Mysm1 expression in the bone marrow niche is not essential for hematopoietic maintenance.

Abstract

Myb-Like SWIRM and MPN domains 1 (MYSM1) is a chromatin-binding protein, essential for hematopoietic stem cell (HSC) maintenance and differentiation in humans and mouse models. HSCs in mammalian bone marrow exist in close interactions with many non-hematopoietic cell types in their microenvironment, collectively known as the bone marrow niche. Although cell-intrinsic activities of MYSM1 within the hematopoietic cells are known to play an important role in hematopoietic homeostasis, Mysm1 expression is also widely observed in non-hematopoietic cells, and MYSM1 is implicated as an important regulator of mesenchymal stem cell differentiation, osteoblast function, and adipogenesis within the bone marrow. In this work we for the first time test the roles of Mysm1 within the non-hematopoietic cells of the bone marrow niche in the maintenance of HSCs and hematopoietic homeostasis. For this purpose, wild-type mouse bone marrow was transplanted into Mysm1fl/flTg.CreERT2 recipient mice, followed by tamoxifen-induced ablation of Mysm1 specifically within the non-hematopoietic cells of the recipient. HSC functions and hematopoiesis in these chimeras, with wild-type HSCs and a Mysm1-deficient bone marrow environment, are characterized in the current work. We report that the selective deletion of Mysm1 in non-hematopoietic cells did not affect HSC maintenance and differentiation, with the mice maintaining the normal number and viability of HSCs, diverse hematopoietic progenitors, and mature hematopoietic and immune cell types. Overall we conclude that Mysm1 expression within the niche is not essential for the maintenance of hematopoietic homeostasis.