Molecular and cellular dynamics of the developing human neocortex
Cite
Wang, L., Wang, C., Moriano, J.A., Chen, S., Zuo, G., Cebrián-Silla, A., Zhang, S., Mukhtar, T., Wang, S., Song, M. and de Oliveira, L.G., 2025. Molecular and cellular dynamics of the developing human neocortex. Nature, pp.1-10. https://doi.org/10.1038/s41586-024-08351-7
Abstract
The development of the human neocortex is highly dynamic, involving complex cellular trajectories controlled by gene regulation1. 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.
Datasets
1. snMultiome data of the developing human neocortex
ExploreLibrary ID
Sample ID
Age group
Brain region
Cell type (class)
Cell type (Subclass)
Cell type
Cell type (updated)
Subject ID
Assay
Disease
Sex
Tissue
Ethnicity
Age
Age (estimated day)
Clustering
Sample preservation method
Reference genome
NIH-4267-BA10-210,426 cells HDBR-14831-CTX10,180 cells ARKFrozen-43-PFC9,874 cells ARKFrozen-41-PFC-28,443 cells NIH-1325-BA10-28,136 cells ARKFrozen-19-V17,220 cells NIH-4373-BA9-36,698 cells NIH-1671-BA10-26,650 cells ARKFrozen-41-V16,324 cells ARKFrozen-18-PFC6,132 cells ARKFrozen-20-CTX6,088 cells HDBR-14584-CTX5,619 cells NIH-M2837-BA10-25,569 cells ARKFrozen-32-V15,520 cells ARKFrozen-1-PFC5,266 cells ARKFrozen-37-CTX4,947 cells ARKFrozen-8-V14,911 cells ARKFrozen-45-CTX4,814 cells NIH-M1154-BA10-24,367 cells NIH-4458-BA9-32,741 cells GW27-2-7-18-PFC2,027 cells NIH-4267-BA10-210,426 cells HDBR-14831-CTX10,180 cells ARKFrozen-43-PFC9,874 cells ARKFrozen-41-PFC-28,443 cells NIH-1325-BA10-28,136 cells ARKFrozen-19-V17,220 cells NIH-4373-BA9-36,698 cells NIH-1671-BA10-26,650 cells ARKFrozen-41-V16,324 cells ARKFrozen-18-PFC6,132 cells ARKFrozen-20-CTX6,088 cells HDBR-14584-CTX5,619 cells NIH-M2837-BA10-25,569 cells ARKFrozen-32-V15,520 cells ARKFrozen-1-PFC5,266 cells ARKFrozen-37-CTX4,947 cells ARKFrozen-8-V14,911 cells ARKFrozen-45-CTX4,814 cells NIH-M1154-BA10-24,367 cells NIH-4458-BA9-32,741 cells GW27-2-7-18-PFC2,027 cells Second_trimester69,539 cells Third_trimester24,716 cells First_trimester23,857 cells Glutamatergic neuron109,285 cells GABAergic neuron35,864 cells Oligodendrocyte24,613 cells Cajal-Retzius cell865 cells Oligodendrocyte23,357 cells EN-IT-Immature14,400 cells EN-Non-IT-Immature9,868 cells Astrocyte-Immature4,741 cells Astrocyte-Fibrous4,265 cells IN-MGE-Immature4,213 cells Astrocyte-Protoplasmic2,979 cells IN-CGE-Immature2,816 cells IN-dLGE-Immature2,597 cells Oligodendrocyte-Immature1,256 cells Cajal-Retzius cell865 cells Oligodendrocyte23,357 cells EN-IT-Immature14,400 cells EN-Non-IT-Immature9,868 cells Astrocyte-Immature4,741 cells Astrocyte-Fibrous4,265 cells IN-MGE-Immature4,213 cells Astrocyte-Protoplasmic2,979 cells IN-CGE-Immature2,816 cells IN-NCx_dGE-Immature2,597 cells Oligodendrocyte-Immature1,256 cells Cajal-Retzius cell865 cells 10x multiome232,328 cells Brodmann (1909) area 1756,895 cells Brodmann (1909) area 1042,837 cells Brodmann (1909) area 937,173 cells prefrontal cortex31,742 cells visual cortex23,975 cells African American58,491 cells Carnegie stage 2310,476 cells Carnegie stage 213,201 cells GRCh38, GENCODE v32/Ensembl98232,328 cells 2. scRNA-seq data of SSTR agonist treatment
ExploreSample ID
