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

La Manno, Gioele; Gyllborg, Daniel; Codeluppi, Simone; Nishimura, Kaneyasu; Salto, Carmen; Zeisel, Amit; Borm, Lars E; Stott, Simon R W LU ; Toledo, Enrique M and Villaescusa, J Carlos, et al. (2016) In Cell 167(2). p.566-580
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... (More)

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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publication status
published
subject
in
Cell
volume
167
issue
2
pages
566 - 580
publisher
Cell Press
external identifiers
  • scopus:84990876505
ISSN
0092-8674
DOI
10.1016/j.cell.2016.09.027
language
English
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no
id
e2d69cce-ced3-4048-bf03-cd496daacfff
date added to LUP
2016-11-23 13:03:34
date last changed
2017-10-22 05:22:20
@article{e2d69cce-ced3-4048-bf03-cd496daacfff,
  abstract     = {<p>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.</p>},
  articleno    = {e19},
  author       = {La Manno, Gioele and Gyllborg, Daniel and Codeluppi, Simone and Nishimura, Kaneyasu and Salto, Carmen and Zeisel, Amit and Borm, Lars E and Stott, Simon R W and Toledo, Enrique M and Villaescusa, J Carlos and Lönnerberg, Peter and Ryge, Jesper and Barker, Roger A and Arenas, Ernest and Linnarsson, Sten},
  issn         = {0092-8674},
  language     = {eng},
  month        = {10},
  number       = {2},
  pages        = {566--580},
  publisher    = {Cell Press},
  series       = {Cell},
  title        = {Molecular Diversity of Midbrain Development in Mouse, Human, and Stem Cells},
  url          = {http://dx.doi.org/10.1016/j.cell.2016.09.027},
  volume       = {167},
  year         = {2016},
}