Osterix Marks Distinct Waves of Primitive and Definitive Stromal Progenitors during Bone Marrow Development

• Published in: Developmental cell Vol. 29; no. 3; pp. 340 - 349
• Main Authors: Mizoguchi, Toshihide, Pinho, Sandra, Ahmed, Jalal, Kunisaki, Yuya, Hanoun, Maher, Mendelson, Avital, Ono, Noriaki, Kronenberg, Henry M., Frenette, Paul S.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 12.05.2014
• Subjects: Adipocytes - cytology; Animals; Bone and Bones - embryology; Bone Marrow - embryology; Bone Marrow Cells - metabolism; Bone Regeneration - physiology; Bone Regeneration - radiation effects; Cell Lineage; Mesenchymal Stromal Cells - metabolism; Mice; Mice, Inbred C57BL; Mice, Transgenic; Nestin - metabolism; Osteoblasts - metabolism; Sp7 Transcription Factor; Transcription Factors - metabolism
• ISSN: 1534-5807; 1878-1551; 1878-1551
• DOI: 10.1016/j.devcel.2014.03.013

Mesenchymal stem and progenitor cells (MSPCs) contribute to bone marrow (BM) homeostasis by generating multiple types of stromal cells. MSPCs can be labeled in the adult BM by Nestin-GFP, whereas committed osteoblast progenitors are marked by Osterix expression. However, the developmental origin and hierarchical relationship of stromal cells remain largely unknown. Here, by using a lineage-tracing system, we describe three distinct waves of contributions of Osterix+ cells in the BM. First, Osterix+ progenitors in the fetal BM contribute to nascent bone tissues and transient stromal cells that are replaced in the adult marrow. Second, Osterix-expressing cells perinatally contribute to osteolineages and long-lived BM stroma, which have characteristics of Nestin-GFP+ MSPCs. Third, Osterix labeling in the adult marrow is osteolineage-restricted, devoid of stromal contribution. These results uncover a broad expression profile of Osterix and raise the intriguing possibility that distinct waves of stromal cells, primitive and definitive, may organize the developing BM. [Display omitted] •Fetal Osterix+ cells give rise to a primitive stroma that is replaced after birth•Neonatal Osterix+ cells contribute to long-lived, definitive stroma•Neonatal Osterix-derived BM stromal cells mark definitive MSPCs in the adult•Osterix-derived MSPCs contribute to tissue regeneration after injury Bone marrow (BM) mesenchymal stem and progenitor cells (MSPCs) generate multiple types of stromal cells. However, the origin of MSPCs remains unknown. Mizoguchi et al. show that Osterix-expressing cells mark at least three waves of progenitors during BM development and that definitive Nestin+ long-lived stromal progenitors are established during the perinatal stage.