A Single-Cell Roadmap of Lineage Bifurcation in Human ESC Models of Embryonic Brain Development
| Autor: | Ben W. Gregor, Anu Jayabalu, John W. Phillips, Nadiya V. Shapovalova, John K. Mich, Margaret A. Fuqua, Leah J. Tait, Carol L. Thompson, N. Kiet Ngo, Samuel Melton, Heather Mulholland, Shuyuan Yao, Joshua S. Grimley, Anne-Rachel F. Krostag, Sharad Ramanathan, Chaoyang Ye, Ajamete Kaykas, Vilas Menon, Angelique M. Nelson, Boaz P. Levi, Ian A. Glass, Sherman Ku, Elliot R. Thomsen, Yanling Wang, Rebecca D. Hodge, Soraya I. Shehata, Ryan C. May, Zizhen Yao, Leon Furchtgott, Refugio A. Martinez, Michael W. Smith, Susan Bort |
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| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Lineage (genetic) Cellular differentiation Human Embryonic Stem Cells Embryonic Development Hindbrain Biology Bioinformatics Models Biological Article Cell Line Transcriptome 03 medical and health sciences Mice 0302 clinical medicine Genetics Animals Humans Cell Lineage Wnt Signaling Pathway Neurons Sequence Analysis RNA Wnt signaling pathway Brain Reproducibility of Results Cell Biology Embryonic stem cell Clone Cells 030104 developmental biology Evolutionary biology Forebrain Molecular Medicine Single-Cell Analysis 030217 neurology & neurosurgery Stem cell lineage database Transcription Factors |
| Zdroj: | Cell stem cell. 20(1) |
| ISSN: | 1875-9777 |
| Popis: | 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 progenitors, 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. |
| Databáze: | OpenAIRE |
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