A mechanosensitive peri-arteriolar niche for osteogenesis and lymphopoiesis

Nature. 2021 Mar;591(7850):438-444. doi: 10.1038/s41586-021-03298-5. Epub 2021 Feb 24.

Abstract

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 progenitors1-6. LEPR+ cells are heterogeneous, including skeletal stem cells and osteogenic and adipogenic progenitors7-12, 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, osteolectin13,14, 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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adipose Tissue / cytology
  • Aging
  • Animals
  • Arterioles*
  • Bone Marrow Cells / cytology
  • Bone and Bones / cytology
  • Female
  • Hematopoietic Cell Growth Factors / metabolism
  • Lectins, C-Type / metabolism
  • Lymphocytes / cytology
  • Lymphopoiesis*
  • Male
  • Mice
  • Osteogenesis*
  • Receptors, Leptin / metabolism
  • Stem Cell Factor
  • Stem Cell Niche*
  • Stromal Cells / cytology

Substances

  • Clec11A protein, mouse
  • Hematopoietic Cell Growth Factors
  • Lectins, C-Type
  • Receptors, Leptin
  • Stem Cell Factor
  • leptin receptor, mouse