# Murine hematopoietic progenitor cell lines with erythroid and megakaryocyte potential

## TL;DR

Scientists created a system to expand and study red blood cell and platelet progenitor cells in mice, enabling research on blood cell development and human diseases.

## Contribution

A novel system using Hoxa7 to expand and differentiate murine megakaryocyte-erythroid progenitor cells in vitro and in vivo.

## Key findings

- Hoxa7-TPO cells resemble and differentiate into megakaryocyte-erythroid progenitors upon Hoxa7 inactivation.
- Genetic studies in Hoxa7-TPO cells recapitulate the roles of Klf1 and Nfe2 in blood cell development.
- Disruption of Gp1ba in Hoxa7-TPO cells models human Bernard-Soulier syndrome features.

## Abstract

Red blood cells and platelets derive from bi-potential bone marrow megakaryocyte-erythroid progenitors, but their study is constrained by cell scarcity and limited experimental systems. Here we show that conditional expression of a virally transduced, regulated form of Hoxa7 enables expansion of murine cells resembling megakaryocyte-erythroid progenitors (Hoxa7-TPO), which undergo erythro-megakaryocytic differentiation upon Hoxa7 inactivation. The close relationship of Hoxa7-TPO cells to megakaryocyte-erythroid progenitors is supported by genetic and phenotypic analyses, and mature Hoxa7-TPO-derived red blood cells and platelets are largely indistinguishable from their primary counterparts. Genetic knock-out studies in Hoxa7-TPO cells recapitulate the key function of Klf1 and Nfe2 in red blood cell and platelet development, respectively, while disruption of the von Willebrand receptor gene Gp1ba recapitulates features of human Bernard-Soulier syndrome. Hence, we developed a versatile experimental system for expansion and differentiation of megakaryocyte-erythroid progenitors to study red blood cell and platelet development and model human diseases.

This study presents an experimental system to conditionally immortalize murine megakaryocyte-erythroid progenitor cells, providing a versatile system for investigation of red blood cell and platelet biology in vitro and in vivo.