# Spatial registration of gene expression in the human brain

> **NIH NIH U01** · LIEBER INSTITUTE, INC. · 2020 · $904,464

## Abstract

Project Summary/Abstract
Extensive effort has been committed to more fully characterize the human brain transcriptome within and
across cell types to better understand changes in RNA expression associated with brain development and
aging, developmental or psychiatric brain disorders, and local genetic variation. Large consortia, including
psychENCODE, have primarily focused on the molecular profiling of RNA extracted from homogenate/bulk
tissue from different brain regions across hundreds of individuals, though single nuclei expression approaches
are increasingly being utilized in the second phase of projects. While these differences in signatures across
brain regions relate to the unique cell types underlying each region, the specific cell types and their
corresponding spatial landscapes are largely unknown.
Neurons in different cortical and hippocampal layers show distinct expression patterns, morphology, physiology
and patterns of connectivity. Converging evidence suggests that impairments in the formation or maintenance
of synapses may be involved in schizophrenia, and studies in the postmortem brains of subjects have pointed
to specific cell types and revealed differences in neuronal and synaptic structure that are localized to specific
layers, suggesting that genetic risk for schizophrenia may manifest with laminar specificity. In this application,
we propose to generate detailed spatial transcriptomics maps of the human DLPFC and hippocampus. These
spatial expression maps will be combined with complementary single nuclei sequencing data from the same
tissue blocks to develop spatial "registration" approaches that can add spatial information to existing single
nuclei datasets in the psychENCODE project. We will combine these spatial and cell type-specific maps to
implicate layer- and cell-specific populations in schizophrenia genetic risk and illness state that will be validated
using complementary in situ hybridization techniques.
These rich spatial transcriptome maps will add another dimension to existing and forthcoming single nuclei
RNA-seq datasets in the frontal cortex and hippocampus to further refine the cell types in the human brain and
their subsequent dysregulation in debilitating brain disorders.

## Key facts

- **NIH application ID:** 9961969
- **Project number:** 1U01MH122849-01
- **Recipient organization:** LIEBER INSTITUTE, INC.
- **Principal Investigator:** Keri Martinowich
- **Activity code:** U01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $904,464
- **Award type:** 1
- **Project period:** 2020-05-01 → 2022-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9961969

## Citation

> US National Institutes of Health, RePORTER application 9961969, Spatial registration of gene expression in the human brain (1U01MH122849-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9961969. Licensed CC0.

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