# CHANGE OF GRANTEE INSTITUTION -  Deconstructing The Hematopoietic Stem Cell Niche

> **NIH NIH K01** · BOSTON MEDICAL CENTER · 2021 · $148,889

## Abstract

Project Summary/Abstract
The hematopoietic stem cell (HSC) niche is a specialized microenvironment that supports the life-long self-
renewal of HSCs and their ability to produce all blood cell lineages. A number of different cell types and
molecular factors have been associated with HSC niches in the mammalian bone marrow. To date, however,
the challenges of directly visualizing the bone marrow have precluded a rigorous, systematic investigation of
the cell-cell interactions that promote the niche engraftment of HSCs. Zebrafish offer an unparalleled setting in
which the dynamic interactions between HSCs and their supporting niche cells can be experimentally
manipulated and directly visualized at a resolution and throughput not possible in any other organism. The
overarching goal of this proposal is to use live cell imaging in the zebrafish embryo, in combination with new
technologies in gene expression analysis and tissue-specific gene disruption, to elucidate novel cellular and
molecular mechanisms that are required for the engraftment of HSCs within their niche. The goal of the first
aim is to integrate multiple spatial and tissue-specific gene expression datasets to generate a comprehensive
map of gene expression within the zebrafish caudal hematopoietic tissue (CHT), a transient HSC niche akin to
the mammalian fetal liver. The resulting map of cell-specific gene expression will be used to guide functional
investigations of the cell-cell interactions that are required for HSC engraftment within the CHT. This gene
expression data will be used to generate a reporter transgene that specifically labels stromal cells in the CHT.
In addition, this gene expression data will be used, in combination with a tissue-specific CRISPR system, to
identify the cellular adhesion molecules that mediate macrophage-HSC interactions and are required for HSC
engraftment in the CHT. The second aim will investigate the effects of oxidative stress on the HSC niche within
the CHT. This will be done by treating embryos with compounds that induce oxidative stress in combination
with a live cell dye that permits visualization of reactive oxygen species (ROS). Additionally, the function of two
genes (sepp1a and nrros), with known roles in maintaining low ROS levels, will be investigated using loss-of-
function and overexpression experiments. These studies could identify novel therapeutic targets to enhance
the engraftment and maintenance of HSCs during transplantation-based treatment of blood disorders.
 As a postdoctoral fellow, Dr. Hagedorn will conduct his research in the laboratory of Dr. Leonard Zon, a
renowned hematologist and stem cell biologist. Building on a strong background in genetic and live cell
imaging, Dr. Hagedorn will expand his expertise to include new technologies in spatial gene expression and
tissue-specific gene disruption. Under the guidance of Dr. Zon and an exceptional mentoring committee, Dr.
Hagedorn has constructed a rigorous research and traini...

## Key facts

- **NIH application ID:** 10242046
- **Project number:** 5K01DK111790-06
- **Recipient organization:** BOSTON MEDICAL CENTER
- **Principal Investigator:** Elliott Jennings Hagedorn
- **Activity code:** K01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $148,889
- **Award type:** 5
- **Project period:** 2017-09-01 → 2024-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10242046

## Citation

> US National Institutes of Health, RePORTER application 10242046, CHANGE OF GRANTEE INSTITUTION -  Deconstructing The Hematopoietic Stem Cell Niche (5K01DK111790-06). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10242046. Licensed CC0.

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