Characterization of a novel hematopoietic marker expressed from early embryonic hematopoietic stem cells to adult mature lineages.
A novel membrane protein has been identified in the course of screening for differentially expressed cDNAs in human embryonic hematopoietic sites. This 37- to 38-kDa molecule, designated KLIP-1 (killer lineage protein), consisting of 350 amino acids and containing five transmembrane domains, is encoded by the 5093-bp KLIP-1 gene, composed of nine exons and located on chromosome 6 (6p21.1-6p21.2). We found the KLIP-1 protein to be expressed by nucleated hematopoietic cells, from early embryonic hematopoietic stem cells through mature adult blood lymphoid lineages, either as membrane or as cytoplasmic molecules. In day-30/32 human embryo sections, KLIP-1 protein expression is restricted to circulating hematopoietic cells at hematopoiesis sites. Membrane KLIP-1 is expressed by fetal and adult GP-A(+) erythroblasts, the fetal liver CD34(+) subset, fetal spleen, and adult bone marrow CD56(+) NK and CD19(+) B cells. Among mature blood cells, surface KLIP-1 expression is restricted to CD56(+) NK cells, indicating KLIP-1 to be a novel marker of this population. Altogether, these results indicate that membrane export of KLIP-1 antigen is developmentally and ontogenetically regulated. The high degree of conservation of the KLIP-1 protein sequence among mammals strongly suggests that it plays an important role during hematopoiesis and may exercise similar functions in human and mouse blood cells. The KLIP-1 molecule may therefore constitute a powerful tool for improving knowledge of both human hematopoiesis and NK cell ontogeny and immune functions.
Prost
Stéphane
S
Commissariat à l'Energie Atomique, Direction des Sciences du Vivant, Département de Recherche Médicale Service de Neurovirologie, Fontenay aux Roses, France.
LeDiscorde
Magali
M
Haddad
Rima
R
Gluckman
Jean-Claude
JC
Canque
Bruno
B
Kirszenbaum
Marek
M
D000328:Adult; D000595:Amino Acid Sequence; D000818:Animals; D018952:Antigens, CD34; D015415:Biomarkers; D019070:Cell Lineage; D002874:Chromosome Mapping; D004622:Embryo, Mammalian / Q000737:chemistry / Q000166:cytology*; D020869:Gene Expression Profiling; D018507:Gene Expression Regulation, Developmental; D006410:Hematopoiesis; D006412:Hematopoietic Stem Cells / Q000166:cytology*; D006801:Humans; D008565:Membrane Proteins / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D008969:Molecular Sequence Data; D014018:Tissue Distribution
D018952:Antigens, CD34; D015415:Biomarkers; D008565:Membrane Proteins; C478651:YIPF3 protein, human