Analysis of the structure, evolution, and expression of CD24, an important regulator of cell fate

CD24 is a small, glycophosphatidylinositol-anchored cell surface receptor, expressed in a variety of cells types and tissues. CD24 gene and protein expression is highly dynamic in response to cellular differentiation and stimulation in a cell-specific manner. Furthermore, CD24 interacts with a diverse collection of ligands, including cell adhesion molecules such as P-selectin, and the immune-associated siglec family of transmembrane proteins. While much is known regarding the biological roles of CD24 in regulating cell survival, death and differentiation, little is known about the evolution and organization of CD24 across species or the relationship between CD24 expression and its known ligands. We analyzed the organization and evolution of the CD24 gene from 56 mammalian, avian and reptilian species. We further examined the mRNA expression of CD24 and its known ligands in Mus musculus in immune cells, immunologically privileged tissues, developing brain, and developing and regenerating liver. CD24 arose prior to the reptilian–avian divergence and is conserved across many mammalian species, although we were unable to identify CD24 in marsupials or monotremes. The CD24 genomic structure is diverse between and within species, with varying numbers of exons, introns, and the presence of untranslated regions. Of note, we found no obvious criteria distinguishing CD24 genes from those annotated as CD24-like. The expression of CD24 is similarly complex, with immune cells showing dynamic changes in mRNA levels during development, while immunologically privileged and developing tissues show a high, static expression level that decreases in mature tissues. Furthermore, the expression of CD24 correlated with some but not all of its known ligands in a tissues-specific manner, suggesting that novel ligands have yet to be identified and that cell-specific ligand expression can influence CD24 function. We find that CD24 arose prior to the divergence of reptiles, birds and mammals. Furthermore, the most highly conserved areas of the protein are the amino acids which can be glycosylated. We also find that CD24 expression is highly tissue-specific and in many cases, not well conserved with known CD24 ligands, suggesting yet-unknown CD24–ligand interactions. Together, these data are a valuable resource for furthering studies in CD24 biology.