Molecular and cellular dynamics of the developing human neocortex at single-cell resolution
Data files
Aug 20, 2024 version files 135.22 GB
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GPC_differentiation_scRNA-seq_filtered_feature_bc_matrix.h5
393.19 MB
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GPC_differentiation_scRNA-seq_Seurat_object.rds
19.18 GB
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MERFISH_Seurat__object.rds
3.42 GB
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README.md
3.41 KB
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snMultiome_atlas_atac_fragments.tsv.zip
70.70 GB
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snMultiome_atlas_filtered_feature_bc_matrix.h5.zip
3.42 GB
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snMultiome_atlas_Seurat_object.rds
32.80 GB
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SSTR_agonist_treatment_scRNA-seq_EN_Seurat_object.rds
5.31 GB
Abstract
The development of the human neocortex is a highly dynamic process and involves complex cellular trajectories controlled by cell-type-specific gene regulation. Here, we collected paired single-nucleus chromatin accessibility and transcriptome data from 38 human neocortical samples encompassing both the prefrontal cortex and 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 catalog cell type-, age-, 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 transition from neurogenesis to gliogenesis in the human neocortex. We identified a tripotential intermediate progenitor subtype, termed Tri-IPC, responsible for the local production of GABAergic neurons, oligodendrocyte precursor cells, and astrocytes. Remarkably, 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 GWAS data, we created a disease-risk map highlighting enriched ASD risk in second-trimester intratelencephalic projection neurons. Our study sheds light on the gene regulatory landscape and cellular dynamics of the developing human neocortex.
README: Molecular and cellular dynamics of the developing human neocortex at single-cell resolution
https://doi.org/10.5061/dryad.2280gb612
We collected paired single-nucleus chromatin accessibility and transcriptome data (10x Multiome) from the developing human neocortex.
We collected MERFISH data (Vizgen MERSCOPE) from the developing human neocortex.
We collected scRNA-seq data (10x Flex) from cultured slices treated with and without somatostatin receptor (SSTR) agonists.
We collected scRNA-seq data (10x 3' v3.1) from FACS-isolated glial progenitor cells (GPCs) during in vitro differentiation.
Description of the data and file structure
For 10x Multiome data:
- The 10x Genomics Cellranger ARC output files, including atac_fragments.tsv.gz and atac_fragments.tsv.gz.tbi, and filtered_feature_bc_matrix.h5 for each sample (38 samples in total). We used GRCh38 Reference - 2020-A-2.0.0 as the reference file. Detailed information and format of these files can be found here and here. Additional information on these samples can be found in the Supplementary Table 1 of our publication.
- A Seurat object containing count matrices, dimension reduction, and metadata from 38 samples in this experiment (snMultiome_atlas_Seurat_object.rds).
For MERFISH data (Vizgen MERSCOPE): A Seurat object containing spatial coordinates, count matrices, dimension reduction, and metadata from six samples in this experiment (MERFISH_Seurat__object.rds).
For SSTR agonist treatment data (10x Flex): A Seurat object containing count matrices, dimension reduction, and metadata of excitatory neurons from 20 samples in this experiment (SSTR_agonist_treatment_scRNA-seq_EN_Seurat_object.rds).
For GPC differentiation data (10x 3' v3.1):
- The 10x Genomics Cellranger output (GPC_differentiation_scRNA-seq_filtered_feature_bc_matrix.h5). We used GRCh38 Reference - 2020-A-2.0.0 as the reference file. Detailed information and format of these files can be found here.
- A Seurat object containing count matrices, dimension reduction, and metadata from 9 samples in this experiment (GPC_differentiation_scRNA-seq_Seurat_object.rds).
Sharing/Access information
Links to raw fastq files for snMultiome:
Links to original Vizgen output files for MERFISH:
Links to interactive data browsers:
- https://cell.ucsf.edu/snMultiome
- https://cellxgene.cziscience.com/collections/ad2149fc-19c5-41de-8cfe-44710fbada73
Publication
If using these data, please consider citing our publication Molecular and cellular dynamics of the developing human neocortex at single-cell resolution.