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

doi:10.1126/science.adf0834

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

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42 Scopus citations

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.

Original language	English
Article number	adf0834
Journal	Science
Volume	382
Issue number	6667
DOIs	https://doi.org/10.1126/science.adf0834
State	Published - 13 Oct 2023
Externally published	Yes

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title = "Single-cell analysis of prenatal and postnatal human cortical development",

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.",

author = "Dmitry Velmeshev and Yonatan Perez and Zihan Yan and Valencia, {Jonathan E.} and Castaneda-Castellanos, {David R.} and Li Wang and Lucas Schirmer and Simone Mayer and Brittney Wick and Shaohui Wang and Nowakowski, {Tomasz Jan} and Mercedes Paredes and Huang, {Eric J.} and Kriegstein, {Arnold R.}",

year = "2023",

month = oct,

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doi = "10.1126/science.adf0834",

language = "English",

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T1 - Single-cell analysis of prenatal and postnatal human cortical development

AU - Velmeshev, Dmitry

AU - Perez, Yonatan

AU - Yan, Zihan

AU - Valencia, Jonathan E.

AU - Castaneda-Castellanos, David R.

AU - Wang, Li

AU - Schirmer, Lucas

AU - Mayer, Simone

AU - Wick, Brittney

AU - Wang, Shaohui

AU - Nowakowski, Tomasz Jan

AU - Paredes, Mercedes

AU - Huang, Eric J.

AU - Kriegstein, Arnold R.

PY - 2023/10/13

Y1 - 2023/10/13

N2 - 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.

AB - 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.

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VL - 382

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Single-cell analysis of prenatal and postnatal human cortical development

Abstract

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