Single-cell analysis of prenatal and postnatal human cortical development.
Dmitry VelmeshevYonatan PerezZihan YanJonathan E ValenciaDavid R Castaneda-CastellanosLi WangLucas SchirmerSimone MayerBrittney WickShaohui WangTomasz Jan NowakowskiMercedes F ParedesEric J HuangArnold R KriegsteinPublished in: Science (New York, N.Y.) (2023)
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.
Keyphrases
- single cell
- rna seq
- gene expression
- transcription factor
- endothelial cells
- genome wide
- risk factors
- autism spectrum disorder
- high throughput
- preterm infants
- pregnant women
- public health
- dna methylation
- intellectual disability
- resting state
- white matter
- copy number
- induced pluripotent stem cells
- dna damage
- cell therapy
- oxidative stress
- pluripotent stem cells
- stem cells
- cell proliferation
- blood brain barrier
- electronic health record
- big data
- signaling pathway
- cell death
- single molecule
- cerebral ischemia
- binding protein