Single-cell reconstruction of developmental trajectories during zebrafish embryogenesis

被引:514
作者
Farrell, Jeffrey A. [1 ]
Wang, Yiqun [1 ]
Riesenfeld, Samantha J. [2 ]
Shekhar, Karthik [2 ]
Regev, Aviv [2 ,3 ]
Schier, Alexander F. [1 ,2 ,4 ,5 ,6 ,7 ]
机构
[1] Harvard Univ, Dept Mol & Cellular Biol, Cambridge, MA 02138 USA
[2] Broad Inst MIT & Harvard, Klarman Cell Observ, Cambridge, MA 02142 USA
[3] MIT, Howard Hughes Med Inst, Koch Inst Integrat Canc Res, Dept Biol, Cambridge, MA 02140 USA
[4] Harvard Univ, Ctr Brain Sci, Cambridge, MA 02138 USA
[5] Harvard Univ, FAS Ctr Syst Biol, Cambridge, MA 02138 USA
[6] Univ Basel, Biozentrum, Basel, Switzerland
[7] Univ Washington, Allen Discovery Ctr Cell Lineage Tracing, Seattle, WA 98195 USA
关键词
ENDODERM FORMATION; EXPRESSION; FATE; FIBROBLASTS; DYNAMICS; CASANOVA; PROTEIN; MAPS;
D O I
10.1126/science.aar3131
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
During embryogenesis, cells acquire distinct fates by transitioning through transcriptional states. To uncover these transcriptional trajectories during zebrafish embryogenesis, we sequenced 38,731 cells and developed URD, a simulated diffusion-based computational reconstruction method. URD identified the trajectories of 25 cell types through early somitogenesis, gene expression along them, and their spatial origin in the blastula. Analysis of Nodal signaling mutants revealed that their transcriptomes were canalized into a subset of wild-type transcriptional trajectories. Some wild-type developmental branch points contained cells that express genes characteristic of multiple fates. These cells appeared to trans-specify from one fate to another. These findings reconstruct the transcriptional trajectories of a vertebrate embryo, highlight the concurrent canalization and plasticity of embryonic specification, and provide a framework with which to reconstruct complex developmental trees from single-cell transcriptomes. 2017 © The Authors.
引用
收藏
页码:979 / +
页数:8
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