Outside-in integrin signalling regulates haematopoietic stem cell function via Periostin-Itgav axis.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 27905395.
- Also identified by DOI 10.1038/ncomms13500 and PMC identifier 5146274.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
Abstract
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<sup>-/-</sup> mice recover faster from radiation injury with concomitant loss of primitive HSCs. HSCs from Postn<sup>-/-</sup> 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<sup>-/-</sup> 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.
Medical subject headings
- Cell Adhesion Molecules
- Hematopoietic Stem Cells
- Integrin alphaV
- Signal Transduction