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

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作者
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
机构
[1] Icahn School of Medicine at Mount Sinai,Department of Pathology, Molecular, and Cell
[2] Icahn School of Medicine at Mount Sinai,Based Medicine
[3] Boston Children’s Hospital,Department of Neuroscience
[4] Icahn School of Medicine at Mount Sinai,Department of Neurology
[5] Icahn School of Medicine at Mount Sinai,Department of Genetics and Genomic Sciences
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Nature Communications | / 13卷
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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.
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