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Blood, 1 October 2007, Vol. 110, No. 7, pp. 2399-2407.
Prepublished online as a Blood First Edition Paper on June 22, 2007; DOI 10.1182/blood-2006-10-051276.


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Submitted October 10, 2006
Accepted June 15, 2007

Distinct roles of integrins {alpha}6 and {alpha}4 in homing of fetal liver hematopoietic stem and progenitor cells

Hong Qian, Elisabeth Georges-Labouesse, Alexander Nystrom, Anna Domogatskaya, Karl Tryggvason, Sten Eirik W Jacobsen, and Marja Ekblom*

Hematopoietic Stem Cell Laboratory, Lund Strategic Center for Stem Cell Biology and Cell Therapy, Lund University, Lund, Sweden
IGBMC, CNRS/INSERM/ULP, Illkirch, France
Department of Cell and Matrix Biology, Lund University, Lund, Sweden
Department of Medical Biochemistry and Biophysics, Karolinska Institute, Stockholm, Sweden
Department of Hematology, Lund University Hosptial, Lund, Sweden

* Corresponding author; email: marja.ekblom{at}med.lu.se.

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 {alpha}6 and {alpha}4 integrin receptors for homing and engraftment of fetal liver (FL) HSCs and hematopoietic progenitor cells (HPCs) to adult BM by using integrin {alpha}6 gene-deleted mice and function-blocking antibodies. Both integrins were ubiquitously expressed in FL Lin-Sca-1+Kit+ (LSK) cells. Deletion of integrin {alpha}6 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 {alpha}6 antibody did not inhibit BM homing of HSCs. In agreement with this, integrin {alpha}6 gene-deleted FL HSCs did not either display any homing or engraftment defect compared to wild-type littermates. In contrast, inhibition of integrin {alpha}4 receptor by a function-blocking antibody virtually abrogated homing of both FL HSCs and HPCs to BM, indicating distinct functions for integrin {alpha}6 and {alpha}4 receptors during homing of fetal HSCs and HPCs.


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