# HEMANGIOBLAST DEVELOPMENT AND REGULATION

> **NIH NIH R01** · WASHINGTON UNIVERSITY · 2020 · $456,657

## Abstract

Formation of functional blood and its conduit vascular system is requisite for successful embryogenesis.
The ETS transcription factor ETV2 has emerged as a critical regulator of hematopoietic and vascular
development. In particular, ETV2 is required at the earliest stage in the formation of hematopoietic and
endothelial cell lineages with its deficiency leading to a complete block in blood and vessel formation. At the
molecular level, ETV2 positively activates genes essential for hematopoietic and endothelial cell lineage
specification. At the cellular level, ETV2 is crucial for restricting FLK1+ mesoderm to the FLK1+
hemangiogenic mesoderm, which generates hematopoietic and endothelial cell lineages. Importantly, ETV2
function is evolutionary conserved, as mouse or human ETV2 can induce hematopoietic and vascular
program in zebrafish. Moreover, hematopoietic and endothelial cells can be more efficiently generated from
mouse and human pluripotent stem cells by enforced Etv2 expression. Human somatic cells can also be
reprogrammed to endothelial cells by the inclusion of Etv2. These findings suggest a unique and essential
function played by this factor in vertebrates and relevance in humans with the strong potential for
translational applications. However, we currently have very limited knowledge on the upstream regulators of
Etv2 expression. Whether ETV2 requires cofactor(s) in controlling its target gene expression is also not
known. Our preliminary data suggests that ETV2 specifies hemangiogenic fate in a threshold-dependent
manner and that coordinated function of forkhead transcription factor Foxh1 and Flk1 is required for
achieving Etv2 threshold expression. Our preliminary data also suggests that chromatin remodeling of the
target genes may be required for ETV2 function, as we identified the core regulatory subunit of SWI/SNF
chromatin remodeling complex, BAF155 (aka SRG3 or SMARCC1) to form a complex with ETV2.
Importantly, conditional deletion of Baf155 using Flk1-Cre resulted in embryonic lethality with hematopoietic
defects, further supporting the notion that chromatin remodeling is integral to ETV2 transcriptional function.
From these fundamental findings, we will investigate whether the hemangiogenic fate specification is
achieved through Etv2 threshold expression and the requirements of Foxh1 and Flk1 in achieving the Etv2
threshold expression. We will also investigate whether ETV2 requires SWI/SNF chromatin remodelers in
activating hematopoietic and endothelial cell lineage program. Successful completion of the work will
establish the role for Foxh1, Flk1, Etv2 and the chromatin remodelers in the hemangiogenic fate
specification and will lead to deeper mechanistic understanding of how hematopoietic and vascular
development is regulated. The outcome will also be instrumental for generating hematopoietic and
endothelial cells from pluripotent stem cells or somatic cell reprogramming and function of such cells in a
wide range of applica...

## Key facts

- **NIH application ID:** 9843735
- **Project number:** 5R01HL055337-23
- **Recipient organization:** WASHINGTON UNIVERSITY
- **Principal Investigator:** KYUNGHEE CHOI
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $456,657
- **Award type:** 5
- **Project period:** 1996-08-01 → 2021-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9843735

## Citation

> US National Institutes of Health, RePORTER application 9843735, HEMANGIOBLAST DEVELOPMENT AND REGULATION (5R01HL055337-23). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9843735. Licensed CC0.

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