# Erythroblastic island macrophages in normal erythropoiesis and disordered erythropoiesis in polycythemia vera

> **NIH HL R01** · NEW YORK BLOOD CENTER · 2026 · $785,595

## Abstract

ABSTRACT
Erythropoiesis occurs at the erythroblastic island where the central macrophage (EBI M) supports proliferation
and maturation of the surrounding erythroid cells. Alterations in EBI M contribute to the disordered
erythropoiesis in various hematological diseases including polycythemia vera (PV) which is characterized by
erythrocytosis due to V617F mutation in JAK2 (JAK2V/F). In this application, we propose to define the
mechanisms by which EBI M support normal erythropoiesis in Aim 1 and to define the mechanisms by which
JAK2V/F in EBI M contributes to pathogenesis of PV in Aim 2. Our overall hypothesis is that EBI M support
normal erythropoiesis via Epor-Stat5 signaling-mediated production of growth factors Igf1 and Scf as well as iron
carrier transferrin and that JAK2V/F-induced constitutive activation of Epor signaling in the EBI M leads to
upregulation of transferrin receptor CD71 which contributes to the hyperproliferation of EBI M along with
increased production of Igf1 and Scf leading to overproduction of red blood cells that can be alleviated by
interfering with CD71, Igf1-Igf1r axis or/and Scf-cKit axis. Our hypothesis is based on our findings that i) EBI M
expressed EPOR; ii) EPOR+ M expressed Igf1 and Scf as well as iron carrier transferrin (Trf); iii) EPO
stimulation increased the levels of Igf1, Scf and Trf by EBI M; iv) selective deletion of Epor in M led to anemia
along with decreased levels of Igf1, Scf and Trf; v) selective deletion of Igf1 or Trf in M also led to anemia; vi)
although knock-in of Jak2V/F in erythroid cell alone using Gypa-tdTomato-Cre or in M alone using CD169-
tdTomato-Cre led to erythrocytosis in mice, knock-in of Jak2V/F in both erythroid cells and M were required to
fully recapitulate characteristics of human PV; vii) knock-in of Jak2V/F in M led to increased numbers of BM EBI
M and spleen red pulp M along with increased levels of transferrin receptor Trfc (CD71), Igf1 and Scf. In Aim
1, we will generate 

## Key facts

- **NIH application ID:** 11378743
- **Project number:** 5R01HL181370-02
- **Recipient organization:** NEW YORK BLOOD CENTER
- **Principal Investigator:** Xiuli  An
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** HL
- **Fiscal year:** 2026
- **Award amount:** $785,595
- **Award type:** 5
- **Project period:** 2025-08-01T00:00:00 → 2029-04-30T00:00:00

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11378743

## Citation

> US National Institutes of Health, RePORTER application 11378743, Erythroblastic island macrophages in normal erythropoiesis and disordered erythropoiesis in polycythemia vera (5R01HL181370-02). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/11378743. Licensed CC0.

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