# Spatial Control of Myeloid Differentiation

> **NIH NIH R01** · CINCINNATI CHILDRENS HOSP MED CTR · 2021 · $512,253

## Abstract

Abstract:
Mounting evidence indicates that lineage decisions are controlled by local structures that support differentiation
in distinct regions of the bone marrow. Our ability to manipulate hematopoiesis to treat disease has been
hampered by our lack of understanding of these anatomical cues.
We have found that HPC are regionally organized in the BM and that progenitors and immature cells belonging
to the same lineage segregate to different sinusoids. We have also found that there is regional organization to
CSF1 production and that specific BM vessels are critical sources of CSF1 that regulate MDP, monocytes and
dendritic cells but not HSC or macrophages. The central hypothesis is that different subsets of sinusoids
function as assembly lines or hubs that organize and maintain different hematopoietic lineages through the
production of lineage-specific cytokines. We want to understand how these cellular assembly lines function in
the steady-state and after perturbation by acute myeloid leukemia (AML).
We will test this hypothesis in two aims. In Aim 1 we will determine the physiology of these assembly lines
using clonal fate mapping in situ; identifying the components of each assembly line; and conditionally deleting
specific cytokines from key components of each assembly line. In Aim 2 we will investigate how AML inhibits
normal hematopoiesis by perturbing the microenvironment that supports each assembly line.

## Key facts

- **NIH application ID:** 10205426
- **Project number:** 1R01HL153229-01A1
- **Recipient organization:** CINCINNATI CHILDRENS HOSP MED CTR
- **Principal Investigator:** Daniel Lucas
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $512,253
- **Award type:** 1
- **Project period:** 2021-08-15 → 2025-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10205426

## Citation

> US National Institutes of Health, RePORTER application 10205426, Spatial Control of Myeloid Differentiation (1R01HL153229-01A1). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10205426. Licensed CC0.

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