Submitted March 26, 2007
Accepted October 15, 2007
Junctional adhesion molecule-A, JAM-A, is a novel cell surface marker for long-term repopulating hematopoietic stem cells
Yasuyoshi Sugano, Masaki Takeuchi, Ayami Hirata, Hirokazu Matsushita, Toshio Kitamura, Minoru Tanaka, and Atsushi Miyajima*
Institute of Molecular and Cellular Biosciences, University of Tokyo, Tokyo, Japan
Core Research for Evolutionary Science & Technology (CREST), Japan Science and Technology Agency (JST), Kawaguchi, Japan
Institute of Medical Science, University of Tokyo, Tokyo, Japan
* Corresponding author; email: miyajima{at}iam.u-tokyo.ac.jp.
Junctional adhesion molecule-A (JAM-A/JAM-1/F11R) is a cell adhesion molecule expressed in epithelial cells, endothelial cells and also hematopoietic cells such as leukocytes, platelets and erythrocytes. Here we show that JAM-A is expressed at a high level in the enriched hematopoietic stem cell (HSC) fraction, i.e. CD34+ c-Kit+ cells in embryonic day 11.5 (E11.5) aorta-gonod-mesonephros (AGM) and E11.5 fetal liver (FL) as well as c-Kit+ Sca-1+ Lineage- (KSL) cells in E14.5 FL, E18.5FL and adult bone marrow (BM). While the percentage of JAM-A+ cells in those tissues decreases during the development, the expression in HSC fraction is maintained throughout life. Colony forming assays reveal that multi-lineage colony forming activity (CFU-mix) in JAM-A+ cells is higher than that in JAM-A- cells in the enriched HSC fraction in all those tissues. Transplantation assays show that long term reconstituting HSC (LTR-HSC) activity is exclusively in the JAM-A+ population and is highly enriched in the JAM-A+ cells sorted directly from whole BM cells by anti-JAM-A antibody alone. Together these results indicate that JAM-A is expressed on hematopoietic precursors in various hematopoietic tissues and is an excellent marker to isolate LTR-HSC.
