Cell Reports (May 2020)
Variation of Human Neural Stem Cells Generating Organizer States In Vitro before Committing to Cortical Excitatory or Inhibitory Neuronal Fates
- Nicola Micali,
- Suel-Kee Kim,
- Marcelo Diaz-Bustamante,
- Genevieve Stein-O’Brien,
- Seungmae Seo,
- Joo-Heon Shin,
- Brian G. Rash,
- Shaojie Ma,
- Yanhong Wang,
- Nicolas A. Olivares,
- Jon I. Arellano,
- Kristen R. Maynard,
- Elana J. Fertig,
- Alan J. Cross,
- Roland W. Bürli,
- Nicholas J. Brandon,
- Daniel R. Weinberger,
- Joshua G. Chenoweth,
- Daniel J. Hoeppner,
- Nenad Sestan,
- Pasko Rakic,
- Carlo Colantuoni,
- Ronald D. McKay
Affiliations
- Nicola Micali
- Lieber Institute for Brain Development, 855 North Wolfe St., Baltimore, MD 21205, USA; Department of Neuroscience, Yale School of Medicine, New Haven, CT 06520, USA; Corresponding author
- Suel-Kee Kim
- Lieber Institute for Brain Development, 855 North Wolfe St., Baltimore, MD 21205, USA; Department of Neuroscience, Yale School of Medicine, New Haven, CT 06520, USA
- Marcelo Diaz-Bustamante
- Lieber Institute for Brain Development, 855 North Wolfe St., Baltimore, MD 21205, USA
- Genevieve Stein-O’Brien
- Lieber Institute for Brain Development, 855 North Wolfe St., Baltimore, MD 21205, USA; McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins School of Medicine, Baltimore, MD 21205, USA
- Seungmae Seo
- Lieber Institute for Brain Development, 855 North Wolfe St., Baltimore, MD 21205, USA
- Joo-Heon Shin
- Lieber Institute for Brain Development, 855 North Wolfe St., Baltimore, MD 21205, USA
- Brian G. Rash
- Department of Neuroscience, Yale School of Medicine, New Haven, CT 06520, USA
- Shaojie Ma
- Departments of Comparative Medicine, Genetics, and Psychiatry, Yale School of Medicine, New Haven, CT 06520, USA
- Yanhong Wang
- Lieber Institute for Brain Development, 855 North Wolfe St., Baltimore, MD 21205, USA
- Nicolas A. Olivares
- Lieber Institute for Brain Development, 855 North Wolfe St., Baltimore, MD 21205, USA
- Jon I. Arellano
- Department of Neuroscience, Yale School of Medicine, New Haven, CT 06520, USA
- Kristen R. Maynard
- Lieber Institute for Brain Development, 855 North Wolfe St., Baltimore, MD 21205, USA
- Elana J. Fertig
- Department of Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins School of Medicine, Baltimore, MD 21205, USA; Department of Biomedical Engineering, Johns Hopkins School of Medicine, Baltimore, MD 21205, USA; Department of Applied Mathematics and Statistics, Johns Hopkins School of Medicine, Baltimore, MD 21205, USA
- Alan J. Cross
- AstraZeneca Neuroscience, IMED Biotech Unit, R&D, Boston, MA 024515, USA
- Roland W. Bürli
- AstraZeneca Neuroscience, IMED Biotech Unit, R&D, Boston, MA 024515, USA
- Nicholas J. Brandon
- AstraZeneca Neuroscience, IMED Biotech Unit, R&D, Boston, MA 024515, USA
- Daniel R. Weinberger
- Lieber Institute for Brain Development, 855 North Wolfe St., Baltimore, MD 21205, USA; McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins School of Medicine, Baltimore, MD 21205, USA; Department of Neurology, Johns Hopkins School of Medicine, Baltimore, MD 21205, USA; Department of Psychiatry, Johns Hopkins School of Medicine, Baltimore, MD 21205, USA; Department of Neuroscience, Johns Hopkins School of Medicine, Baltimore, MD 21205, USA
- Joshua G. Chenoweth
- Lieber Institute for Brain Development, 855 North Wolfe St., Baltimore, MD 21205, USA
- Daniel J. Hoeppner
- Lieber Institute for Brain Development, 855 North Wolfe St., Baltimore, MD 21205, USA; Astellas Research Institute of America, 3565 General Atomics Ct., Ste. 200, San Diego, CA 92121, USA
- Nenad Sestan
- Department of Neuroscience, Yale School of Medicine, New Haven, CT 06520, USA; Departments of Comparative Medicine, Genetics, and Psychiatry, Yale School of Medicine, New Haven, CT 06520, USA; Kavli Institute for Neuroscience, Yale School of Medicine, New Haven, CT 06520, USA
- Pasko Rakic
- Department of Neuroscience, Yale School of Medicine, New Haven, CT 06520, USA; Kavli Institute for Neuroscience, Yale School of Medicine, New Haven, CT 06520, USA; Corresponding author
- Carlo Colantuoni
- Lieber Institute for Brain Development, 855 North Wolfe St., Baltimore, MD 21205, USA; Department of Neurology, Johns Hopkins School of Medicine, Baltimore, MD 21205, USA; Department of Neuroscience, Johns Hopkins School of Medicine, Baltimore, MD 21205, USA; Institute for Genome Sciences, University of Maryland School of Medicine, Baltimore, MD 21201, USA; Corresponding author
- Ronald D. McKay
- Lieber Institute for Brain Development, 855 North Wolfe St., Baltimore, MD 21205, USA; Corresponding author
- Journal volume & issue
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Vol. 31,
no. 5
Abstract
Summary: Better understanding of the progression of neural stem cells (NSCs) in the developing cerebral cortex is important for modeling neurogenesis and defining the pathogenesis of neuropsychiatric disorders. Here, we use RNA sequencing, cell imaging, and lineage tracing of mouse and human in vitro NSCs and monkey brain sections to model the generation of cortical neuronal fates. We show that conserved signaling mechanisms regulate the acute transition from proliferative NSCs to committed glutamatergic excitatory neurons. As human telencephalic NSCs develop from pluripotency in vitro, they transition through organizer states that spatially pattern the cortex before generating glutamatergic precursor fates. NSCs derived from multiple human pluripotent lines vary in these early patterning states, leading differentially to dorsal or ventral telencephalic fates. This work furthers systematic analyses of the earliest patterning events that generate the major neuronal trajectories of the human telencephalon.
