Differential cytokine contributions of perivascular haematopoietic stem cell niches

Nat Cell Biol. 2017 Mar;19(3):214-223. doi: 10.1038/ncb3475. Epub 2017 Feb 20.


Arterioles and sinusoids of the bone marrow (BM) are accompanied by stromal cells that express nerve/glial antigen 2 (NG2) and leptin receptor (LepR), and constitute specialized niches that regulate quiescence and proliferation of haematopoietic stem cells (HSCs). However, how niche cells differentially regulate HSC functions remains unknown. Here, we show that the effects of cytokines regulating HSC functions are dependent on the producing cell sources. Deletion of chemokine C-X-C motif ligand 12 (Cxcl12) or stem cell factor (Scf) from all perivascular cells marked by nestin-GFP dramatically depleted BM HSCs. Selective Cxcl12 deletion from arteriolar NG2+ cells, but not from sinusoidal LepR+ cells, caused HSC reductions and altered HSC localization in BM. By contrast, deletion of Scf in LepR+ cells, but not NG2+ cells, led to reductions in BM HSC numbers. These results uncover distinct contributions of cytokines derived from perivascular cells in separate vascular niches to HSC maintenance.

Publication types

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

MeSH terms

  • Animals
  • Antigens
  • Arterioles / cytology
  • Bone Marrow / metabolism
  • Cell Count
  • Chemokine CXCL12 / metabolism
  • Cytokines / metabolism*
  • Gene Deletion
  • Green Fluorescent Proteins / metabolism
  • Hematopoietic Stem Cells / cytology*
  • Hematopoietic Stem Cells / metabolism*
  • Imaging, Three-Dimensional
  • Integrases / metabolism
  • Mice, Transgenic
  • Nestin / metabolism
  • Proteoglycans
  • Receptors, Leptin / metabolism
  • Sequence Analysis, RNA
  • Stem Cell Factor / metabolism
  • Stem Cell Niche*


  • Antigens
  • Chemokine CXCL12
  • Cytokines
  • Nestin
  • Proteoglycans
  • Receptors, Leptin
  • Stem Cell Factor
  • chondroitin sulfate proteoglycan 4
  • Green Fluorescent Proteins
  • Cre recombinase
  • Integrases