# Highly scalable and sensitive spatial transcriptomic and epigenomic sequencing of brain tissues from human and non-human primate

> **NIH NIH RF1** · YALE UNIVERSITY · 2021 · $2,896,455

## Abstract

SUMMARY
The human nervous system is possibly the most complex biological tissue, organized into multiple functionally
distinct regions and comprised of over 200 billion neural and non-neural cells, requiring novel scalable tools to
profile cell types and relationships in the tissue context with high spatial resolution. Recently, we developed
DBiT-seq (high-spatial-resolution multi-omics sequencing via deterministic barcoding in tissue), which has
demonstrated (i) high sensitivity (~5,000 UMIs per 10µm pixel), (ii) versatility as it does not require
micropatterned DNA barcode arrays but only a set of reagents, and (iii) adoptability by potential users with no
experience in advanced single molecule imaging or microfluidics. This BICCN project is capitalized on this
novel technology developed by PI Rong Fan (Biomedical Engineer) and the long-standing experience of MPI
Nenad Sestan (Neuroscience) in genomic analysis of human and non-human primate brain tissues, to further
develop DBiT-seq into a highly scalable tool for BICCN to perform high-throughput, high-sensitivity, high-
spatial-resolution, genome-wide mapping of brain tissues. Uniquely, we propose to develop a groundbreaking
first-of-its-kind spatial epigenome sequencing technology based on deterministic barcoding in tissue, which
may open up a new direction in the field of spatial omics research. We will apply spatial transcriptomics and
spatial epigenomics to the mapping of 6 brain regions in human and non-human primate. Spatial omics data
will be integrated with single-nucleus RNA-seq and ATAC-seq to generate spatially-resolved transcriptomic
and epigenomic cell census at an unprecedented level. The contributions of this project to the BICCN
consortium include: (1) fundamental knowledge on diverse cell types and their transcriptional and epigenomic
characteristics in the context of 3D tissue organization in the brain and (2) validated high throughput and
scalable approaches to characterizing cell diversity in human and/or non-human primate brain tissues. The
resulting data will lead to a better understanding of the relationship between brain tissue organization, function,
and epigenetic underpinnings. The technologies can be readily adopted by a BRAIN Initiative community and
the data can be compared or integrated with datasets generated by other BICCN investigators

## Key facts

- **NIH application ID:** 10370074
- **Project number:** 1RF1MH128876-01
- **Recipient organization:** YALE UNIVERSITY
- **Principal Investigator:** Rong Fan
- **Activity code:** RF1 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $2,896,455
- **Award type:** 1
- **Project period:** 2021-09-15 → 2025-09-14

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10370074

## Citation

> US National Institutes of Health, RePORTER application 10370074, Highly scalable and sensitive spatial transcriptomic and epigenomic sequencing of brain tissues from human and non-human primate (1RF1MH128876-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10370074. Licensed CC0.

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