The tetraspanin CD9 regulates migration, adhesion, and homing of human cord blood CD34(+) hematopoietic stem and progenitor cells
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AbstractThe stromal cell-derived factor-1 (SDF-1)/chemokine C-X-C receptor 4 (CXCR4) axis plays a critical role in homing and engraftment of hematopoietic stem/progenitor cells (HSCs) during bone marrow transplantation. To investigate the transcriptional regulation provided by this axis, we performed the first differential transcriptome profiling of human cord blood CD34(+) cells in response to short-term exposure to SDF-1 and identified a panel of genes with putative homing functions. We demonstrated that CD9, a member of the tetraspanin family of proteins, was ex-pressed in CD34(+) CD38(+/lo) and CD34(+)CD38(+) cells. CD9 levels were enhanced by SDF-1, which simultaneously down-regulated CXCR4 membrane expression. Using specific inhibitors and activators, we demonstrated that CD9 expression was modulated via CXCR4, G-protein, protein kinase C, phospholipase C, extracellular signal-regulated kinase, and Janus kinase 2 signals. Pretreatment of CD34(+) cells with the anti-CD9 monoclonal antibody ALB6 significantly inhibited SDF-1-mediated transendothelial migration and calcium mobilization, whereas adhesion to fibronectin and endothelial cells was enhanced. Pretreatment of CD34+ cells with ALB6 significantly impaired their homing to bone marrow and spleen of sublethally irradiated NOD/SCID (nonobese diabetic/severe combined immune-deficient) mice. Sorted CD34(+)CD9(+) cells displayed lower bone marrow homing capacity compared with that of total CD34(+) cells. CD9 expression on homed CD34(+) cells was significantly up-regulated in vivo. Our results indicate that CD9 might possess specific functions in HSC homing. (Blood. 2011;117(6): 1840-1850)
All Author(s) ListLeung KT, Chan KYY, Ng PC, Lau TK, Chiu WM, Tsang KS, Li CK, Kong CKL, Li K
Journal nameBlood
Year2011
Month2
Day10
Volume Number117
Issue Number6
PublisherAmerican Society of Hematology
Pages1840 - 1850
ISSN0006-4971
eISSN1528-0020
LanguagesEnglish-United Kingdom
Web of Science Subject CategoriesHematology; HEMATOLOGY

Last updated on 2020-28-10 at 00:26