Citation

Yao Z, Mich JK, Ku S, Menon V, Krostag AR, Martinez RA, Furchtgott L, Mulholland H, Bort S, Fuqua MA, Gregor BW, Hodge RD, Jayabalu A, May RC, Melton S, Nelson AM, Ngo NK, Shapovalova NV, Shehata SI, Smith MW, Tait LJ, Thompson CL, Thomsen ER, Ye C, Glass IA, Kaykas A, Yao S, Phillips JW, Grimley JS, Levi BP, Wang Y, Ramanathan S. 2017. A Single-Cell Roadmap of Lineage Bifurcation in Human ESC Models of Embryonic Brain Development. Cell stem cell. 20(1):120-134. Pubmed: 28094016 DOI:10.1016/j.stem.2016.09.011

Abstract

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/β-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.
Copyright © 2017 Elsevier Inc. All rights reserved.

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Photo of Sharad Ramanathan

Sharad Ramanathan studies how the dynamics of the underlying circuits allow cells and organisms to make decisions. To do so he brings together Biology with tools from Applied Math, Microscopy and Microfluidics.

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