Unknown,Transcriptomics,Genomics,Proteomics

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CD146 expression in mesenchymal stem cells is associated with vascular smooth muscle commitment

ABSTRACT: Bone-marrow mesenchymal stem cells (MSCs) are plastic adherent cells that can differentiate into various tissue lineages, including osteoblasts, adipocytes and chondrocytes. However, this progenitor property is not shared by all cells within the MSC population. In addition, MSCs vary in their proliferation capacities and expression of markers. Because of heterogeneity of CD146 expression in the MSC population, we compared CD146-/Low and CD146High cells under clonal and non-clonal (sorted MSCs) conditions to determine whether this expression is associated with specific functions. CD146-/Low and CD146High MSCs did not differ in colony-forming unit-fibroblast number, osteogenic and adipogenic differentiation or in vitro hematopoietic supportive activity. However, CD146-/Low clones proliferated slightly but significantly faster than did CD146High clones. In addition, a strong expression of CD146 molecule was associated with a commitment towards a vascular smooth muscle cell lineage with upregulation of calponin-1 expression. Thus, within a bone-marrow MSC population, certain subpopulations characterized by high expression of CD146, are committed toward a vascular smooth muscle cell lineage. Clonal MSC were selected on the basis of CD146 level at their surface (CD146Low and CD146 High) and non-clonal MSC were compared from 4 different donors.

ORGANISM(S): Homo sapiens

SUBMITTER: Nicolas Espagnolle

PROVIDER: E-GEOD-48540 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Project description:A widely shared view reads that 'MSCs' are ubiquitous in human connective tissues, can be defined by a common in vitro phenotype, share a skeletogenic potential as assessed by in vitro differentiation assays, and coincide with the ubiquitous 'pericytes.' Using stringent in vivo differentiation assays and transcriptome analysis, we show here that human cell populations from different anatomical sources, which would all be regarded as 'MSCs' based on these criteria and assumptions, actually differ widely in their transcriptomic signature and in vivo differentiation potential. In contrast, they share the capacity to guide the assembly of functional microvessels in vivo, regardless of their anatomical source, or in situ identity as perivascular or circulating cells. This analysis further reveals that muscle 'pericytes,' which are not spontaneously osteo-chondrogenic as previously claimed, may indeed coincide with an ectopic perivascular subset of committed myogenic cells similar to satellite cells. Cord blood-derived stromal cells, on the other hand, display the unique capacity to form cartilage in vivo spontaneously, in addition to an assayable osteogenic capacity. These data suggest the need to revise current misconceptions on the origin and function of so-called 'MSCs,' with important applicative implications. The data also support the view that rather than a uniform class of 'MSCs,' different mesoderm derivatives include distinct classes of tissue-specific committed progenitors, likely of different developmental origin. The anatomical identity of 'mesenchymal stem cells', (MSCs) their phenotype, their distribution in the different tissues, their lineage, their physiological functions and biological properties represent one of the most controversial and confusing areas in stem cell biology. The definition of the origin, anatomy, function and biological properties of so-called MSCs has obvious implications both for understanding their biology and for their use in potential therapies. We have previously identified a minimal surface phenotype suited not only to enrich for the archetypal human 'MSCs' in uncultured bone marrow cell suspensions, but also to correlate their ex vivo-assayed clonogenic capacity with their in situ identity and in vivo fate following tranplantation (Sacchetti et al., 2007). Stromal cell strains were established from four different tissue sources: bone marrow (BM), skeletal muscle (MU), periosteum (PE), and perinatal blood-borne cord blood (CB) cells. For all post-natal tissue sources, clonogenic cells were prospectively isolated based on a minimal surface phenotype as previously described for human BMSCs (CD34-/CD45-/CD146+); colonies of CB-derived stromal cells were established as described (Kluth et al., 2010; Kogler et al., 2004). Of note, CD146 identified a clonogenic subset in MU (presented below) and PE (data not shown), as it does in BM. Multi-clonal strains derived from growth of the originally explanted cells were then expanded under identical culture conditions; all resulting cell strains exhibited the canonical in vitro cell surface markers regarded as characteristic of 'MSCs'. In order to characterize the specificity and functional significance of the cell surface phenotype of 'MSCs' that is widely regarded as a defining feature of 'MSCs' across tissues, we performed gene expression profiling using Affimetrix technology.

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CD146 expression in mesenchymal stem cells is associated with vascular smooth muscle commitment

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