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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
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

Abstract 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.

Keywords

  • Cell and Molecular Biology

Other

Published
  • ISSN: 0006-4971
Åke Borg
Åke Borg
E-mail: ake.borg [at] med.lu.se

Principal investigator

Oncology and Pathology, MV

+46 46 275 25 52

MV 404 C21B2

90

Project manager

Familial Breast Cancer

90

Professor

Oncology and Pathology, MV

MV 404 C21C2

90