Center for Multiomic Human Brain Cell Atlas

Grant at a glance

Short name

BICAN_Mul_PN_Human

Grant number

UM1MH130994

Funding agency

NIMH

Program

bican

Description

Understanding cell identities and their spatial distributions throughout different regions of the human brain is a fundamental step when trying to integrate physiological, behavioral, neurochemical and molecular data. At present, although major categories of the cell-types present in the human brain have been defined molecularly, the different subtypes within these categories along with their locations are far from understood. Gene expression drives cell programs and states that underlie distinct brain functions. Open chromatin and modified histones mark gene-regulatory elements that control cell type-specific gene expression patterns. Cytosine DNA methylation (mC) is a stable epigenomic signature that persists in post-mitotic cells throughout their lifetime, defining their cellular identity. Single-cell gene expression, open chromatin profiles and DNA methylation assays have been successfully used to identify distinct cell types in an unbiased fashion in heterogeneous tissues including the human brain. This UM1 proposal builds on our earlier successes in mouse brain mapping to produce detailed single-cell multimomic and spatial cell maps at the single-cell level across 100 anatomically defined regions in the human brain. Profiling human brain samples will permit the discovery of unique gene expression patterns for each molecularly-defined cell type, identify their spatial organization, and their specific non-coding DNA regulatory regions. Multi-modal integration between epigenomic and transcriptomic signatures will allow the identification of new cell types and unique cell-type markers that will rapidly be made available to the entire community. This UM1 project will also provide new tools for genetic access of previously inaccessible brain regions as well as facilitate the functional analysis of genetic variants associated with neuropsychiatric and neurological disorders.

Collections from this grant

Associated labs

• ucsd_ren
• salk_ecker

Methods supported

Modalities

epigenome multimodal genome transcriptome

Techniques

m3c-seq droplet paired-tag; RNA multiplex droplet paired-tag; RNA droplet paired-tag; DNA multiplex droplet paired-tag; DNA whole genome sequencing Stereo-seq 10x chromium 3' v3.1 sequencing 10X genomics multiome;atac-seq 10X genomics multiome;rnaseq 10xV3.1_HT_CellPlex;Barcode 10xV3.1_HT 10xV3.1_HT_CellPlex;GEX 10x Chromium 3' v4 sequencing 10xV3.1_CellPlex;Barcode 10xV3.1_CellPlex;GEX snmCT-seq 10x chromium 3' v3 sequencing smart-seq v4 10x chromium 5' v3 sequencing 10x chromium 5' v5.2 sequencing SMARTSeqSC 10x Chromium 3' v4-OCM sequencing 10xV3.1_LT

Assays

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

Taxa