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2992 Role of β7 Integrin in Hematopoietic Stem Cell Trafficking

Program: Oral and Poster Abstracts
Session: 701. Experimental Transplantation - Basic Biology, Engraftment and Disease Activity: Poster II
Sunday, December 9, 2012, 6:00 PM-8:00 PM
Hall B1-B2, Level 1, Building B (Georgia World Congress Center)

Jodi Murakami1*, Baohui Xu2*, Christopher B. Franco2,3*, Stephen J. Galli2,4*, Irving L. Weissman, MD2,3 and Ching-Cheng Chen1

1Division of Hematopoietic Stem Cell & Leukemia Research, Beckman Research Institute, City of Hope, Duarte, CA
2Department of Pathology, Stanford University School of Medicine, Stanford, CA
3Institute of Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, CA
4Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, CA

β7 integrin (β7), a well studied integrin chain, associates with either the α4 or αE chains to form a heterodimer on the cell surface.  While it plays a key role in the migratory activities of hematopoietic progenitors and mature effector cells in the periphery, the overall importance of β7 in adult hematopoiesis remains controversial.  We have recently identified a small subpopulation of hematopoietic stem cells (HSCs) in the bone marrow (BM) that express β7 integrin at steady state. These β7+ HSCs are capable of long-term reconstitution of both the lymphoid and myeloid compartments, ruling out the possibility that β7 expression on HSCs constitutes a marker for a homogeneous lineage-restricted progenitor population.  We also found that these β7+ HSCs have an inherent advantage over β7- HSCs in competitive reconstitution assays.  Loss of β7 results in the retention of HSCs in the BM and reduced HSC reconstitution potential.  Quantitative real-time PCR revealed that β7 deficient HSCs downregulated the chemokine receptor Cxcr4.  Furthermore, blockade of the α4β7 integrin ligand, mucosal addressin cell adhesion molecule 1 (MAdCAM-1), exhibits a similar phenotype in HSC retention and competitive reconstitution.  Interestingly, we discovered that β7 deficient mice have enhanced survival and faster hematopoietic recovery after 5-fluorouracil-induced myeloablative stress, indicating that the decreased engraftment of β7 deficient HSCs may not due to a functional defect, but rather is more likely caused by impaired homing capabilities.  Taken together, these data strongly suggest that β7 integrin is essential for HSC homing during the transplantation process.

Disclosures: No relevant conflicts of interest to declare.

*signifies non-member of ASH