# Coordinate regulation of erythroid and macrophage lineages in development by EKLF/KLF1

> **NIH NIH R01** · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · 2020 · $465,752

## Abstract

SUMMARY
 Erythroid cells mature in vivo in the presence of a supportive macrophage; this cell-cell
compartment is known as the erythroblastic island, an entity first described over 50 years ago. Red cell
interactions with the macrophage are critical for optimal nutrient access, survival, proliferation, and
differentiation of the erythron.
 Our proposed experiments address the exciting idea that Erythroid Krüppel-like Factor (EKLF;
KLF1) not only plays an intrinsic role in establishing the proper gene expression patterns in the red cell
within the erythroblastic island, but that it additionally affects this process by an extrinsic mechanism
based on its surprising expression within the island macrophage and early in development within the
erythro-myeloid progenitor (EMP). Our studies build on observations made in primary or minimally
manipulated cells, aided by in vivo assays and EKLF rescue systems.
 We have found that EKLF is expressed in the EMP in the yolk sac by E8.5. The experiments of
Aim 1 will investigate the role of EKLF in directing the functional potential of these cells at later
stages in the embryo and in the adult.
 We have found that macrophage-restricted ablation of EKLF extrinsically affects the red cell.
The experiments of Aim 2 will examine an iron-related hypothesis for the red cell effect that may
be important for stress recovery.
 We have found that fetal liver island macrophage display a unique gene expression signature
that is extensively regulated by EKLF. The experiments of Aim 3 will assess EKLF's role in island
macrophage identity, studies that will be extended to analysis of human cells.
 Understanding these basic mechanisms will ultimately aid in understanding the problems that
arise in anemias that present with high levels of nucleated red blood cells in circulation, such as
congenital dyserythropoietic anemia (CDA) type IV, and in the design of culture systems that enable
efficient expansion and enucleation of human cell sources for clinical use.

## Key facts

- **NIH application ID:** 9971391
- **Project number:** 1R01DK121671-01A1
- **Recipient organization:** ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
- **Principal Investigator:** JAMES J BIEKER
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $465,752
- **Award type:** 1
- **Project period:** 2020-04-15 → 2024-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9971391

## Citation

> US National Institutes of Health, RePORTER application 9971391, Coordinate regulation of erythroid and macrophage lineages in development by EKLF/KLF1 (1R01DK121671-01A1). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9971391. Licensed CC0.

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