| First Author | Khurana S | Year | 2016 |
| Journal | Nat Commun | Volume | 7 |
| Pages | 13500 | PubMed ID | 27905395 |
| Mgi Jnum | J:243166 | Mgi Id | MGI:5907796 |
| Doi | 10.1038/ncomms13500 | Citation | Khurana S, et al. (2016) Outside-in integrin signalling regulates haematopoietic stem cell function via Periostin-Itgav axis. Nat Commun 7:13500 |
| abstractText | 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-alphav (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. |
