Dissecting the hierarchy and lineage of mesenchymal stem cells by mouse genetics

Determination of stem cell hierarchy/lineage is indispensable for a better understanding and augmentation of many aspects of medical sciences, including the mechanisms of tissue development and maintenance of tissue homeostasis, as well as disease development. It also has implications in the field of tissue regeneration for medical treatments and disease modeling for drug discovery using iPS technology. Mesenchymal stem cells are multipotent stem cell that can differentiate into various type of cells including osteoblasts, adipocytes, myocytes and chondrocytes. Runt-related transcription factor 2 (Runx2) is an essential transcriptional regulator of osteoblast differentiation. Runx2 deficiency in Prx1+-derived cells (Runx2prx1−/− mice) resulted in defective intramembranous ossification. Double-positive cells for Prx1-GFP and stem cell antigen-1 (Sca1) (Prx1+Sca1+ cells) in the calvaria expressed Runx2 at lower levels and were more homogeneous and primitive as compared with Prx1+Sca1− cells. Our results suggest that osteoblast differentiation in vivo may begin at the Prx1+Sca1+ MSC stage with sequential progression to Prx1+Sca1−cells, then Osx+Prx1−Sca1− osteoblast precursors, which eventually form mature α1(I)-collagen+ osteoblasts.

特別講演要旨（Summary of Special Lecture）