Endochondral ossification is required for hematopoietic stem cell niche formation

Little is known about the formation of niches, local micro-environments required for stem cell maintenance. Here we develop an in vivo assay for adult hematopoietic stem cell (HSC) niche formation 1-2. With this assay, we identified a population of progenitor cells with surface markers CD45(-)Tie2(-)α(V)(+)CD105(+)Thy1.1(-) (CD105(+)Thy1(-)) that when sorted from 15.5 dpc fetal bones (fb) and transplanted under the adult mouse kidney capsule could recruit host-derived blood vessels, produce donor-derived ectopic bones through a cartilage intermediate, and generate a marrow cavity populated by host-derived long term reconstituting HSC (LT-HSC). In contrast, CD45(-)Tie2(-)α(V)(+)CD105(+)Thy1(+) (CD105(+)Thy1(+)) fb progenitors form bone that does not contain a marrow cavity. Suppressing expression of factors involved in endochondral ossification, such as osterix and VEGF, inhibited niche generation 22-24. CD105(+)Thy1(-)progenitor populations derived from regions of the fetal mandible or calvaria that do not undergo endochondral ossification formed only bone without marrow in our assay27. Collectively, our data implicates endochondral ossification, bone formation that proceeds through a cartilage intermediate, as a requirement for adult HSC niche formation.