Distinct roles of integrins alpha6 and alpha4 in homing of fetal liver hematopoietic stem and progenitor cells. - CNRS - Centre national de la recherche scientifique Accéder directement au contenu
Article Dans Une Revue Blood Année : 2007

Distinct roles of integrins alpha6 and alpha4 in homing of fetal liver hematopoietic stem and progenitor cells.

Hong Qian
  • Fonction : Auteur
Alexander Nyström
  • Fonction : Auteur
Anna Domogatskaya
  • Fonction : Auteur
Karl Tryggvason
  • Fonction : Auteur
Sten Eirik W Jacobsen
  • Fonction : Auteur
Marja Ekblom
  • Fonction : Auteur

Résumé

Homing of hematopoietic stem cells (HSCs) into the bone marrow (BM) is a prerequisite for establishment of hematopoiesis during development and following transplantation. However, the molecular interactions that control homing of HSCs, in particular, of fetal HSCs, are not well understood. Herein, we studied the role of the alpha6 and alpha4 integrin receptors for homing and engraftment of fetal liver (FL) HSCs and hematopoietic progenitor cells (HPCs) to adult BM by using integrin alpha6 gene-deleted mice and function-blocking antibodies. Both integrins were ubiquitously expressed in FL Lin(-)Sca-1(+)Kit(+) (LSK) cells. Deletion of integrin alpha6 receptor or inhibition by a function-blocking antibody inhibited FL LSK cell adhesion to its extracellular ligands, laminins-411 and -511 in vitro, and significantly reduced homing of HPCs to BM. In contrast, the anti-integrin alpha6 antibody did not inhibit BM homing of HSCs. In agreement with this, integrin alpha6 gene-deleted FL HSCs did not display any homing or engraftment defect compared with wild-type littermates. In contrast, inhibition of integrin alpha4 receptor by a function-blocking antibody virtually abrogated homing of both FL HSCs and HPCs to BM, indicating distinct functions for integrin alpha6 and alpha4 receptors during homing of fetal HSCs and HPCs.

Dates et versions

hal-00188849 , version 1 (19-11-2007)

Identifiants

Citer

Hong Qian, Elisabeth Georges-Labouesse, Alexander Nyström, Anna Domogatskaya, Karl Tryggvason, et al.. Distinct roles of integrins alpha6 and alpha4 in homing of fetal liver hematopoietic stem and progenitor cells.. Blood, 2007, 110 (7), pp.2399-407. ⟨10.1182/blood-2006-10-051276⟩. ⟨hal-00188849⟩
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