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Mesenchymal stem cells (MSCs) are defined as cells that undergo sustained in vitro growth and are able of giving rise to multiple mesenchymal lineages. Although MSCs are already used in regenerative medicine, little is known about their in vivo behavior and developmental derivation. MSCs are a heterogeneous subset of stromal stem cells isolated from many adult tissues. Previous studies have reported that MSCs can differentiate into both mesodermal and neural lineages through a phenomenon referred to as ‘‘dedifferentiation’’ or ‘‘trans-differentiation’’. Limb mesenchymal cells reportedly originate from the lateral plate mesoderm. An additional origin of MSCs is the neural crest. Here, we prospectively identified paraxial mesoderm-derived MSCs in the bone marrow of adult transgenic mice encoding early mesoderm-specific Mesp1-Cre/Floxed-EGFP. We observed that a small but significant amount of Mesp1 + cells existed in adult bone marrow. Interestingly, the detected EGFP + cells in the bone marrow were mostly present in the haematopoietic cells and EGFP + MSCs differentiated into osteocytes, adipocytes, chondrocytes, neurons, glial cells, and myofibroblasts. No significant differences in the in vitro characteristics were observed between EGFP + and EGFP MSCs from Mesp1-Cre/Floxed-EGFP mice. Our results suggested that MSCs in adult bone marrow have a multi-developmental origin and that a portion of them are derived from Mesp1 + early paraxial mesoderm.

Mesp1+ early paraxial mesodermal cells supply initial bone marrow mesenchymal stem cells capable of differentiating into neural crest lineage cells