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

Forskningsoutput: TidskriftsbidragArtikel i vetenskaplig tidskrift

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 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.

Detaljer

Författare
Enheter & grupper
Externa organisationer
  • Francis Crick Institute
Forskningsområden

Ämnesklassifikation (UKÄ) – OBLIGATORISK

  • Cell- och molekylärbiologi
Originalspråkengelska
Sidor (från-till)950-958
Antal sidor9
TidskriftBlood
Volym129
Utgivningsnummer8
StatusPublished - 2017 feb 23
PublikationskategoriForskning
Peer review utfördJa

Relaterad forskningsoutput

Mehrnaz Safaee Talkhoncheh, 2019, Lund: Lund University, Faculty of Medicine. 100 s.

Forskningsoutput: AvhandlingDoktorsavhandling (sammanläggning)

Komorowska, K., 2018, Lund: Lund University, Faculty of Medicine. 100 s.

Forskningsoutput: AvhandlingDoktorsavhandling (sammanläggning)

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