Single-cell analysis of prenatal and postnatal human cortical development
Dmitry Velmeshev, Yonatan Perez, Zihan Yan, Jonathan E. Valencia, David R. Castaneda-Castellanos, Li Wang, Lucas Schirmer, Simone Mayer, Brittney Wick, Shaohui Wang, Tomasz Jan Nowakowski, Mercedes Paredes, Eric J. Huang, Arnold R. Kriegstein
Abstract
We analyzed >700,000 single-nucleus RNA sequencing profiles from 106 donors during prenatal and postnatal developmental stages and identified lineage-specific programs that underlie the development of specific subtypes of excitatory cortical neurons, interneurons, glial cell types, and brain vasculature. By leveraging single-nucleus chromatin accessibility data, we delineated enhancer gene regulatory networks and transcription factors that control commitment of specific cortical lineages. By intersecting our results with genetic risk factors for human brain diseases, we identified the cortical cell types and lineages most vulnerable to genetic insults of different brain disorders, especially autism. We find that lineage-specific gene expression programs up-regulated in female cells are especially enriched for the genetic risk factors of autism. Our study captures the molecular progression of cortical lineages across human development.
Datasets
1. Single-cell analysis of prenatal and postnatal human cortical development
Metadata
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NCBITaxon:9606709372 cells UBERON:0001870457164 cells UBERON:000302775807 cells UBERON:001653866902 cells UBERON:000095648237 cells UBERON:003489134153 cells HsapDv:0000199265118 cells HsapDv:000020248889 cells HsapDv:000020334292 cells HsapDv:000020130112 cells HsapDv:000019829589 cells HsapDv:000020025845 cells HsapDv:000024625137 cells HsapDv:000009622476 cells HsapDv:000017419291 cells HsapDv:000010014490 cells HsapDv:000010613261 cells HsapDv:000011412915 cells HsapDv:000025612842 cells HsapDv:000017610388 cells HsapDv:000010710370 cells HsapDv:000017810272 cells Frontoparietal cortex178580 cells Primary motor cortex8400 cells oligodendrocyte40875 cells oligodendrocyte precursor cell31392 cells microglial cell15957 cells frontal cortex457164 cells cingulate cortex75807 cells temporal cortex66902 cells cerebral cortex48237 cells insular cortex34153 cells primary motor cortex8400 cells lateral ganglionic eminence6448 cells caudal ganglionic eminence4698 cells ganglionic eminence4126 cells medial ganglionic eminence3437 cells fifth LMP month human stage265118 cells eighth LMP month human stage48889 cells ninth LMP month human stage34292 cells seventh LMP month human stage30112 cells fourth LMP month human stage29589 cells sixth LMP month human stage25845 cells 1-year-old human stage25137 cells 2-year-old human stage22476 cells 1-month-old human stage19291 cells 6-year-old human stage14490 cells 12-year-old human stage13261 cells 20-year-old human stage12915 cells under-1-year-old human stage12842 cells 3-month-old human stage10388 cells 13-year-old human stage10370 cells 5-month-old human stage10272 cells 4-year-old human stage9863 cells 15-year-old human stage9584 cells newborn human stage9369 cells 19-year-old human stage8930 cells 16-year-old human stage7243 cells 3-year-old human stage6897 cells 8-year-old human stage6557 cells 2-month-old human stage6540 cells 17-year-old human stage6430 cells 14-year-old human stage6187 cells 40-year-old human stage5894 cells 25-year-old human stage5781 cells 22-year-old human stage4802 cells 10-year-old human stage4454 cells 4-month-old human stage4277 cells 21-year-old human stage3607 cells 28-year-old human stage3213 cells 5-year-old human stage2726 cells 45-year-old human stage2624 cells 53-year-old human stage2563 cells 34-year-old human stage2084 cells 44-year-old human stage1947 cells 39-year-old human stage1547 cells 54-year-old human stage966 cells Analyze this study
Source data
https://cellxgene.cziscience.com/collections/bacccb91-066d-4453-b70e-59de0b4598cd
Alias names
PMID37824647, PMC11005279
Cite this study
Velmeshev, D., Perez, Y., Yan, Z., Valencia, J.E., Castaneda-Castellanos, D.R., Wang, L., Schirmer, L., Mayer, S., Wick, B., Wang, S. and Nowakowski, T.J., 2023. Single-cell analysis of prenatal and postnatal human cortical development. Science, 382(6667), p.eadf0834. https://doi.org/10.1126/science.adf0834
