Abstract
Mesenchymal stem cells (MSCs) isolated from many tissues including bone marrow and fat can be expanded in vitro and can differentiate into a range of different cell types such as bone, cartilage, and adipocytes. MSCs can also exhibit immunoregulatory properties when transplanted but, although a number of clinical trials using MSCs are in progress, the molecular mechanisms that control their production, proliferation, and differentiation are poorly understood. We identify MOSPD1 as a new player in this process. We generated MOSPD1‐null embryonic stem cells (ESCs) and demonstrate that they are deficient in their ability to differentiate into a number of cell lineages including osteoblasts, adipocytes, and hematopoietic progenitors. The self‐renewal capacity of MOSPD1‐null ESCs was normal and they exhibited no obvious defects in early germ layer specification nor in epithelial to mesenchymal transition (EMT), indicating that MOSPD1 functions after these key steps in the differentiation process. Mesenchymal stem cell (MSC)‐like cells expressing CD73, CD90, and CD105 were generated from MOSPD1‐null ESCs but their growth rate was significantly impaired implying that MOSPD1 plays a role in MSC proliferation. Phenotypic deficiencies exhibited by MOSPD1‐null ESCs were rescued by exogenous expression of MOSPD1, but not MOSPD3 indicating distinct functional properties of these closely related genes. Our in vitro studies were supported by RNA‐sequencing data that confirmed expression of Mospd1 mRNA in cultured, proliferating perivascular pre‐MSCs isolated from human tissue. This study adds to the growing body of knowledge about the function of this largely uncharacterized protein family and introduces a new player in the control of MSC proliferation and differentiation. Stem Cells 2015;33:3077–3086
Highlights
Mesenchymal stem cells (MSCs) hold great promise for cell therapies because they can be isolated from accessible tissues such as bone marrow and fat and they can be expanded extensively in vitro
Mesenchymal stem cell (MSC)-like cells expressing CD73, CD90, and CD105 were generated from MOSPD1-null embryonic stem cells (ESCs) but their growth rate was significantly impaired implying that MOSPD1 plays a role in MSC proliferation
We noted that expression of the epithelial to mesenchymal transition (EMT) marker genes Snai1, Snai2, and Cdh11 increased during ESC differentiation in a comparable manner in both MOSPD1-null and control ESCs indicating that Mospd1 does not play a role in their regulation
Summary
Mesenchymal stem cells (MSCs) hold great promise for cell therapies because they can be isolated from accessible tissues such as bone marrow and fat and they can be expanded extensively in vitro They can differentiate into bone, cartilage, and adipocytes and are proposed to hold immunotherapeutic properties upon transplantation [1]. Major sperm protein (MSP) domaincontaining proteins belong to a large family, which are found in yeast, plants and throughout the animal kingdom from insects to mammals [4,5,6,7] They appear to have diverse roles in a variety of systems including nematode reproduction, synaptic transmission in the central nervous system in the sea slug and in the human neurodegenerative disease amyotrophic lateral sclerosis (ALS) [7,8,9]. Included in this overarching MSP domain-containing family are the four members of the MOSPD1 group
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