Human intermediate progenitor diversity during cortical development. Pebworth, M., Ross, J., Andrews, M., Bhaduri, A., & Kriegstein, A. R Proc Natl Acad Sci U S A, June, 2021.
abstract   bibtex   
Studies of the spatiotemporal, transcriptomic, and morphological diversity of radial glia (RG) have spurred our current models of human corticogenesis. In the developing cortex, neural intermediate progenitor cells (nIPCs) are a neuron-producing transit-amplifying cell type born in the germinal zones of the cortex from RG. The potential diversity of the nIPC population, that produces a significant portion of excitatory cortical neurons, is understudied, particularly in the developing human brain. Here we explore the spatiotemporal, transcriptomic, and morphological variation that exists within the human nIPC population and provide a resource for future studies. We observe that the spatial distribution of nIPCs in the cortex changes abruptly around gestational week (GW) 19/20, marking a distinct shift in cellular distribution and organization during late neurogenesis. We also identify five transcriptomic subtypes, one of which appears at this spatiotemporal transition. Finally, we observe a diversity of nIPC morphologies that do not correlate with specific transcriptomic subtypes. These results provide an analysis of the spatiotemporal, transcriptional, and morphological diversity of nIPCs in developing brain tissue and provide an atlas of nIPC subtypes in the developing human cortex that can benchmark in vitro models of human development such as cerebral organoids and help inform future studies of how nIPCs contribute to cortical neurogenesis.
@ARTICLE{Pebworth2021-nn,
  title    = "Human intermediate progenitor diversity during cortical
              development",
  author   = "Pebworth, Mark-Phillip and Ross, Jayden and Andrews, Madeline and
              Bhaduri, Aparna and Kriegstein, Arnold R",
  abstract = "Studies of the spatiotemporal, transcriptomic, and morphological
              diversity of radial glia (RG) have spurred our current models of
              human corticogenesis. In the developing cortex, neural
              intermediate progenitor cells (nIPCs) are a neuron-producing
              transit-amplifying cell type born in the germinal zones of the
              cortex from RG. The potential diversity of the nIPC population,
              that produces a significant portion of excitatory cortical
              neurons, is understudied, particularly in the developing human
              brain. Here we explore the spatiotemporal, transcriptomic, and
              morphological variation that exists within the human nIPC
              population and provide a resource for future studies. We observe
              that the spatial distribution of nIPCs in the cortex changes
              abruptly around gestational week (GW) 19/20, marking a distinct
              shift in cellular distribution and organization during late
              neurogenesis. We also identify five transcriptomic subtypes, one
              of which appears at this spatiotemporal transition. Finally, we
              observe a diversity of nIPC morphologies that do not correlate
              with specific transcriptomic subtypes. These results provide an
              analysis of the spatiotemporal, transcriptional, and
              morphological diversity of nIPCs in developing brain tissue and
              provide an atlas of nIPC subtypes in the developing human cortex
              that can benchmark in vitro models of human development such as
              cerebral organoids and help inform future studies of how nIPCs
              contribute to cortical neurogenesis.",
  journal  = "Proc Natl Acad Sci U S A",
  volume   =  118,
  number   =  26,
  month    =  jun,
  year     =  2021,
  keywords = "cortex; development; human; neuronal; progenitor",
  language = "en"
}

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