1005 - THE IDENTIFICATION OF A PERI-ARTERIOLAR NICHE FOR LYMPHOID PROGENITORS AND OSTEOGENIC PROGENITORS IN THE BONE MARROW

Abstract

Leptin Receptor-expressing (LepR+) stromal cells in adult bone marrow are highly enriched for skeletal stem cells and are the main source of osteoblasts and adipocytes in addition to SCF and Cxcl12 for HSC maintenance (Nature 481:457; Nature 495:231; Cell Stem Cell 15:154). We discovered that a subset of these cells produce a previously uncharacterized bone-forming growth factor, Clec11a/Osteolectin, which promotes the osteogenic differentiation of LepR+ cells and is required for the maintenance of adult skeletal bone mass (eLife 5:e18782). Osteolectin promotes osteogenic differentiation by binding to a11b1 integrin and promoting Wnt pathway activation (eLife 8:e42274). To test if Osteolectin expression could help resolve some of the heterogeneity among LepR+ cells in vivo, we generated a knock-in tdTomato reporter. We found that Osteolectin was exclusively expressed by peri-arteriolar LepR+ cells. The Osteolectin+ cells expressed osteogenic genes while the Osteolectin− cells expressed adipogenic genes. Fate mapping showed that the Osteolectin+ cells gave rise to osteoblasts but not adipocytes in vivo. Conditional deletion of Scf in Osteolectin+ cells did not affect the frequency or function of hematopoietic stem cells (HSCs) or most restricted hematopoietic progenitors in the bone marrow, consistent with our observation that most HSCs and restricted progenitors are associated with sinusoidal blood vessels (Nature 526:126; Cell Stem Cell 24:477); however, common lymphoid progenitors were depleted. This suggests the existence of a peri-arteriolar niche for a subset of lymphoid progenitors in the bone marrow. HSCs are maintained primarily in peri-sinusoidal niches while lymphoid progenitors are maintained in peri-arteriolar and endosteal niches.