# miR-223 regulates endothelial to hematopoietic transition

> **NIH NIH R01** · YALE UNIVERSITY · 2022 · $692,264

## Abstract

ABSTRACT
Self-renewing, multipotent hematopoietic stem and progenitor cells (HSPCs) are essential for the foundation and
lifetime maintenance of the adult blood system. Definitive HSPCs are born during embryonic development when a
subset of vascular endothelial cells (ECs), called hemogenic endothelium (hemECs), acquire hematopoietic
potential and give rise to HSPC that bud from the ventral wall of the dorsal aorta. Unfortunately, the regulators
of hemogenic endothelial cell specification and HSPC formation from endothelium are largely undefined.
Recently, we identified miR-223 as novel regulator of hemogenic endothelial cells in zebrafish. Zebrafish and
mice miR-223 mutant embryos had an increased number hemogenic endothelial cells, resulting in mature HSPC
expansion from the onset and into later stages of hematopoiesis. While our studies establish miR-223 as a novel
regulatory factor of hemogenic endothelial cell development and HSPC generation, the specific cellular events
and direct molecular targets regulated by miR-223 in these processes remain unknown. Transcriptome analysis
of wild type and miR-223 mutant endothelial cells from zebrafish and mouse embryos, at stages when definitive
hematopoiesis is occurring, revealed that miR-223 target-genes were enriched for genes relating to protein N-
glycosylation. Interestingly, miRNAs are known to target glycosylation enzymes in processes analogous to EHT,
such as endothelial-to-mesenchymal transition and cancer metastasis. However, whether miRNA-dependent
glycosylation regulation extends to EHT and HSPC induction remains uninvestigated. Here, we will test the
hypothesis that miR-223 fine tunes N-glycosylation levels to control endothelial to hematopoietic cell fate
transition.

## Key facts

- **NIH application ID:** 10348182
- **Project number:** 5R01DK118728-03
- **Recipient organization:** YALE UNIVERSITY
- **Principal Investigator:** Karen Kemper Hirschi
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $692,264
- **Award type:** 5
- **Project period:** 2020-04-15 → 2024-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10348182

## Citation

> US National Institutes of Health, RePORTER application 10348182, miR-223 regulates endothelial to hematopoietic transition (5R01DK118728-03). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10348182. Licensed CC0.

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