An Atlas of Human Brain Cell Variation

Grant at a glance

Short name

BICAN_PN_Human_Var

Grant number

UM1MH130966

Funding agency

NIMH

Program

bican

Description

The human brain exhibits profound diversity in biological function and vulnerability to disease. Despite the biomedical and cultural importance of inter-individual variation, we know relatively little about its underlying cellular and molecular substrates. In this work we will leverage new technologies in single-cell and spatial genomics to construct an Atlas of Human Brain Cell Variation. We will analyze tens of millions of cells from more than 200 people by single-nucleus RNA-seq and single-nucleus ATAC-seq, and a subset of these by spatial transcriptomics. Analysis of these data will seek to understand: the static versus dynamic molecular and spatial features of each cell type; the ways in which human genetic variation shapes the molecular repertoire of each cell type; and the constellations of cellular and molecular features that co-vary, appearing together in the same brains. We seek especially with this work to understand the functional connections between these phenotypes and: (i) the gene regulatory processes that drive and shape it; (ii) genetic variation associated with brain diseases; and (iii) structural brain variation measured in hundreds of neuroimaging studies. The project will deliver an essential data resource for cellular, molecular, genetic and translational neuroscience – while expanding our understanding of the ways the human brain varies across different people.

Collections from this grant

Associated labs

• broad_mccarroll

Methods supported

Modalities

transcriptome multimodal epigenome

Techniques

10x chromium 3' v3.1 sequencing 10x Chromium 3' v4 sequencing Slide-tag_10x5Pv2;Spatial Slide-tag_10x5Pv2;GEX 10X genomics multiome;rnaseq 10X genomics multiome;atac-seq 10x chromium 5' v3 sequencing Slide-tag std 10x 5' v2 sequencing PIPSeq T20 3' v4+ PIPSeq T2 3' v4+ 10x chromium 5' v5.2 sequencing m3c-seq 10xV3.1_HT_CellPlex;Barcode 10xV3.1_HT 10xV3.1_HT_CellPlex;GEX 10xV3.1_CellPlex;Barcode 10xV3.1_CellPlex;GEX snmCT-seq 10x Chromium 3' v4-OCM sequencing 10x chromium 3' v3 sequencing smart-seq v4 droplet paired-tag; DNA droplet paired-tag; RNA multiplex droplet paired-tag; RNA SMARTSeqSC 10xV3.1_LT

Assays

transcriptome spatial transcriptome multiome; transcriptome multiome; chromatin methylation HT; transcriptome transciptome; cellplex_barcode transciptome; cellplex_RNAseq HT; cellplex_barcode HT; cellplex_RNAseq multimodal LT; transcriptome

Taxa