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

Author

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  • Satish Khurana

    (KU Leuven
    Present address:School of Biology, Indian Institute of Science Education and Research, Thiruvananthapuram, Kerala 695016, India)

  • Sarah Schouteden

    (KU Leuven)

  • Javed K. Manesia

    (KU Leuven)

  • Albert Santamaria-Martínez

    (École Polytechnique Fédérale de Lausanne (EPFL)
    Present address: University of Fribourg, 1700 Fribourg, Switzerland.)

  • Joerg Huelsken

    (École Polytechnique Fédérale de Lausanne (EPFL))

  • Adam Lacy-Hulbert

    (Benaroya Research Institute at Virginia Mason)

  • Catherine M. Verfaillie

    (KU Leuven)

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.

Suggested Citation

  • Satish Khurana & Sarah Schouteden & Javed K. Manesia & Albert Santamaria-Martínez & Joerg Huelsken & Adam Lacy-Hulbert & Catherine M. Verfaillie, 2016. "Outside-in integrin signalling regulates haematopoietic stem cell function via Periostin-Itgav axis," Nature Communications, Nature, vol. 7(1), pages 1-14, December.
    • Handle: RePEc:nat:natcom:v:7:y:2016:i:1:d:10.1038_ncomms13500
    DOI: 10.1038/ncomms13500
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    1. Mara Martín-Alonso & Sharif Iqbal & Pia M. Vornewald & Håvard T. Lindholm & Mirjam J. Damen & Fernando Martínez & Sigrid Hoel & Alberto Díez-Sánchez & Maarten Altelaar & Pekka Katajisto & Alicia G. Ar, 2021. "Smooth muscle-specific MMP17 (MT4-MMP) regulates the intestinal stem cell niche and regeneration after damage," Nature Communications, Nature, vol. 12(1), pages 1-17, December.

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