# Deciphering the regulatory code that specifies different cell fates in development using single cell genomics

> **NIH NIH R01** · YALE UNIVERSITY · 2020 · $571,816

## Abstract

Summary
The vertebrate embryo contains hundreds of functionally diverse cell types, however we lack a complete
understanding of the regulatory code that specifies each cell type and how disruptions in this code affect
relationships between lineages. Here, we propose two aims to dissect the accessible regions of the chromatin,
the regulatory motifs and the putative transcription factors that mediate the specification of multiple cell types
during embryogenesis. First, (Aim 1), we will utilize single cell ATAC-seq and scRNA-seq to uncover the
dynamics of chromatin accessibility and the transcriptional profiles that define discrete cell types during early
development. We will define the regulatory motifs in accessible regions of the chromatin that are preferentially
engaged in different cell types. Second (Aim 2), we will use manifold learning approaches to define co-
regulated gene modules and apply a regulatory network inference framework for scRNA-seq and scATAC-seq
data, and test the regulatory interactions by mutating key pioneer factors and investigate how they cooperate
with other TFs to regulate chromatin accessibility and cell differentiation during development. This project will
generate extensive, high-quality datasets as well as novel computational methods to enable quantitative and
predictive models of embryonic development with the goal to decipher the gene regulatory network specifying
cellular identity during development. Given that early development is conserved across vertebrate species, our
findings have the potential to inform human development, and lay the foundation to investigate the etiologies of
human developmental disorders and to engineer novel cell types and lineages in vitro for regenerative
medicine.

## Key facts

- **NIH application ID:** 9974094
- **Project number:** 1R01HD100035-01A1
- **Recipient organization:** YALE UNIVERSITY
- **Principal Investigator:** Antonio J Giraldez
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $571,816
- **Award type:** 1
- **Project period:** 2020-05-07 → 2025-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9974094

## Citation

> US National Institutes of Health, RePORTER application 9974094, Deciphering the regulatory code that specifies different cell fates in development using single cell genomics (1R01HD100035-01A1). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9974094. Licensed CC0.

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