# Effects of Erythropoietin on Bone Marrow Stroma

> **NIH NIH F31** · UNIVERSITY OF CINCINNATI · 2022 · $28,972

## Abstract

ABSTRACT
Millions of individuals worldwide are affected by hypoproliferative anemias, such as anemia of inflammation or
myeloodysplastic syndrome (MDS). Erythropoietin (Epo) is a central regulator of erythropoiesis and is known to
act directly on erythroid progenitors and precursors. Non-erythroid cells have been shown to be responsive to
Epo via expression of the erythropoietin receptor (EpoR), which may be important in the context of erythroid
progenitor and precursor niches. Hematopoietic progenitors are known to reside in the vascular endothelial
niche. We have recently found that endothelial cells of EpoR-Cre tdTomato mice show robust tdTomato signal,
indicating that Epo signaling may play a role in this niche. Conflicting reports exist about the presence of EpoR
within the erythroblastic island (EBI) macrophage (Mφ), which is the erythroid precursor niche. We have
recently published that EBI Mφs show a heterogeneous phenotype, indicating that more investigation is
needed to determine the expression pattern of EpoR in this niche. Knowing that non-erythroid cells have the
capacity to respond to Epo, it will be essential to understand how specifically the erythroid niches respond to
Epo treatment. The long-term goal of this project is to provide insight to the structure and function of erythroid
progenitor and precursor niches to improve the outcome for patients with hypoproliferative anemia, such as
anemia of inflammation or myelodysplastic syndrome, where erythroid-extrinsic factors compromise
erythropoiesis. The objectives of this proposal are to determine how EpoR expression in the vascular
endothelial cells impacts the erythroid progenitor production and determine the expression pattern of EpoR in
the EBI Mφ population and its functional consequence to the erythroid precursors in the EBIs. To meet these
objectives, the progenitor and precursor niches will be evaluated in each aim. We will validate the active
presence of EpoR, by quantifying downstream signaling readouts and we will evaluate the significance of
EpoR signaling in the bone marrow stroma utilizing mouse models of tissue specific deletion of EpoR, breeding
the EpoRflox/flox mouse with Tie2Cre mice and Csf1RCre mice to delete EpoR in endothelial cells and Mφs
respectively. To evaluate the effect of EpoR in the progenitor niche, erythroid progenitors will be quantified in
Tie2Cre;EpoR∆/∆ mice by colony assays and flow cytometry. Downstream readouts of EpoR signaling will also
be evaluated to determine the presence of EpoR in EBI Mφs. Tissue-specific (Csf1R-Cre driven) deletion in
Mφs will determine the functional significance of EpoR signaling within EBI Mφs in terms of erythroid precursor
population. Because EBI Mφs are heterogeneous, it will be necessary to characterize transcriptomic and
proteomic changes in the presence and absence of Epo with single cell resolution. Our studies will evaluate
the BM stromal cells serving as niches for erythroid precursors and progenitors and...

## Key facts

- **NIH application ID:** 10388031
- **Project number:** 1F31HL158185-01A1
- **Recipient organization:** UNIVERSITY OF CINCINNATI
- **Principal Investigator:** Laurel Romano
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $28,972
- **Award type:** 1
- **Project period:** 2022-04-01 → 2022-11-25

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10388031

## Citation

> US National Institutes of Health, RePORTER application 10388031, Effects of Erythropoietin on Bone Marrow Stroma (1F31HL158185-01A1). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10388031. Licensed CC0.

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