Variation of Human Neural Stem Cells Generating Organizer States In Vitro before Committing to Cortical Excitatory or Inhibitory Neuronal Fates

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 vitr...

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Main Authors: 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
Format: Article
Language:English
Published: Elsevier 2020-05-01
Series:Cell Reports
Subjects:
Online Access:http://www.sciencedirect.com/science/article/pii/S2211124720305489
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author 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
author_facet 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
author_sort Nicola Micali
collection DOAJ
description 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.
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spelling doaj.art-09028c601a8b4575b9d6ec90dadc6fb02022-12-22T00:56:47ZengElsevierCell Reports2211-12472020-05-01315Variation of Human Neural Stem Cells Generating Organizer States In Vitro before Committing to Cortical Excitatory or Inhibitory Neuronal FatesNicola Micali0Suel-Kee Kim1Marcelo Diaz-Bustamante2Genevieve Stein-O’Brien3Seungmae Seo4Joo-Heon Shin5Brian G. Rash6Shaojie Ma7Yanhong Wang8Nicolas A. Olivares9Jon I. Arellano10Kristen R. Maynard11Elana J. Fertig12Alan J. Cross13Roland W. Bürli14Nicholas J. Brandon15Daniel R. Weinberger16Joshua G. Chenoweth17Daniel J. Hoeppner18Nenad Sestan19Pasko Rakic20Carlo Colantuoni21Ronald D. McKay22Lieber 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 authorLieber Institute for Brain Development, 855 North Wolfe St., Baltimore, MD 21205, USA; Department of Neuroscience, Yale School of Medicine, New Haven, CT 06520, USALieber Institute for Brain Development, 855 North Wolfe St., Baltimore, MD 21205, USALieber 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, USALieber Institute for Brain Development, 855 North Wolfe St., Baltimore, MD 21205, USALieber Institute for Brain Development, 855 North Wolfe St., Baltimore, MD 21205, USADepartment of Neuroscience, Yale School of Medicine, New Haven, CT 06520, USADepartments of Comparative Medicine, Genetics, and Psychiatry, Yale School of Medicine, New Haven, CT 06520, USALieber Institute for Brain Development, 855 North Wolfe St., Baltimore, MD 21205, USALieber Institute for Brain Development, 855 North Wolfe St., Baltimore, MD 21205, USADepartment of Neuroscience, Yale School of Medicine, New Haven, CT 06520, USALieber Institute for Brain Development, 855 North Wolfe St., Baltimore, MD 21205, USADepartment 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, USAAstraZeneca Neuroscience, IMED Biotech Unit, R&D, Boston, MA 024515, USAAstraZeneca Neuroscience, IMED Biotech Unit, R&D, Boston, MA 024515, USAAstraZeneca Neuroscience, IMED Biotech Unit, R&D, Boston, MA 024515, USALieber 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, USALieber Institute for Brain Development, 855 North Wolfe St., Baltimore, MD 21205, USALieber 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, USADepartment 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, USADepartment 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 authorLieber 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 authorLieber Institute for Brain Development, 855 North Wolfe St., Baltimore, MD 21205, USA; Corresponding authorSummary: 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.http://www.sciencedirect.com/science/article/pii/S2211124720305489neural stem cellFGF2BMPneural transcriptional dynamicsneurogenesisEGFR
spellingShingle 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
Variation of Human Neural Stem Cells Generating Organizer States In Vitro before Committing to Cortical Excitatory or Inhibitory Neuronal Fates
Cell Reports
neural stem cell
FGF2
BMP
neural transcriptional dynamics
neurogenesis
EGFR
title Variation of Human Neural Stem Cells Generating Organizer States In Vitro before Committing to Cortical Excitatory or Inhibitory Neuronal Fates
title_full Variation of Human Neural Stem Cells Generating Organizer States In Vitro before Committing to Cortical Excitatory or Inhibitory Neuronal Fates
title_fullStr Variation of Human Neural Stem Cells Generating Organizer States In Vitro before Committing to Cortical Excitatory or Inhibitory Neuronal Fates
title_full_unstemmed Variation of Human Neural Stem Cells Generating Organizer States In Vitro before Committing to Cortical Excitatory or Inhibitory Neuronal Fates
title_short Variation of Human Neural Stem Cells Generating Organizer States In Vitro before Committing to Cortical Excitatory or Inhibitory Neuronal Fates
title_sort variation of human neural stem cells generating organizer states in vitro before committing to cortical excitatory or inhibitory neuronal fates
topic neural stem cell
FGF2
BMP
neural transcriptional dynamics
neurogenesis
EGFR
url http://www.sciencedirect.com/science/article/pii/S2211124720305489
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