title: A Role for MOSPD1 in Mesenchymal Stem Cell Proliferation and Differentiation.
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.
authors.affiliation: MRC Centre for Regenerative Medicine, Edinburgh, UK.
authors.forename: Madina
authors.initials: M
authors.lastname: Kara
authors.affiliation: MRC Centre for Regenerative Medicine, Edinburgh, UK.
authors.forename: Richard A
authors.initials: RA
authors.lastname: Axton
authors.affiliation: MRC Centre for Regenerative Medicine, Edinburgh, UK.
authors.forename: Melany
authors.initials: M
authors.lastname: Jackson
authors.affiliation: MRC Centre for Regenerative Medicine, Edinburgh, UK.
authors.forename: Sahar
authors.initials: S
authors.lastname: Ghaffari
authors.affiliation: MRC Centre for Regenerative Medicine, Edinburgh, UK.
authors.forename: Katrin
authors.initials: K
authors.lastname: Buerger
authors.affiliation: MRC Centre for Regenerative Medicine, Edinburgh, UK.
authors.forename: Alistair J
authors.initials: AJ
authors.lastname: Watt
authors.affiliation: MRC Centre for Regenerative Medicine, Edinburgh, UK.
authors.forename: A Helen
authors.initials: AH
authors.lastname: Taylor
authors.affiliation: MRC Centre for Regenerative Medicine, Edinburgh, UK.
authors.forename: Brigid
authors.initials: B
authors.lastname: Orr
authors.affiliation: Orthopaedic Hospital Research Center, University of California at Los Angeles, Los Angeles, California, USA.
authors.forename: Winters R
authors.initials: WR
authors.lastname: Hardy
authors.affiliation: MRC Centre for Regenerative Medicine, Edinburgh, UK.|Orthopaedic Hospital Research Center, University of California at Los Angeles, Los Angeles, California, USA.
authors.forename: Bruno
authors.initials: B
authors.lastname: Peault
authors.affiliation: MRC Centre for Regenerative Medicine, Edinburgh, UK.
authors.forename: Lesley M
authors.initials: LM
authors.lastname: Forrester
mesh_terms: D017667:Adipocytes / Q000378:metabolism; D001853:Bone Marrow / Q000378:metabolism; D002454:Cell Differentiation / Q000235:genetics*; D019070:Cell Lineage / Q000235:genetics; D049109:Cell Proliferation / Q000235:genetics*; D053595:Embryonic Stem Cells / Q000378:metabolism; D058750:Epithelial-Mesenchymal Transition / Q000235:genetics*; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins / Q000235:genetics*; D059630:Mesenchymal Stem Cells; D010006:Osteoblasts / Q000378:metabolism; D012333:RNA, Messenger / Q000096:biosynthesis
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; C000608750:MOSPD1 protein, human; D008565:Membrane Proteins; D012333:RNA, Messenger
keywords: Differentiation; Embryonic stem cells; MOSPD1; Mesenchymal stem cells; Proliferation