A Single-Cell Roadmap of Lineage Bifurcation in Human ESC Models of Embryonic Brain Development

作者：Yao Zizhen; Mich John K; Ku Sherman; Menon Vilas; Krostag Anne Rachel; Martinez Refugio A; Furchtgott Leon; Mulholland Heather; Bort Susan; Fuqua Margaret A; Gregor Ben W; Hodge Rebecca D; Jayabalu Anu; May Ryan C; Melton Samuel; Nelson Angelique M; Ngo N Kiet; Shapovalova Nadiya V; Shehata Soraya I; Smith Michael W; Tait Leah J; Thompson Carol L; Thomsen Elliot R; Ye Chaoyang; Glass Ian A; Kaykas Ajamete; Yao Shuyuan; Phillips John W

来源：Cell Stem Cell, 2017, 20(1): 120-134.

DOI：10.1016/j.stem.2016.09.011

During human brain development, multiple signaling pathways generate diverse cell types with varied regional identities. Here, we integrate single-cell RNA sequencing and clonal analyses to reveal lineage trees and molecular signals underlying early forebrain and mid/hindbrain cell differentiation from human embryonic stem cells (hESCs). Clustering single-cell transcriptomic data identified 41 distinct populations of progenitor, neuronal, and non-neural cells across our differentiation time course. Comparisons with primary mouse and human gene expression data demonstrated rostral and caudal progenitor and neuronal identities from early brain development. Bayesian analyses inferred a unified cell-type lineage tree that bifurcates between cortical and mid/hindbrain cell types. Two methods of clonal analyses confirmed these findings and further revealed the importance of Wnt/beta-catenin signaling in controlling this lineage decision. Together, these findings provide a rich transcriptome- based lineage map for studying human brain development and modeling developmental disorders.

• 出版日期2017-1-5