Murine hematopoietic progenitor cell lines with erythroid and megakaryocyte potential

Ruiqiong Wu, Faraz Salehi, Vanessa Redecke, Zhijun Ma, Marco Marchetti, David Finkelstein, Peng Xu, Yong Cheng, Kimberly A. Queisser, Aaron C. Petrey, Conroy O. Field, Hyun Sook Ahn, Mortimer Poncz, Mitchell J. Weiss and Hans Häcker ()
Additional contact information
Ruiqiong Wu: St. Jude Children’s Research Hospital
Faraz Salehi: University of Utah School of Medicine
Vanessa Redecke: University of Utah School of Medicine
Zhijun Ma: St. Jude Children’s Research Hospital
Marco Marchetti: University of Utah
David Finkelstein: St. Jude Children’s Research Hospital
Peng Xu: St. Jude Children’s Research Hospital
Yong Cheng: St. Jude Children’s Research Hospital
Kimberly A. Queisser: University of Utah School of Medicine
Aaron C. Petrey: University of Utah School of Medicine
Conroy O. Field: Children’s Hospital of Philadelphia
Hyun Sook Ahn: Children’s Hospital of Philadelphia
Mortimer Poncz: Children’s Hospital of Philadelphia
Mitchell J. Weiss: St. Jude Children’s Research Hospital
Hans Häcker: University of Utah School of Medicine

Nature Communications, 2025, vol. 16, issue 1, 1-16

Abstract: 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.

Date: 2025
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DOI: 10.1038/s41467-025-62668-z

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