Distinct roles of integrins α6 and α4 in homing of fetal liver hematopoietic stem and progenitor cells
Open Access
- 1 October 2007
- journal article
- Published by American Society of Hematology in Blood
- Vol. 110 (7), 2399-2407
- https://doi.org/10.1182/blood-2006-10-051276
Abstract
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 α6 and α4 integrin receptors for homing and engraftment of fetal liver (FL) HSCs and hematopoietic progenitor cells (HPCs) to adult BM by using integrin α6 gene–deleted mice and function-blocking antibodies. Both integrins were ubiquitously expressed in FL Lin−Sca-1+Kit+ (LSK) cells. Deletion of integrin α6 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 α6 antibody did not inhibit BM homing of HSCs. In agreement with this, integrin α6 gene–deleted FL HSCs did not display any homing or engraftment defect compared with wild-type littermates. In contrast, inhibition of integrin α4 receptor by a function-blocking antibody virtually abrogated homing of both FL HSCs and HPCs to BM, indicating distinct functions for integrin α6 and α4 receptors during homing of fetal HSCs and HPCs.Keywords
This publication has 65 references indexed in Scilit:
- Hemopoietic stem cell engraftmentExperimental Hematology, 2006
- How do stem cells find their way home?Blood, 2005
- Ex vivo manipulation of umbilical cord blood-derived hematopoietic stem/progenitor cells with recombinant human stem cell factor can up-regulate levels of homing-essential molecules to increase their transmigratory potentialExperimental Hematology, 2003
- Integrins in regulation of tissue development and functionThe Journal of Pathology, 2003
- Biology of Hematopoietic Stem Cells and Progenitors: Implications for Clinical ApplicationAnnual Review of Immunology, 2003
- Fetal and Adult Hematopoietic Stem Cells Require β1 Integrin Function for Colonizing Fetal Liver, Spleen, and Bone MarrowImmunity, 2000
- Functional differences between transplantable human hematopoietic stem cells from fetal liver, cord blood, and adult marrowExperimental Hematology, 1999
- Integrin SignalingScience, 1999
- Impaired migration but not differentiation of haematopoietic stem cells in the absence of β1 integrinsNature, 1996
- Fibronectin and VLA-4 in haematopoietic stem cell–microenvironment interactionsNature, 1991