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

By Gioele La Manno, Daniel Gyllborg, Simone Codeluppi, Kaneyasu Nishimura, C. Saltó, Amit Zeisel, Lars E. Borm, S. Stott, E. Toledo, J. C. Villaescusa and 5 more. Cell, 2016

796 citations recorded by the source corpus.

Summary 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.

Subfields: Genetics, Molecular Biology, Pediatrics, Perinatology and Child Health

View Paper: https://www.semanticscholar.org/paper/80da6e177a51b762fbb474b9820a13bbcadd00d3

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In Genetics

1. Amos Tanay
2. Alexander van Oudenaarden
3. Ivo G. Gut

In Molecular Biology

1. J. Lee
2. Duhee Bang
3. Byungjin Hwang
4. Hadas Keren-Shaul
5. Eyal David
6. Ido Amit
7. Amos Tanay
8. Holger Heyn

Citations in the corpus

• Comprehensive analysis of retinal development at single cell resolution identifies NFI factors as essential for mitotic exit and specification of late-born cells (2018, background): “…regions such as cerebral cortex and midbrain have analyzed only a few thousand cells, usually at a relatively smaller number of developmental ages (La Manno et al., 2016; Mayer et al., 2018; Nowakowski et al., 2017; Zhong et al., 2018), and thus do not fully capture the transcriptional changes…”
• bigSCale: an analytical framework for big-scale single-cell data (2017, result): “Among the most extensive data sets to date for scRNA-seq are 1,306,127 sequenced mouse brain cells from the developmental (E18) dorsal and medial pallium.”
• A Unique Microglia Type Associated with Restricting Development of Alzheimer's Disease. (2017, neutral): “…resolve immune heterogeneity in AD (Deng et al., 2014; Grün et al., 2015; Gury-BenAri et al., 2016; Jaitin et al., 2014; Junker and van Oudenaarden, 2014; La Manno et al., 2016; Mass et al., 2016; Matcovitch-Natan et al., 2016; Paul et al., 2015; Treutlein et al., 2014; Zeisel et al., 2015).”
• Single-cell RNA sequencing technologies and bioinformatics pipelines (2018, background): “Several emerging scRNA-seq studies have focused on deepening our understanding of cells in the brain 102,103 .”
• Dissecting Immune Circuits by Linking CRISPR-Pooled Screens with Single-Cell RNA-Seq. (2016, positive): “…types in various tissues and disease states (Gru¨n et al., 2015; Gury-BenAri et al., 2016; Jaitin et al., 2014; Junker and van Oudenaarden, 2014; La Manno et al., 2016; Paul et al., 2015; Segerstolpe et al., 2016; Shalek et al., 2014; Stegle et al., 2015; Treutlein et al., 2014; Zei-sel et al.,…”