JAM-A is highly expressed on human hematopoietic repopulating cells and associates with the key hematopoietic chemokine receptor CXCR4

Chao-Hui Chang, Sarah Hale, Charlotte V Cox, Allison Blair, Barbara Kronsteiner, Rita Grabowska, Youyi Zhang, David Cook, Cheen Khoo, Jack Schrader, Suranahi Buglass Kabuga, Enca Martin-Rendon, Suzanne Watt

Research output: Contribution to journalArticle (Academic Journal)peer-review

16 Citations (Scopus)
310 Downloads (Pure)

Abstract

Hematopoietic stem/progenitor cells (HSPCs) reside in specialized bone marrow microenvironmental niches, with vascular elements (endothelial/mesenchymal stromal cells) and CXCR4-CXCL12 interactions playing particularly important roles for HSPC entry, retention and maintenance. The functional effects of CXCL12 are dependent on its local concentration and rely on complex HSPCniche interactions. Two Junctional Adhesion Molecule family proteins, JAM-B and JAM-C, are reported to mediate HSPC-stromal cell interactions, which in turn regulate CXCL12 production by mesenchymal stromal cells (MSCs). Here, we demonstrate that another JAM family member, JAM-A, is most highly expressed on human hematopoietic stem cells with in vivo repopulating activity. JAM-A blockade, silencing and overexpression show that JAM-A contributes significantly to the adhesion of human HSPCs to IL-1β activated human bone marrow sinusoidal endothelium. Further studies highlight a novel association of JAM-A with CXCR4, with these molecules moving to the leading edge of the cell upon presentation with CXCL12. Therefore, we hypothesize that JAM family members differentially regulate CXCR4 function and CXCL12 secretion in the bone marrow niche
Original languageEnglish
Pages (from-to)1664-1678
Number of pages15
JournalStem Cells
Volume34
Issue number6
Early online date11 Feb 2016
DOIs
Publication statusPublished - Jun 2016

Keywords

  • JAM-A
  • CXCL12
  • CXCR4
  • vascular niche
  • hematopoietic stem/progenitor cells
  • NSG transplants

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