期刊
CELL
卷 167, 期 2, 页码 566-+出版社
CELL PRESS
DOI: 10.1016/j.cell.2016.09.027
关键词
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资金
- EU FP7 grant DDPDGENES
- European Research Council (BRAINCELL) [261063]
- Knut and Alice Wallenberg Foundation [2015.0041]
- Swedish Research Council (STARGET)
- Swedish Foundation for Strategic Research [RIF14-0057]
- Human Frontier Science Program
- Swedish Research Council (VR projects) [2011-3116, 2011-3318]
- Swedish Foundation for Strategic Research (SRL program)
- Karolinska Institutet (SFO Thematic Center in Stem cells and Regenerative Medicine)
- EU FP7 grant NeuroStem-cellRepair
- NIHR Biomedical Research Centre award
- European Research Council (ERC) [261063] Funding Source: European Research Council (ERC)
- Medical Research Council [MC_PC_12009] Funding Source: researchfish
- Swedish Foundation for Strategic Research (SSF) [RIF14-0057] Funding Source: Swedish Foundation for Strategic Research (SSF)
Understanding human embryonic ventral midbrain is of major interest for Parkinson's disease. However, the cell types, their gene expression dynamics, and their relationship to commonly used rodent models remain to be defined. We performed single-cell RNA sequencing to examine ventral midbrain development in human and mouse. We found 25 molecularly defined human cell types, including five subtypes of radial glia-like cells and four progenitors. In the mouse, two mature fetal dopaminergic neuron subtypes diversified into five adult classes during postnatal development. Cell types and gene expression were generally conserved across species, but with clear differences in cell proliferation, developmental timing, and dopaminergic neuron development. Additionally, we developed a method to quantitatively assess the fidelity of dopaminergic neurons derived from human pluripotent stem cells, at a single-cell level. Thus, our study provides insight into the molecular programs controlling human midbrain development and provides a foundation for the development of cell replacement therapies.
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