# Biochemistry of Leukemia Virus Core-Binding Factor

> **NIH NIH R01** · UNIVERSITY OF PENNSYLVANIA · 2021 · $625,577

## Abstract

Summary
The goal of this proposal is to understand how hematopoietic stem cells (HSCs) form in the
embryo. All HSCs in the adult bone marrow are descendants of pre-hematopoietic stem cells (pre-
HSCs) that differentiate from hemogenic endothelial (HE) cells in the major caudal arteries of the
embryo. However, only a subset of hematopoietic cells that differentiate from HE cells in the
arteries are pre-HSCs, while many are committed lympho-myeloid biased progenitors. We
generated a comprehensive single cell dataset that captures the entire developmental trajectory
from arterial endothelial cells to lympho-myeloid biased progenitors and pre-HSCs. This dataset
is a powerful tool for generating and testing novel concepts in HSC ontogeny. One discovery from
this analysis is an endothelial cell precursor of HE cells that we named pre-HE. Pre-HE cells are
a transitional population from which a limited number of cells will be specified as HE. We
discovered that the efficiency at which pre-HE cells differentiate into HE cells is determined by
the levels of RUNX1, a transcription factor that is expressed in HE cells and is essential for HE
cell specification. We also identified a candidate enhancer in the Runx1 gene that first becomes
accessible in pre-HE cells. One goal of this proposal is to determine if the Runx1 pre-HE enhancer
is required for the differentiation of pre-HE cells into HE cells, and which transcription factors and
upstream signaling pathways regulate the activity of this enhancer. A second important finding is
that we defined the molecular differences between lympho-myeloid biased progenitors and pre-
HSCs, and identified genes specifically expressed in each of these populations. One of these
genes, Mecom, which is known to regulate adult HSC proliferation and function, is more highly
expressed in pre-HSCs than in lympho-myeloid biased progenitors. We will determine if the
expression of Mecom in endothelial cells regulates the number of pre-HSCs that are generated
during hematopoietic ontogeny. Understanding how arterial HE cells are specified and specialized
will help guide ongoing efforts to generate HSCs from other cell sources.

## Key facts

- **NIH application ID:** 10209705
- **Project number:** 2R01HL091724-28
- **Recipient organization:** UNIVERSITY OF PENNSYLVANIA
- **Principal Investigator:** NANCY SPECK
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $625,577
- **Award type:** 2
- **Project period:** 1993-08-10 → 2025-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10209705

## Citation

> US National Institutes of Health, RePORTER application 10209705, Biochemistry of Leukemia Virus Core-Binding Factor (2R01HL091724-28). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10209705. Licensed CC0.

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