An atlas of late prenatal human neurodevelopment resolved by single-nucleus transcriptomics

Susana I. Ramos, Zarmeen M. Mussa, Elisa N. Falk, Balagopal Pai, Bruno Giotti, Kimaada Allette, Peiwen Cai, Fumiko Dekio, Robert Sebra, Kristin G. Beaumont, Alexander M. Tsankov, Nadejda M. Tsankova

Research output: Contribution to journalArticlepeer-review

7 Scopus citations

Abstract

Late prenatal development of the human neocortex encompasses a critical period of gliogenesis and cortical expansion. However, systematic single-cell analyses to resolve cellular diversity and gliogenic lineages of the third trimester are lacking. Here, we present a comprehensive single-nucleus RNA sequencing atlas of over 200,000 nuclei derived from the proliferative germinal matrix and laminating cortical plate of 15 prenatal, non-pathological postmortem samples from 17 to 41 gestational weeks, and 3 adult controls. This dataset captures prenatal gliogenesis with high temporal resolution and is provided as a resource for further interrogation. Our computational analysis resolves greater complexity of glial progenitors, including transient glial intermediate progenitor cell (gIPC) and nascent astrocyte populations in the third trimester of human gestation. We use lineage trajectory and RNA velocity inference to further characterize specific gIPC subpopulations preceding both oligodendrocyte (gIPC-O) and astrocyte (gIPC-A) lineage differentiation. We infer unique transcriptional drivers and biological pathways associated with each developmental state, validate gIPC-A and gIPC-O presence within the human germinal matrix and cortical plate in situ, and demonstrate gIPC states being recapitulated across adult and pediatric glioblastoma tumors.

Original languageEnglish
Article number7671
JournalNature Communications
Volume13
Issue number1
DOIs
StatePublished - Dec 2022

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