Molecular Diversity of Midbrain Development in Mouse, Human, and Stem Cells.

Abstract:

: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.

journal_name

Cell

journal_title

Cell

authors

La Manno G,Gyllborg D,Codeluppi S,Nishimura K,Salto C,Zeisel A,Borm LE,Stott SRW,Toledo EM,Villaescusa JC,Lönnerberg P,Ryge J,Barker RA,Arenas E,Linnarsson S

doi

10.1016/j.cell.2016.09.027

subject

Has Abstract

pub_date

2016-10-06 00:00:00

pages

566-580.e19

issue

2

eissn

0092-8674

issn

1097-4172

pii

S0092-8674(16)31309-5

journal_volume

167

pub_type

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