Meis1 Is Required for Adult Mouse Erythropoiesis, Megakaryopoiesis and Hematopoietic Stem Cell Expansion

Abstract

<div><p><i>Meis1</i> is recognized as an important transcriptional regulator in hematopoietic development and is strongly implicated in the pathogenesis of leukemia, both as a Hox transcription factor co-factor and independently. Despite the emerging recognition of <i>Meis1</i>’s importance in the context of both normal and leukemic hematopoiesis, there is not yet a full understanding of <i>Meis1</i>’s functions and the relevant pathways and genes mediating its functions. Recently, several conditional mouse models for <i>Meis1</i> have been established. These models highlight a critical role for <i>Meis1</i> in adult mouse hematopoietic stem cells (HSCs) and implicate reactive oxygen species (ROS) as a mediator of <i>Meis1</i> function in this compartment. There are, however, several reported differences between these studies in terms of downstream progenitor populations impacted and effectors of function. In this study, we describe further characterization of a conditional knockout model based on mice carrying a loxP-flanked exon 8 of <i>Meis1</i> which we crossed onto the inducible Cre localization/expression strains, B6;129-<i>Gt(ROSA)26Sor</i>^{<i>tm1(Cre/ERT)Nat</i>}/J or B6.Cg-Tg(Mx1-Cre)1Cgn/J. Findings obtained from these two inducible Meis1 knockout models confirm and extend previous reports of the essential role of <i>Meis1</i> in adult HSC maintenance and expansion and provide new evidence that highlights key roles of Meis1 in both megakaryopoiesis and erythropoiesis. Gene expression analyses point to a number of candidate genes involved in Meis1’s role in hematopoiesis. Our data additionally support recent evidence of a role of <i>Meis1</i> in ROS regulation.</p></div