Junctional adhesion molecule-A, JAM-A, is a novel cell-surface marker for long-term repopulating hematopoietic stem cells.
Junctional adhesion molecule-A (JAM-A/JAM-1/F11R) is a cell adhesion molecule expressed in epithelial and 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; that is, 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). Although the percentage of JAM-A(+) cells in those tissues decreases during development, the expression in the HSC fraction is maintained throughout life. Colony-forming assays reveal that multilineage colony-forming activity in JAM-A(+) cells is higher than that in JAM-A(-) cells in the enriched HSC fraction in all of 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-HSCs.
Sugano
Yasuyoshi
Y
Institute of Molecular and Cellular Biosciences, University of Tokyo, Tokyo, Japan.
Takeuchi
Masaki
M
Hirata
Ayami
A
Matsushita
Hirokazu
H
Kitamura
Toshio
T
Tanaka
Minoru
M
Miyajima
Atsushi
A
D000818:Animals; D018952:Antigens, CD34 / Q000378:metabolism; D000950:Antigens, Ly / Q000378:metabolism; D015415:Biomarkers; D015815:Cell Adhesion Molecules / Q000235:genetics / Q000378:metabolism*; D019070:Cell Lineage; D002462:Cell Membrane / Q000378:metabolism*; D003114:Colony-Forming Units Assay; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000378:metabolism*; D008565:Membrane Proteins / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D019009:Proto-Oncogene Proteins c-kit / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000235:genetics / Q000378:metabolism*; D013997:Time Factors
D018952:Antigens, CD34; D000950:Antigens, Ly; D015415:Biomarkers; D015815:Cell Adhesion Molecules; C498686:F11r protein, mouse; C074650:Ly6a protein, mouse; D008565:Membrane Proteins; D011956:Receptors, Cell Surface; D019009:Proto-Oncogene Proteins c-kit