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

Rak, Justyna LU ; Foster, Katie ; Potrzebowska, Kasia LU ; Safaee Talkhoncheh, Mehrnaz LU ; Miharada, Natsumi LU ; Komorowska, Karolina LU ; Torngren, Therese LU ; Kvist, Anders LU orcid ; Borg, Åke LU and Svensson, Lena LU , et al. (2017) In Blood 129(8). p.950-958
Abstract

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... (More)

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.

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organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Blood
volume
129
issue
8
pages
9 pages
publisher
American Society of Hematology
external identifiers
  • pmid:27899358
  • wos:000397020700008
  • scopus:85014938728
ISSN
0006-4971
DOI
10.1182/blood-2016-06-720649
language
English
LU publication?
yes
id
718e9a5d-26bd-4e9d-81fc-58d4d535be81
alternative location
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5335807/
date added to LUP
2017-04-11 16:13:47
date last changed
2025-01-20 12:52:12
@article{718e9a5d-26bd-4e9d-81fc-58d4d535be81,
  abstract     = {{<p>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.</p>}},
  author       = {{Rak, Justyna and Foster, Katie and Potrzebowska, Kasia and Safaee Talkhoncheh, Mehrnaz and Miharada, Natsumi and Komorowska, Karolina and Torngren, Therese and Kvist, Anders and Borg, Åke and Svensson, Lena and Bonnet, Dominique and Larsson, Jonas}},
  issn         = {{0006-4971}},
  language     = {{eng}},
  month        = {{02}},
  number       = {{8}},
  pages        = {{950--958}},
  publisher    = {{American Society of Hematology}},
  series       = {{Blood}},
  title        = {{Cytohesin 1 regulates homing and engraftment of human hematopoietic stem and progenitor cells}},
  url          = {{http://dx.doi.org/10.1182/blood-2016-06-720649}},
  doi          = {{10.1182/blood-2016-06-720649}},
  volume       = {{129}},
  year         = {{2017}},
}