Molecular Characterization of Prospectively Isolated Multipotent Mesenchymal Progenitors Provides New Insight into the Cellular Identity of Mesenchymal Stem Cells in Mouse Bone Marrow

Abstract

Despite great progress in the identification of mesenchymal stem cells (MSCs) from bone marrow (BM), our knowledge of their in vivo cellular identity remains limited. We report here that cells expressing the transcription factor Ebf2 in adult BM display characteristics of MSCs. The Ebf2⁺ cells are highly clonal and physiologically quiescent. In vivo lineage-tracing experiments, single cell clone transplantations, and in vitro differentiation assays revealed their self-renewal and multilineage differentiation capacity. Gene expression analysis of the freshly sorted Ebf2⁺ cells demonstrated the expression of genes previously reported to be associated with MSCs and the coexpression of multiple lineage-associated genes at the single-cell level. Thus, Ebf2 expression is not restricted to committed osteoblast progenitor cells but rather marks a multipotent mesenchymal progenitor cell population in adult mouse BM. These cells do not appear to completely overlap the previously reported MSC populations. These findings provide new insights into the in vivo cellular identity and molecular properties of BM mesenchymal stem and progenitor cells.

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SUPPLEMENTAL MATERIAL

Supplemental material for this article may be found at http://dx.doi.org/10.1128/MCB.01287-12.

ACKNOWLEDGMENTS

We thank Liselotte Lenner in Linköping University in Sweden and Marta Florio San Raffaele Scientific Institute, Milan, Italy, for valuable advice and technical assistance.

This study was supported by the postdoctoral fellowship from the Swedish Research Council (K2008-77PK-20879-01-2) and the Cancerfonden (CAN 2009/1589). This study was also supported by running grants from the Swedish Research Council (2009-2675), the Cancerfonden (CAN 2012-2015), AFA Insurance Regenerative Medicine Program, and the Faculty of Medicine at Linköping University.

H.Q. designed research, performed research, collected data, analyzed and interpreted data, performed statistical analysis, and wrote the manuscript. M.S. designed research, analyzed and interpreted data, and wrote the manuscript. N.P. contributed to the differentiation experiments, and K.N. contributed to the histology. J.S. established the Ebf2 reporter transgenic mouse breeding. F.C., A.B., and G.G.C. designed, generated, and validated the Ebf2-CreER^T2 transgenic line.