# Spatiotemporal epigenomic and chromosomal architectural cell atlas of developing human brains

> **NIH NIH U01** · UNIVERSITY OF CALIFORNIA LOS ANGELES · 2022 · $1,063,112

## Abstract

PROJECT SUMMARY
The adult human brain is comprised of numerous cell types exhibiting specific transcriptomic and epigenomic
signatures associated with their spatial location, connectivity, and function. Although systematic efforts are
underway to characterize cell types in the adult human brain, the transitional cell types and cell states in
developing human brains are not fully defined. Our project will use epigenomic and three-dimensional (3D)
chromosomal architectural information to classify developmental cell types and identify key regulatory dynamics
that may underlie cellular lineage commitment and maturation. Single-cell DNA methylation and chromatin
accessibility profiles have been successfully used to de novo identify distinct cell types in developing and adult
brains. The single-nucleus joint profiling of DNA methylation and chromatin conformation by sn-m3C-seq
provides unique information to identify enhancer-gene looping and provides a resource to link genetic variants
associated with neuropsychiatric disorders to genes. Cell types identified with epigenomic information will be
integrated with spatial transcriptomic signatures using our innovative single-cell joint profiling method of
transcriptome and DNA methylation snmCT-seq. We will determine the spatial and temporal dynamics of
developing brain cell types using multiplexed RNA in situ and Digital Spatial Profiling (DSP) assays. We will
apply state-of-the-art approaches to integrate multiple data modalities to identify progenitor and transitional cell
types, lineage-specific regulatory elements, and enhancer-gene 3D interactions. We will construct cell-type-
specific predictive models of cellular trajectory and gene regulation during brain development by integrating
transcription factor-gene interaction information with time- and pseudotime-series genomics data. The cell type
and regulatory elements catalog of human brain development generated by our project will aid the identification
of developing brain cell types involved in neuropsychiatric disorders and regulatory regions susceptible to
perturbation by disease-associated variants.

## Key facts

- **NIH application ID:** 10523974
- **Project number:** 1U01MH130995-01
- **Recipient organization:** UNIVERSITY OF CALIFORNIA LOS ANGELES
- **Principal Investigator:** Chongyuan Luo
- **Activity code:** U01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $1,063,112
- **Award type:** 1
- **Project period:** 2022-09-01 → 2027-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10523974

## Citation

> US National Institutes of Health, RePORTER application 10523974, Spatiotemporal epigenomic and chromosomal architectural cell atlas of developing human brains (1U01MH130995-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10523974. Licensed CC0.

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