Single-cell lineage analysis reveals extensive multimodal transcriptional control during directed beta-cell differentiation.
Single-cell lineage analysis reveals extensive multimodal transcriptional control during directed beta-cell differentiation.
复制标题
单细胞谱系分析揭示了在定向β细胞分化过程中广泛的多模式转录控制。
DOI：
10.1038/s42255-020-00314-2
复制
发表时间：
2020-12
影响因子：
20.8
通讯作者：
Li Y
中科院分区：
文献类型：
--
作者：
Weng C;Xi J;Li H;Cui J;Gu A;Lai S;Leskov K;Ke L;Jin F;Li Y
The in vitro differentiation of insulin-producing β-like cells can model aspects of human pancreatic development. Here we generate 95,308 single cell transcriptomes and reconstruct a lineage tree of the entire differentiation process from hESCs to β-like cells to study temporally regulated genes during differentiation. We identify so-called ‘switch genes’ at the branch point of endocrine/non-endocrine cell fate choice, revealing insights into the mechanisms of differentiation promoting reagents, such as NOTCH and ROCKII inhibitors, and providing improved differentiation protocols. Over 20% of all detectable genes are activated multiple times during differentiation, even though their enhancer activation is usually unimodal, indicating extensive gene reuse driven by different enhancers. We also identify a stage-specific enhancer in the TCF7L2 diabetes GWAS locus that drives a transient wave of gene expression in pancreatic progenitors. Finally, we develop a web app to visualize gene expression on the lineage tree, providing a comprehensive single cell data resource for researchers studying islet biology and diabetes.
登录
查看更多内容
影响因子：
9.3
作者：
Baron M;Veres A;Wolock SL;Faust AL;Gaujoux R;Vetere A;Ryu JH;Wagner BK;Shen-Orr SS;Klein AM;Melton DA;Yanai I
通讯作者：
Yanai I
影响因子：
64.8
作者：
Cao, Junyue;Spielmann, Malte;Shendure, Jay
通讯作者：
Shendure, Jay
影响因子：
14.9
作者：
Buniello, Annalisa;MacArthur, Jacqueline A. L.;Parkinson, Helen
通讯作者：
Parkinson, Helen
影响因子：
64.8
作者：
Apelqvist, Å;Li, H;Edlund, H
通讯作者：
Edlund, H
影响因子：
8.8
作者：
Fang, Zhou;Weng, Chen;Li, Yan
通讯作者：
Li, Yan