# Novel Growth Factor Regulators of Early Erythropoieisis

> **NIH NIH R01** · UNIV OF MASSACHUSETTS MED SCH WORCESTER · 2021 · $636,733

## Abstract

Project Summary
Erythropoiesis is the tightly regulated process by which red blood cells are formed from hematopoietic stem
cells. Clinically, the only erythropoiesis-stimulating agents available for the treatment of anemia are the
hormone erythropoietin (Epo), and glucocorticoids, leaving a gap where they are ineffective or contraindicated.
In this inter-disciplinary project, we will use in vivo mouse models of erythropoietic stress, mouse genetics, and
cutting-edge scRNA-Seq approaches to explore a largely uncharted area of non-Epo growth factor signaling
and regulatory mechanisms in early erythroid progenitors. We will specifically focus on a potent new regulator
that we have discovered: the cytokine IL-17, which we found stimulates both human and mouse erythroid
progenitors, acting specifically through its receptor IL-17RA.
We first identified IL17 as a novel erythropoietic regulator by overcoming an important technical challenge in
studying erythropoiesis. Until recently, a major challenge in identifying novel erythropoietic regulators was a
lack of information about the earliest stages of erythroid differentiation from stem cells. Early progenitors could
only be defined retrospectively by their erythroid colony forming potential, namely “burst” forming units and
colony forming units [BFU-e(rythroid) and CFU-e respectively]. FACS-based schemes could enrich for BFU-e/
CFU-e, but not purify them. We have now, for the first time, prospectively isolated distinct early stages of
erythropoiesis, guided by novel single cell RNA sequencing (scRNA-Seq) technology and using FACS. We
found that these newly defined progenitors express multiple growth factor receptors that were not previously
recognized as erythroid regulators, and we identified an erythropoietic regulatory role for the first three such
growth-factor receptors that we tested, including IL-17.
Our project is structured around three aims: we will determine IL-17 pathway components involved in
erythropoietic control, the cell biological and transcriptional responses to IL-17 in erythroid and non-erythroid
blood progenitors, and finally, we will investigate the ability of IL-17RA activation to modulate erythropoiesis in
mice in stress and disease, including anemic conditions. In the process, we will apply scRNA-seq technology
to reveal the dynamic structure of the hematopoietic/erythropoietic hierarchies in physiology, disease and
during stress, and the sensitivity of these stem and progenitor cell hierarchies to IL-17 signaling.

## Key facts

- **NIH application ID:** 10134825
- **Project number:** 5R01HL141402-04
- **Recipient organization:** UNIV OF MASSACHUSETTS MED SCH WORCESTER
- **Principal Investigator:** Allon Moshe Klein
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $636,733
- **Award type:** 5
- **Project period:** 2018-04-15 → 2023-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10134825

## Citation

> US National Institutes of Health, RePORTER application 10134825, Novel Growth Factor Regulators of Early Erythropoieisis (5R01HL141402-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10134825. Licensed CC0.

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