Outside-in integrin signalling regulates haematopoietic stem cell function via Periostin-Itgav axis

Nat Commun. 2016 Dec 1:7:13500. doi: 10.1038/ncomms13500.


Integrins play an important role in haematopoietic stem cell (HSC) maintenance in the bone marrow niche. Here, we demonstrate that Periostin (Postn) via interaction with Integrin-αv (Itgav) regulates HSC proliferation. Systemic deletion of Postn results in peripheral blood (PB) anaemia, myelomonocytosis and lymphopenia, while the number of phenotypic HSCs increases in the bone marrow. Postn-/- mice recover faster from radiation injury with concomitant loss of primitive HSCs. HSCs from Postn-/- mice show accumulation of DNA damage generally associated with aged HSCs. Itgav deletion in the haematopoietic system leads to a similar PB phenotype and HSC-intrinsic repopulation defects. Unaffected by Postn, Vav-Itgav-/- HSCs proliferate faster in vitro, illustrating the importance of Postn-Itgav interaction. Finally, the Postn-Itgav interaction inhibits the FAK/PI3K/AKT pathway in HSCs, leading to increase in p27Kip1 expression resulting in improved maintenance of quiescent HSCs. Together, we demonstrate a role for Itgav-mediated outside-in signalling in regulation of HSC proliferation and stemness.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bone Marrow Cells / cytology
  • Cell Adhesion Molecules / deficiency
  • Cell Adhesion Molecules / metabolism*
  • Cell Proliferation
  • Cells, Cultured
  • Cyclin-Dependent Kinase Inhibitor p27 / metabolism
  • DNA Damage
  • Hematopoietic Stem Cells / cytology
  • Hematopoietic Stem Cells / metabolism*
  • Integrases / metabolism
  • Integrin alphaV / metabolism*
  • Mice
  • Models, Biological
  • Myeloid Cells / metabolism
  • Phosphatidylinositol 3-Kinases / metabolism
  • Phosphoinositide-3 Kinase Inhibitors
  • Protein Binding
  • Proto-Oncogene Proteins c-akt / antagonists & inhibitors
  • Proto-Oncogene Proteins c-akt / metabolism
  • Signal Transduction*


  • Cell Adhesion Molecules
  • Integrin alphaV
  • Phosphoinositide-3 Kinase Inhibitors
  • Postn protein, mouse
  • Cyclin-Dependent Kinase Inhibitor p27
  • Proto-Oncogene Proteins c-akt
  • Cre recombinase
  • Integrases