# Molecular and functional dissection of the zebrafish hematopoietic stem cell niche

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA, SAN DIEGO · 2024 · $406,941

## Abstract

Project Summary/Abstract:
Hematopoietic stem cells (HSCs) give rise to all terminally differentiated cells in the blood. The ability of HSCs
to reconstitute these blood cell lineages for life underlies the efficacy of bone marrow transplantation therapy
for treatment of various blood disorders, including leukemias, anemia, and autoimmunity. Although this is an
established and effective treatment, two-thirds of patients in need of a transplant lack a matched donor.
Therefore, alternative sources of therapeutic HSCs would be a boon to the field. Human pluripotent stem cells
(hPSCs) represent a potential source for cell-based therapies, including the derivation of patient-specific
transplantable HSCs, which would additionally circumvent immune rejection and alloreactivity, both major
issues in the clinic.
The goal of the proposed research is to extend our preliminary observations on a novel population of somite-
derived endothelial cells (SDECs). Of note, these cells migrate exclusively to the nascent dorsal aorta and act
as a developmental niche for the subsequent emergence of HSCs. Characterization of SDECs will provide a
deeper understanding of the cues that govern HSC development in vivo. The fundamental discoveries made
in the course of these studies will ultimately inform derivation strategies of HSCs from hPSCs. This proposal
will leverage lineage tracing methods in zebrafish and in vitro differentiation protocols of hPSCs combined with
single-cell sequencing approaches to determine the molecular mechanisms of this requirement, and to provide
a new level of understanding of how posterior lateral mesoderm is instructed to generate HSCs.
The long-term goal of these studies is to gain a better understanding of how HSCs develop in the embryo in
order to translate this information to hPSCs. Successful completion of this research will have a profound
impact on HSC derivation and expansion, and thereby will be instrumental in overcoming current obstacles to
the effective treatment of diseases requiring bone marrow transplant therapy.

## Key facts

- **NIH application ID:** 10775723
- **Project number:** 5R01DK074482-18
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN DIEGO
- **Principal Investigator:** David Traver
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $406,941
- **Award type:** 5
- **Project period:** 2006-05-08 → 2024-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10775723

## Citation

> US National Institutes of Health, RePORTER application 10775723, Molecular and functional dissection of the zebrafish hematopoietic stem cell niche (5R01DK074482-18). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10775723. Licensed CC0.

---

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