type: basic meta: summary: | Zemke et al, Conserved and divergent gene regulatory programs of the mammalian neocortex, Nature 2023 description: | The study presents a cross-species single-nucleus multiomic analysis of the primary motor cortex in human, macaque, marmoset, and mouse (M1 in the primate species and MOp in mouse). It examines how cell-type-specific molecular and regulatory features of the motor cortex are conserved or have diverged across mammalian evolution. By integrating several genomic modalities across corresponding cell subclasses, the study provides a comparative view of transcriptional regulation, chromatin state, DNA methylation, and 3D genome organization across the four species. The study uses two complementary assays. 10x Multiome jointly measures gene expression and chromatin accessibility, covering 157,424 nuclei, while snm3C-seq measures DNA methylation and 3D chromatin conformation, covering 24,283 nuclei. The 10x Multiome data come from 23 sample/library preparations distributed across the four species, and the cells are organized into 21 major subclasses spanning excitatory neurons, inhibitory neurons, and non-neuronal cell types. These matched subclasses form the basis for comparing molecular and regulatory features across species. [Zemke et al, Conserved and divergent gene regulatory programs of the mammalian neocortex, Nature 2023.](https://www.nature.com/articles/s41586-023-06819-6) 
            zemke2023Conserved/
            ├── atac_fragments/                      22 resources
            │   ├── 2C_rep1_deep
            │   ├── 2C_rep2_deep
            │   ├── 3C_rep1_deep
            │   └── ...
            ├── rna_expression_atac_matrix/          23 resources
            │   ├── M1_Dheni
            │   ├── M1_Dheni_neun
            │   ├── M1_donor1
            │   └── ...
            ├── rna_expression_matrix/                4 resources
            │   ├── human
            │   ├── macaque
            │   ├── marmoset
            │   └── mouse
            ├── pseudobulk_atac/                     80 resources
            │   ├── human_m1/                        20 resources
            │   │   ├── ASC
            │   │   ├── Endo
            │   │   ├── ...
            │   │   └── VLMC
            │   ├── macaque_m1/                      20 resources
            │   ├── marmoset_m1/                     20 resources
            │   └── mouse_mop/                       20 resources
            ├── pseudobulk_rna/                      80 resources
            │   ├── human_m1/                        20 resources
            │   │   ├── ASC
            │   │   ├── Endo
            │   │   ├── ...
            │   │   └── VLMC
            │   ├── macaque_m1/                      20 resources
            │   ├── marmoset_m1/                     20 resources
            │   └── mouse_mop/                       20 resources
            ├── pseudobulk_methylation/             160 resources
            │   ├── Human/                           40 resources
            │   │   ├── Astro/
            │   │   │   ├── CGN
            │   │   │   └── CHN
            │   │   ├── CLA/
            │   │   │   ├── CGN
            │   │   │   └── CHN
            │   │   ├── ...
            │   │   └── Vsc/
            │   │       ├── CGN
            │   │       └── CHN
            │   ├── Macaque/                         40 resources
            │   ├── Marmoset/                        40 resources
            │   └── Mouse/                           40 resources
            ├── pseudobulk_hic/                      80 resources
            │   ├── Human/                           20 resources
            │   │   ├── Astro
            │   │   ├── CLA
            │   │   ├── ...
            │   │   └── Vsc
            │   ├── Macaque/                         20 resources
            │   ├── Marmoset/                        20 resources
            │   └── Mouse/                           20 resources
            └── supplementary_table/                 47 resources
The data are organized into eight resource groups. **atac_fragments** currently contains 22 sample-level resources with chromatin-accessibility fragment data generated by 10x Multiome. Each fragment record gives the genomic location of an ATAC fragment and the nucleus it came from. **rna\_expression\_atac\_matrix** contains 23 sample-level resources corresponding to the 23 10x Multiome sample/library preparations. Each resource contains a joint RNA-expression and ATAC-peak matrix for individual nuclei. **rna\_expression\_matrix** contains four species-level RNA expression matrices corresponding to human, macaque, marmoset, and mouse. Each matrix combines nuclei from multiple samples of the same species and includes cell-level annotations such as sample identity and cell subclass. **pseudobulk\_atac** and **pseudobulk\_rna** each contain 80 cell-type-specific bigWig resources derived from the 10x Multiome data. For each modality, 20 cell types are represented in each of the four species, giving 20 × 4 = 80 resources. The ATAC tracks represent chromatin-accessibility signal aggregated across nuclei of the same cell type, while the RNA tracks represent aggregated RNA-sequencing coverage for the corresponding cell populations. **pseudobulk\_methylation** contains 160 resources derived from the snm3C-seq data. For each of the four species, 20 cell types are represented, with separate CGN and CHN methylation tracks for each cell type, giving 20 × 2 × 4 = 160 resources. **pseudobulk_hic** contains 80 Hi-C resources derived from the snm3C-seq data, with 20 cell types represented in each of the four species. These resources contain 3D chromatin-contact data aggregated by cell type. Note that the cell-type labels used for the methylation and Hi-C resources are different from those used for the pseudobulk RNA and ATAC resources. The **supplementary\_table** collection contains 47 resources corresponding to the supplementary tables and their subdivisions provided with the study. The table below shows the correspondence between the ATAC-fragment resources and the sample-level RNA expression/ATAC matrix resources for the 23 10x Multiome preparations. | Species | ATAC fragment resource | RNA expression/ATAC matrix resource | |---|---|---| | Human | M1\_donor1\_deep2 | M1\_donor1 | | Human | M1\_donor1\_neun\_deep | M1\_donor1\_neun | | Human | M1\_donor2\_deep2 | M1\_donor2 | | Human | M1\_donor2\_neun\_deep | M1\_donor2\_neun | | Human | M1\_donor3\_deep | M1\_donor3 | | Human | M1\_donor3\_neun\_deep | M1\_donor3\_neun | | Human | — | M1\_donor3\_rep2 | | Macaque | M1\_Dheni\_deep2 | M1\_Dheni | | Macaque | M1\_Dheni\_neun\_deep | M1\_Dheni\_neun | | Macaque | M1\_mac3\_deep | M1\_mac3 | | Macaque | M1\_R2\_deep2 | M1\_R2 | | Marmoset | M1\_meadow\_deep | M1\_Meadow | | Marmoset | M1\_peregrine\_A\_deep2 | M1\_Peregrine\_rep1 | | Marmoset | M1\_peregrine\_B\_deep2 | M1\_Peregrine\_rep2 | | Marmoset | M1\_webster\_deep | M1\_Webster | | Mouse | 2C\_rep1\_deep | Mop\_2C\_rep1 | | Mouse | 2C\_rep2\_deep | Mop\_2C\_rep2 | | Mouse | 3C\_rep1\_deep | Mop\_3C\_rep1 | | Mouse | 3C\_rep2\_deep | Mop\_3C\_rep2 | | Mouse | 4B\_rep1\_deep | Mop\_4B\_rep1 | | Mouse | 4B\_rep2\_deep | Mop\_4B\_rep2 | | Mouse | 5D\_rep1\_deep | Mop\_5D\_rep1 | | Mouse | 5D\_rep2\_deep | Mop\_5D\_rep2 | Note: The ATAC-fragment resource corresponding to M1\_donor3\_rep2 is currently missing.