Subject ID
Age
Date
Treatment
Replication
Cell type (SCN - thresh0)
Cell type (SCN - thresh0.1)
Cell type (SCN - thresh0.15)
Cell type (SCN - thresh0.2)
Cell type (SCN - thresh0.3)
Cell type (class)
Cell type (subclass)
Cell type
Tissue
Tissue type
Disease
Assay
Reference genome
SCT clustering (snn_res.3)
SCT clustering (snn_res.5)
SCT clustering (snn_res.2)
SCT clustering (snn_res.1.5)
SCT clustering (snn_res.1)
SCT clustering (snn_res.6)
SCT clustering (snn_res.2.5
Seurat clusters
GW16_0315_Control_16,306 cells GW18_0426_Ostreotide_15,407 cells GW19_0412_Control_14,952 cells GW19_0412_Ostreotide_14,809 cells GW19_0412_L-054264_14,658 cells GW19_0405_Control_14,490 cells GW16_0315_Ostreotide_14,348 cells GW16_0315_L-054264_14,346 cells GW18_0426_L-054264_13,969 cells GW17_0508_Control_13,941 cells GW24_0424_Control_13,908 cells GW17_0508_Ostreotide_13,901 cells GW19_0412_Control_23,845 cells GW18_0426_Control_13,764 cells GW17_0508_L-054264_13,633 cells GW19_0405_Ostreotide_13,631 cells GW24_0424_L-054264_13,453 cells GW19_0405_L-054264_13,411 cells GW24_0424_Ostreotide_13,285 cells GW24_0424_Control_23,003 cells EN-IT-Immature5,668 cells EN-Non-IT-Immature2,191 cells Oligodendrocyte-Immature2 cells Cajal-Retzius cell2 cells EN-IT-Immature5,667 cells EN-Non-IT-Immature2,175 cells Cajal-Retzius cell2 cells Oligodendrocyte-Immature1 cells EN-IT-Immature5,356 cells EN-Non-IT-Immature1,840 cells EN-IT-Immature3,485 cells EN-Non-IT-Immature999 cells EN-Non-IT-Immature92 cells Glutamatergic neuron83,060 cells EN-IT-Immature15,123 cells EN-Non-IT-Immature1,373 cells 10x Chromium 3’83,060 cells 3. MERFISH data of developing neocortex
ExploreSample ID
Age group
Brain region
Brain region (detail)
Cell type (class)
Cell type (subclass)
Cell type
Tissue annotation
Cell type (updated)
Leiden clustering
Age (estimated days)
Clustering (integrated snn_res.2.8)
Seurat clusters
Subject ID
Tissue
Disease
Assay
ARKFrozen-65-V1169,905 cells NIH-5900-BA1756,343 cells NIH-4365-BA1052,483 cells ARKFrozen-62-PFC51,074 cells UCSF2018-003-MFG47,632 cells NIH-4392-BA1726,593 cells Second_trimester220,979 cells Third_trimester108,826 cells Middle frontal gyrus47,632 cells Glutamatergic neuron221,637 cells GABAergic neuron77,896 cells Oligodendrocyte4,797 cells EN-IT-Immature45,304 cells IN-MGE-Immature21,681 cells IN-CGE-Immature21,663 cells Astrocyte-Protoplasmic15,959 cells Astrocyte-Fibrous15,286 cells IN-dLGE-Immature3,937 cells Oligodendrocyte-Immature2,981 cells Oligodendrocyte1,816 cells Intermediate zone66,925 cells Cortical layer 6 and subplate64,051 cells Ventricular zone and subventricular zone54,561 cells Cortical layer 2 and 344,864 cells White matter and Meninge43,781 cells Cortical layer 540,894 cells Cortical layer 433,812 cells Cortical upper layer in development32,493 cells Dorsal lateral ganglionic eminence11,774 cells Cortical layer 110,875 cells EN-IT-Immature45,304 cells IN-MGE-Immature21,681 cells IN-CGE-Immature21,663 cells Astrocyte-Protoplasmic15,959 cells Astrocyte-Fibrous15,286 cells IN-NCx_dGE-Immature3,937 cells Oligodendrocyte-Immature2,981 cells Oligodendrocyte1,816 cells Brain cortex404,030 cells Alias names
Human developing brain scMultiome atlas
