title: Evidence that β7 Integrin Regulates Hematopoietic Stem Cell Homing and Engraftment Through Interaction with MAdCAM-1.
abstract: α4β7 integrin is a cell adhesion receptor that is crucial for the migration of hematopoietic progenitors and mature effector cells in the periphery, but its role in adult hematopoiesis is controversial. We identified a subset of hematopoietic stem cells (HSCs) in the bone marrow (BM) that expressed β7 integrin. These β7(+) HSCs were capable of multilineage, long-term reconstitution and had an inherent competitive advantage over β7(-) HSCs. On the other hand, HSCs that lacked β7 integrin (β7KO) had reduced engraftment potential. Interestingly, quantitative RT-PCR and flow cytometry revealed that β7KO HSCs expressed lower levels of the chemokine receptor CXCR4. Accordingly, β7KO HSCs exhibited impaired migration abilities in vitro and BM homing capabilities in vivo. Lethal irradiation induced expression of the α4β7 integrin ligand-mucosal addressin cell adhesion molecule-1 (MAdCAM-1) on BM endothelial cells. Moreover, blocking MAdCAM-1 reduced the homing of HSCs and impaired the survival of recipient mice. Altogether, these data indicate that β7 integrin, when expressed by HSCs, interacted with its endothelial ligand MAdCAM-1 in the BM microenvironment, thereby promoting HSC homing and engraftment.
authors.affiliation: 1 Division of Hematopoietic Stem Cell and Leukemia Research, Beckman Research Institute of City of Hope , Duarte, California.|2 City of Hope Irell & Manella Graduate School of Biological Sciences , Duarte, California.|3 Gehr Family Center for Leukemia Research at City of Hope , Duarte, California.
authors.forename: Jodi L
authors.initials: JL
authors.lastname: Murakami
authors.affiliation: 4 Department of Surgery, Stanford University School of Medicine , Stanford, California.
authors.forename: Baohui
authors.initials: B
authors.lastname: Xu
authors.affiliation: 5 Department of Pathology, Stanford University School of Medicine , Stanford, California.|6 Institute of Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine , Stanford, California.
authors.forename: Christopher B
authors.initials: CB
authors.lastname: Franco
authors.affiliation: 1 Division of Hematopoietic Stem Cell and Leukemia Research, Beckman Research Institute of City of Hope , Duarte, California.|7 Department of Transfusion Medicine, Xijing Hospital, Fourth Military Medical University , Xi'an, People's Republic of China .
authors.forename: Xingbin
authors.initials: X
authors.lastname: Hu
authors.affiliation: 5 Department of Pathology, Stanford University School of Medicine , Stanford, California.|8 Department of Microbiology and Immunology, Stanford University School of Medicine , Stanford, California.
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Galli
authors.affiliation: 5 Department of Pathology, Stanford University School of Medicine , Stanford, California.|6 Institute of Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine , Stanford, California.
authors.forename: Irving L
authors.initials: IL
authors.lastname: Weissman
authors.affiliation: 1 Division of Hematopoietic Stem Cell and Leukemia Research, Beckman Research Institute of City of Hope , Duarte, California.|2 City of Hope Irell & Manella Graduate School of Biological Sciences , Duarte, California.|3 Gehr Family Center for Leukemia Research at City of Hope , Duarte, California.
authors.forename: Ching-Cheng
authors.initials: CC
authors.lastname: Chen
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology; D015815:Cell Adhesion Molecules / Q000378:metabolism*; D002465:Cell Movement / Q000235:genetics*; D002478:Cells, Cultured; D005260:Female; D006085:Graft Survival / Q000235:genetics*; D018380:Hematopoietic Stem Cell Transplantation; D006412:Hematopoietic Stem Cells / Q000378:metabolism / Q000502:physiology*; D039641:Integrin beta Chains / Q000235:genetics* / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009088:Mucoproteins; D011485:Protein Binding; D055153:Stem Cell Niche / Q000235:genetics
chemical_list: D015815:Cell Adhesion Molecules; D039641:Integrin beta Chains; C489082:Madcam1 protein, mouse; D009088:Mucoproteins; C091368:integrin beta7