# Osteomacs and megakaryocytes interact to regulate hematopoietic stem cell function

> **NIH NIH R01** · INDIANA UNIVERSITY INDIANAPOLIS · 2020 · $317,000

## Abstract

The hematopoietic niche is a complex structure of multiple cell types and extra-cellular matrix proteins. In a
well-orchestrated manner, elements of the niche interact together and with hematopoietic stem cells (HSC) to
maintain HSC selfrenewal potential. HSC maintenance within the bone marrow (BM) is associated with the
health of cellular elements of the niche including endothelial cells, osteoblasts, and other hematopoietic cells
such as megakaryocytes. Our published work demonstrates that immature osteoblasts mediate a robust in
vitro hematopoiesis enhancing activity and that megakaryocytes enhance osteoblast proliferation and inhibit
their differentiation. Megakaryocytes have been implicated in both regulating HSC function and maintaining the
competence of the niche after radiation through specialized interactions with osteoblasts that augment their
enhancement of HSC function. Recently, a unique population of CD45+F4/80+ macrophages known as
osteomacs (OM) was recognized in the niche. We detected these cells in neonatal calvarial cell (NCC)
preparations and recently published that OM are critical for the osteoblast-mediated hematopoiesis enhancing
activity. Megakaryocytes stimulate NCC-derived OM as well as OM from adult mice and significantly enhance
their in vitro expansion and function. Interestingly, extensive flow cytometric characterization of OM revealed
that OM are phenotypically distinct from BM-derived macrophages and that the later cannot functionally
substitute for OM to drive the osteoblast-mediated hematopoiesis enhancing activity. Our studies further
suggest that OM are important for the competence of the hematopoietic niche. We hypothesize that
maintenance of HSC function and the competence of the hematopoietic niche are dependent on
cellular interactions and molecular cross talk between osteoblast, OM and megakaryocytes. Our
hypothesis will be examined by investigating the following three aims: 1) Investigate if OM are transplantable
and whether loss of megakaryocytes disrupts the emergence of OM and negatively impacts HSC function and
niche competence. 2) Identify differences between OM and BM-derived macrophages that make OM a unique
niche component and define, at the molecular level, how OM and megakaryocytes promote the maintenance of
HSC function. 3) Define the spatial relationship between HSC, osteoblasts, OM, and megakaryocytes in the
intact niche of young and old mice and in the perturbed microenvironment following marrow conditioning. The
significance of these studies is that they will define and explain how the interplay between four cellular
components of the BM regulate HSC function and the competence of the niche. The novelty derives from the
potential of these studies to establish, for the first time, a unique group of cells, namely OM, as primary targets
of the megakaryocyte-mediated HSC promoting activity in the niche. Our premise that OM are central to HSC
and niche functional properties is both paradigm shi...

## Key facts

- **NIH application ID:** 10017954
- **Project number:** 5R01DK118782-02
- **Recipient organization:** INDIANA UNIVERSITY INDIANAPOLIS
- **Principal Investigator:** Melissa A Kacena
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $317,000
- **Award type:** 5
- **Project period:** 2019-09-15 → 2024-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10017954

## Citation

> US National Institutes of Health, RePORTER application 10017954, Osteomacs and megakaryocytes interact to regulate hematopoietic stem cell function (5R01DK118782-02). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/10017954. Licensed CC0.

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