Outside-in integrin signalling regulates haematopoietic stem cell function via Periostin-Itgav axis
Copyright policy )Outside-in integrin signalling regulates haematopoietic stem cell function via Periostin-Itgav axis
AbstractIntegrins 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.
- École Polytechnique Fédérale de Lausanne EPFL Switzerland
- KU Leuven Belgium
- Benaroya Research Institute United States
- Katholieke Universiteit Leuven Belgium
Integrases, Science, Q, Bone Marrow Cells, Integrin alphaV, Hematopoietic Stem Cells, Models, Biological, Article, Mice, Phosphatidylinositol 3-Kinases, Animals, Myeloid Cells, Cell Adhesion Molecules, Proto-Oncogene Proteins c-akt, Cells, Cultured, Cyclin-Dependent Kinase Inhibitor p27, Cell Proliferation, DNA Damage, Phosphoinositide-3 Kinase Inhibitors, Protein Binding, Signal Transduction
Integrases, Science, Q, Bone Marrow Cells, Integrin alphaV, Hematopoietic Stem Cells, Models, Biological, Article, Mice, Phosphatidylinositol 3-Kinases, Animals, Myeloid Cells, Cell Adhesion Molecules, Proto-Oncogene Proteins c-akt, Cells, Cultured, Cyclin-Dependent Kinase Inhibitor p27, Cell Proliferation, DNA Damage, Phosphoinositide-3 Kinase Inhibitors, Protein Binding, Signal Transduction
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