Osterix marks distinct waves of primitive and definitive stromal progenitors during bone marrow development

Toshihide Mizoguchi, Sandra Pinho, Jalal Ahmed, Yuya Kunisaki, Maher Hanoun, Avital Mendelson, Noriaki Ono, Henry M. Kronenberg, Paul S. Frenette

Research output: Contribution to journalArticlepeer-review

329 Scopus citations


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.

Original languageEnglish
Pages (from-to)340-349
Number of pages10
JournalDevelopmental Cell
Issue number3
StatePublished - 12 May 2014
Externally publishedYes


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