Other
23 Authors
- Ramesh V,
- Ubellacker JM,
- Nosyreva ED,
- Embree C,
- Liu X,
- Shen B,
- Zhang J,
- Zhao YC,
- Tasdogan A,
- Syeda R,
- Hu Z,
- Murphy MM,
- Zhao Z,
- Hu S,
- Yi Y,
- Jia Y,
- Guela S,
- Du L,
- Ju LA,
- Morrison SJ,
- Kara N,
- Mitchell EC,
- Crane GM
| First Author | Shen B | Year | 2021 |
| Journal | Nature | Volume | 591 |
| Issue | 7850 | Pages | 438-444 |
| PubMed ID | 33627868 | Mgi Jnum | J:334856 |
| Mgi Id | MGI:6710163 | Doi | 10.1038/s41586-021-03298-5 |
| Citation | Shen B, et al. (2021) A mechanosensitive peri-arteriolar niche for osteogenesis and lymphopoiesis. Nature 591(7850):438-444 |
| abstractText | Stromal cells in adult bone marrow that express leptin receptor (LEPR) are a critical source of growth factors, including stem cell factor (SCF), for the maintenance of haematopoietic stem cells and early restricted progenitors(1-6). LEPR(+) cells are heterogeneous, including skeletal stem cells and osteogenic and adipogenic progenitors(7-12), although few markers have been available to distinguish these subsets or to compare their functions. Here we show that expression of an osteogenic growth factor, osteolectin(13,14), distinguishes peri-arteriolar LEPR(+) cells poised to undergo osteogenesis from peri-sinusoidal LEPR(+) cells poised to undergo adipogenesis (but retaining osteogenic potential). Peri-arteriolar LEPR(+)osteolectin(+) cells are rapidly dividing, short-lived osteogenic progenitors that increase in number after fracture and are depleted during ageing. Deletion of Scf from adult osteolectin(+) cells did not affect the maintenance of haematopoietic stem cells or most restricted progenitors but depleted common lymphoid progenitors, impairing lymphopoiesis, bacterial clearance, and survival after acute bacterial infection. Peri-arteriolar osteolectin(+) cell maintenance required mechanical stimulation. Voluntary running increased, whereas hindlimb unloading decreased, the frequencies of peri-arteriolar osteolectin(+) cells and common lymphoid progenitors. Deletion of the mechanosensitive ion channel PIEZO1 from osteolectin(+) cells depleted osteolectin(+) cells and common lymphoid progenitors. These results show that a peri-arteriolar niche for osteogenesis and lymphopoiesis in bone marrow is maintained by mechanical stimulation and depleted during ageing. |
