Human cortical neural stem cells generate regional organizer states in vitro before committing to excitatory neuronal fates

Nicola Micali, Suel Kee Kim, Marcelo Diaz-Bustamante, Genevieve Stein-O’Brien, Seungmae Seo, Joo Heon Shin, Brian G. Rash, Shaojie Ma, Nicolas A. Olivares, Jon Arellano, Kristen R. Maynard, Elana J. Fertig, Alan J. Cross, Roland Burli, Nicholas J. Brandon, Daniel R. Weinberger, Joshua G. Chenoweth, Daniel J. Hoeppner, Nenad Sestan, Pasko RakicCarlo Colantuoni, Ronald D. McKay

Research output: Contribution to journalArticlepeer-review

Abstract

Better understanding of the mechanisms underlying the developmental progression of neural stem cells (NSCs) in the cerebral cortex is important for modeling neurogenesis and defining the pathogenesis of neuropsychiatric disorders. Here we used RNA-sequencing, cell imaging and lineage tracing of mouse, macaque and human neurogenesis, along with single-cell RNA-sequencing and immuno-labeling to explore how cortical glutamatergic excitatory neurons are generated in vitro and in vivo. This analysis revealed that conserved signaling mechanisms regulate glutamatergic neurogenesis among the three species. We then show that as human telencephalic NSCs develop in vitro, they first generate the organizer states that spatially pattern the cortex before progressing to excitatory neuronal fates. This developmental progression of human NSCs in vitro opens to systematic analysis key aspects of human-specific area patterning during cortical neurogenesis.

Original languageEnglish (US)
JournalUnknown Journal
DOIs
StatePublished - Mar 15 2019

Keywords

  • BMP
  • cortical evolution
  • corticogenesis
  • EGFR
  • FGF2
  • human neurogenesis
  • Neural stem cells
  • neuronal differentiation
  • patterning of the cortex
  • transcriptional dynamics

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • Immunology and Microbiology(all)
  • Neuroscience(all)
  • Pharmacology, Toxicology and Pharmaceutics(all)

Fingerprint Dive into the research topics of 'Human cortical neural stem cells generate regional organizer states in vitro before committing to excitatory neuronal fates'. Together they form a unique fingerprint.

Cite this