Molecular cloning and chromosomal mapping of a candidate cytokine gene selectively expressed in human CD34⁺ cells

A rare population of human bone marrow (BM) and cord blood (CB) mononuclear cells bearing the CD34 surface marker (CD34⁺) function as hematopoietic stem/progenitor cells. Cells lacking CD34 expression (CD34^-) in BM and CB are largely mature hematopoietic cells of various lineages that are derived from the CD34⁺ cells. To elucidate molecular mechanisms governing functional differences between CD34+ and CD34^- hematopoietic cells, we used representational difference analysis (RDA)-based subtraction to identify genes that are specifically or preferentially expressed in CD34⁺ cells. Among the 73 RDA fragments initially sequenced, 30% are derived from the CD34 and c-kit genes that are preferentially expressed in CD34⁺ cells. An additional 27 (37%) are novel or homologous only to entries in expressed sequence tag databases. One (C17) was found four times and is expressed in CD34⁺ but not in CD34^- cell populations from CB or BM. The cloned C17 cDNA encodes a novel polypeptide of 136 amino acids with a signal sequence. No homology to this peptide was found in the public databases. A secondary- structure analysis predicts that the C17 peptide contains four α-helices, a characteristic of hematopoietic cytokines and interleukins. This novel gene is mapped to human chromosome 4p15-p16. (C) 2000 Academic Press.