRNA-seq在研究和了解协同信号通路如何驱动细胞命运改变方面具有广泛的用途。
 
据了解,干细胞分化方案的经验优化既耗时又费力,并且通常不会全面研究所有相关的信号途径。
 
附:英文原文

Title: A Multiplexed Barcodelet Single-Cell RNA-Seq Approach Elucidates Combinatorial Signaling Pathways that Drive ESC Differentiation

Author: Grace Hui Ting Yeo, Lin Lin, Celine Yueyue Qi, Minsun Cha, David K. Gifford, Richard I. Sherwood

Issue&Volume: 2020-05-26

Abstract: Empirical optimization of stem cell differentiation protocols is time consuming, islaborintensive, and typically does not comprehensively interrogate all relevant signalingpathways. Here we describe barcodelet single-cell RNA sequencing (barRNA-seq), whichenables systematic exploration of cellular perturbations by tagging individual cellswith RNA “barcodelets” to identify them on the basis of the treatments they receive.We apply barRNA-seq to simultaneously manipulate up to seven developmental pathwaysand study effects on embryonic stem cell (ESC) germ layer specification and mesodermalspecification, uncovering combinatorial effects of signaling pathway activation ongene expression. We further develop a data-driven framework for identifying combinatorialsignaling perturbations that drive cells toward specific fates, including severalannotated in an existing scRNA-seq gastrulation atlas, and use this approach to guideESC differentiation into a notochord-like population. We expect that barRNA-seq willhave broad utility for investigating and understanding how cooperative signaling pathwaysdrive cell fate acquisition.

DOI: 10.1016/j.stem.2020.04.020

Source: https://www.cell.com/cell-stem-cell/fulltext/S1934-5909(20)30159-4

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