# Intravital analysis of hematopoietic stem cells in their bone marrow niche - Resubmission - 1

> **NIH NIH R01** · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · 2022 · $650,581

## Abstract

ABSTRACT
Hematopoietic stem cells (HSC) in the adult mammalian bone marrow (BM) are rare multipotent cells that
can regenerate and sustain multilineage hematopoiesis upon transplantation. Given the rarity and limited
availability of HSC in the BM, strategies to "mobilize" HSC from the BM to the peripheral blood show great
promise to enhance the efficiency of hematopoietic reconstitution. On the other hand, the reconstitution
capacity of HSC can be impaired in old age or following inflammatory insults. HSC are localized in a unique
functional BM compartment called the niche. Its key component is a network of perivascular stromal cells
expressing the HSC growth factor stem cell factor (SCF or Kit ligand) and chemokine CXCL12, whose
receptor CXCR4 helps retain HSC in the BM. However, the morphology and dynamics of endogenous live
HSC and their interactions with the BM niche components have not been well characterized. We have
developed a system for specific fluorescent labeling of adult murine HSC, and adapted it for intravital
imaging of HSC within the BM. Preliminary studies revealed an unexpectedly dynamic morphology and
complex motility of HSC in the steady state. Furthermore, we were able to visualize interactions between
live HSC and the stromal cells. We will apply this system to systematically study the behavior of live HSC
and their interaction with the niche in live animals. The project involves a collaboration between labs with
the expertise in genetic manipulation and analysis of HSC (Reizis), intravital microscopy of the BM
(Fooksman) and computational analysis and modeling of cell behavior (Krichevsky). In Aim 1, we will
visualize the behavior of live HSC in the BM in the steady state and during inflammation. In Aim 2, we will
characterize the interaction of HSC with their BM environment, both in normal conditions and after
mobilization from the BM. In Aim 3, we will analyze the molecular basis of HSC dynamics and correlate it
with HSC function in supporting hematopoiesis. The proposed studies would address major gaps in our
knowledge of basic HSC biology, and provide novel insights into the clinically relevant process of HSC
mobilization.

## Key facts

- **NIH application ID:** 10491048
- **Project number:** 5R01HL152637-02
- **Recipient organization:** NEW YORK UNIVERSITY SCHOOL OF MEDICINE
- **Principal Investigator:** David R Fooksman
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $650,581
- **Award type:** 5
- **Project period:** 2021-09-20 → 2025-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10491048

## Citation

> US National Institutes of Health, RePORTER application 10491048, Intravital analysis of hematopoietic stem cells in their bone marrow niche - Resubmission - 1 (5R01HL152637-02). Retrieved via AI Analytics 2026-06-11 from https://api.ai-analytics.org/grant/nih/10491048. Licensed CC0.

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