# Mechanisms of endothelial-to-hemogenic transition mediated by Runx1

> **NIH NIH R01** · CHILDREN'S HOSP OF PHILADELPHIA · 2021 · $373,193

## Abstract

Project Summary
Hematopoietic stem and progenitor cells (HSPCs) differentiate from specialized
endothelial cells in the embryo called hemogenic endothelium (HE). The
transcription factor Runx1 is required for the specification of hemogenic
endothelium and for the endothelial to HSPC transition to occur. However, how
Runx1 does so is poorly understood. Our goal is to apply systems biology
approaches to study the transcriptional regulatory network controlling hemogenic
endothelial specification, including the role of Runx1, additional transcription
factors that cooperate with Runx1, and the order of regulatory events that
promote the process. These studies will not only increase our understanding of
the normal developmental process of HSPC formation, but will help guide
attempts to generate hematopoietic stem cells (HSCs) from endothelial cells, ES,
or iPS cells for the treatment of disease. In Aim 1, we will identify Runx1 target
genes in embryonic endothelial cells that are competent to respond to Runx1, and
examine the genome-wide chromatin modifications and gene expression changes that
take place when Runx1 binds its target genes. In Aim 2, we will develop an advanced
graph-theoretic method to identify key TFs that cooperate with Runx1 in embryonic
endothelial cells to induce HE and form blood. We will validate the candidate TFs by
determining their ability to cooperate with Runx1 to induce fetal endothelial cells to
undergo endothelial to HSPC transition and form blood.

## Key facts

- **NIH application ID:** 10183274
- **Project number:** 5R01HD089245-05
- **Recipient organization:** CHILDREN'S HOSP OF PHILADELPHIA
- **Principal Investigator:** NANCY SPECK
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $373,193
- **Award type:** 5
- **Project period:** 2017-08-21 → 2023-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10183274

## Citation

> US National Institutes of Health, RePORTER application 10183274, Mechanisms of endothelial-to-hemogenic transition mediated by Runx1 (5R01HD089245-05). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10183274. Licensed CC0.

---

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