| Literature DB >> 28094016 |
Zizhen Yao1, John K Mich1, Sherman Ku1, Vilas Menon1, Anne-Rachel Krostag1, Refugio A Martinez1, Leon Furchtgott2, Heather Mulholland1, Susan Bort1, Margaret A Fuqua1, Ben W Gregor1, Rebecca D Hodge1, Anu Jayabalu1, Ryan C May1, Samuel Melton3, Angelique M Nelson1, N Kiet Ngo1, Nadiya V Shapovalova1, Soraya I Shehata1, Michael W Smith1, Leah J Tait1, Carol L Thompson1, Elliot R Thomsen1, Chaoyang Ye1, Ian A Glass4, Ajamete Kaykas1, Shuyuan Yao1, John W Phillips1, Joshua S Grimley5, Boaz P Levi6, Yanling Wang7, Sharad Ramanathan8.
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.Entities:
Keywords: human embryonic stem cells; lineage; neurogenesis; single cell RNA-seq
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Year: 2016 PMID： 28094016 PMCID： PMC5261831 DOI： 10.1016/j.stem.2016.09.011
Source DB: PubMed Journal: Cell Stem Cell ISSN： 1875-9777 Impact factor: 24.633