# Ultra-high Throughout Single Cell Multi-omic Analysis of Histone Modifications and Transcriptome in Mouse and Human Brains

> **NIH NIH RF1** · UNIVERSITY OF CALIFORNIA, SAN DIEGO · 2021 · $3,199,559

## Abstract

Histone modification carries rich epigenetic information that constitutes a mechanism of cellular memory.
Single cell analysis of histone modification in conjunction with transcriptome could help uncover this critical
layer of cellular memory and lead to better definition of cell types and states in the brain. Here, we propose
to develop an ultra-high throughput method, known as Paired-Tag, for joint profiling of histone modifications
and transcriptome in single cells. In preliminary studies, we have demonstrated the feasibility and utility of
this method by applying it to the adult mouse frontal cortex and hippocampus. In the proposed research, we
will further develop and optimize Paired-Tag to enable automation and support large-scale data production
project. Additionally, we will implement a series of quantitative QC metrics to benchmark the performance of
the new Paired-Tag procedure against existing Paired-Tag procedures. We will then use the optimized
experimental procedure to generate adult mouse brain cell atlas of histone modifications and transcriptome
at single cell resolution. We will additionally characterize the dynamic changes in histone modifications and
transcriptome at single cell resolution in the mouse brain across multiple developmental stages. Finally, to
demonstrate proof of principle of Paired-Tag for analysis of human brains, we will use it to assay the prefrontal
cortex (BA46) in adult human brains from 3 males and 3 females.

## Key facts

- **NIH application ID:** 10369242
- **Project number:** 1RF1MH128838-01
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN DIEGO
- **Principal Investigator:** MARIA MARGARITA BEHRENS
- **Activity code:** RF1 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $3,199,559
- **Award type:** 1
- **Project period:** 2021-09-13 → 2024-09-12

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10369242

## Citation

> US National Institutes of Health, RePORTER application 10369242, Ultra-high Throughout Single Cell Multi-omic Analysis of Histone Modifications and Transcriptome in Mouse and Human Brains (1RF1MH128838-01). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/10369242. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*