Abstract
The development of the human neocortex is highly dynamic, involving complex cellular trajectories controlled by gene regulation(1). Here we collected paired single-nucleus chromatin accessibility and transcriptome data from 38 human neocortical samples encompassing both the prefrontal cortex and the primary visual cortex. These samples span five main developmental stages, ranging from the first trimester to adolescence. In parallel, we performed spatial transcriptomic analysis on a subset of the samples to illustrate spatial organization and intercellular communication. This atlas enables us to catalogue cell-type-specific, age-specific and area-specific gene regulatory networks underlying neural differentiation. Moreover, combining single-cell profiling, progenitor purification and lineage-tracing experiments, we have untangled the complex lineage relationships among progenitor subtypes during the neurogenesis-to-gliogenesis transition. We identified a tripotential intermediate progenitor subtype-tripotential intermediate progenitor cells (Tri-IPCs)-that is responsible for the local production of GABAergic neurons, oligodendrocyte precursor cells and astrocytes. Notably, most glioblastoma cells resemble Tri-IPCs at the transcriptomic level, suggesting that cancer cells hijack developmental processes to enhance growth and heterogeneity. Furthermore, by integrating our atlas data with large-scale genome-wide association study data, we created a disease-risk map highlighting enriched risk associated with autism spectrum disorder in second-trimester intratelencephalic neurons. Our study sheds light on the molecular and cellular dynamics of the developing human neocortex.
PubMed ID: 39779846
Li Wang, PhD
Postdoctoral Scholar
Juan Moriano, PhD
Postdoctoral Scholar
Songcang Chen, MD
Senior Scientist
Guolong Zuo, PhD
Postdoctoral Scholar
Tanzila Mukhtar, PhD
Postdoctoral Scholar
Shaohui Wang
Specialist
Mengyi Song, PhD
Postdoctoral Scholar
Lilian Gomes de Oliveira, PhD
Postdoctoral Scholar
Quili Bi
Specialist
Jonathan Augustin, PhD
Postdoctoral Scholar
