# Skeletal heterogeneity of bone marrow stress responses.

> **NIH NIH R01** · CINCINNATI CHILDRENS HOSP MED CTR · 2024 · $518,603

## Abstract

Abstract:
Defining how the bone marrow functions under stress is indispensable to understand
hematopoiesis during disease. A major limitation in the field is that most studies (including those
from our group) have ignored the fact that hematopoiesis takes place in multiple bones. Instead,
the field has largely focused on investigating hematopoiesis in long bones – as these are readily
accessible and yield large amounts of hematopoietic cells for analyses- and assumed that the
rest of the skeleton behaved in a similar manner. We have demonstrated that the bone marrow
response to a hematopoietic insult is dramatically different depending on the bone examined. In
this proposal we want to understand the cellular mechanisms driving these heterogeneous
responses.
We have found that -after treatment with G-CSF- the sternum shows reduced numbers of
neutrophils and neutrophil progenitors while long bones show expansions in these populations.
In response to hemorrhage both the sternum and the tibia increase erythrocyte production,
however, the skull fails to increase erythropoiesis. Based on this we hypothesize: a) the bone
marrow response to stress is variable across the skeleton; b) some bones have specialized to
preferentially respond to specific insults; c) this is non-autonomously regulated by the unique
composition -and anatomy- of the microenvironment in each bone.
We will test this hypothesis in two aims. In Aim 1 we will determine how bone marrow
macrophages control the differential response to G-CSF in sternum vs long-bones. In Aim 2 we
will whether competition between erythroid progenitors and trabecular bone controls stress
erythropoiesis.

## Key facts

- **NIH application ID:** 11018912
- **Project number:** 1R01DK141465-01
- **Recipient organization:** CINCINNATI CHILDRENS HOSP MED CTR
- **Principal Investigator:** Daniel Lucas
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $518,603
- **Award type:** 1
- **Project period:** 2024-09-20 → 2029-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11018912

## Citation

> US National Institutes of Health, RePORTER application 11018912, Skeletal heterogeneity of bone marrow stress responses. (1R01DK141465-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/11018912. Licensed CC0.

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