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Åke Borg

Åke Borg

Principal investigator

Åke Borg

Cytohesin 1 regulates homing and engraftment of human hematopoietic stem and progenitor cells

Author

  • Justyna Rak
  • Katie Foster
  • Kasia Potrzebowska
  • Mehrnaz Safaee Talkhoncheh
  • Natsumi Miharada
  • Karolina Komorowska
  • Therese Torngren
  • Anders Kvist
  • Åke Borg
  • Lena Svensson
  • Dominique Bonnet
  • Jonas Larsson
Show all

Summary, in English

Adhesion is a key component of hematopoietic stem cell regulation mediating homing and retention to the niche in the bone marrow. Here, using an RNA interference screen, we identify cytohesin 1 (CYTH1) as a critical mediator of adhesive properties in primary human cord blood-derived hematopoietic stem and progenitor cells (HSPCs). Knockdown of CYTH1 disrupted adhesion of HSPCs to primary human mesenchymal stroma cells. Attachment to fibronectin and ICAM1, 2 integrin ligands, was severely impaired, and CYTH1-deficient cells showed a reduced integrin b1 activation response, suggesting that CYTH1 mediates integrin-dependent functions. Transplantation of CYTH1-knockdown cells to immunodeficient mice resulted in significantly lower long-term engraftment levels, associated with a reduced capacity of the transplanted cells to home to the bone marrow. Intravital microscopy showed that CYTH1 deficiency profoundly affects HSPC mobility and localization within the marrow space and thereby impairs proper lodgment into the niche. Thus, CYTH1 is a novel major regulator of adhesion and engraftment in human HSPCs through mechanisms that, at least in part, involve the activation of integrins.

Department/s

  • StemTherapy: National Initiative on Stem Cells for Regenerative Therapy
  • Division of Molecular Medicine and Gene Therapy
  • Breastcancer-genetics
  • BioCARE: Biomarkers in Cancer Medicine improving Health Care, Education and Innovation
  • Division of Microbiology, Immunology and Glycobiology - MIG

Publishing year

2017-02-23

Language

English

Pages

950-958

Publication/Series

Blood

Volume

129

Issue

8

Document type

Journal article

Publisher

American Society of Hematology

Topic

  • Cell and Molecular Biology

Status

Published

ISBN/ISSN/Other

  • ISSN: 0006-4971