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

Satish Khurana (), Sarah Schouteden, Javed K. Manesia, Albert Santamaria-Martínez, Joerg Huelsken, Adam Lacy-Hulbert and Catherine M. Verfaillie
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Satish Khurana: KU Leuven
Sarah Schouteden: KU Leuven
Javed K. Manesia: KU Leuven
Albert Santamaria-Martínez: École Polytechnique Fédérale de Lausanne (EPFL)
Joerg Huelsken: École Polytechnique Fédérale de Lausanne (EPFL)
Adam Lacy-Hulbert: Benaroya Research Institute at Virginia Mason
Catherine M. Verfaillie: KU Leuven

Nature Communications, 2016, vol. 7, issue 1, 1-14

Abstract: 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−/− 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.

Date: 2016
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DOI: 10.1038/ncomms13500

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