Human mast cells (MCs) were classified into at least two subtypes, i.e., tryptase-and chymasepositive MCs (MCTC) and tryptase-only-positive MCs (MCT). However, differences in global molecular expression between these subtypes are unknown. Methods: We analyzed public microarray data of MC subtypes derived from various tissues and those of peripheral blood granulocytes by using hierarchical clustering methods to understand the global gene expression profiles. Results: All the transcripts

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... to this clustering analysis were classified into two large clusters, i.e., MCpreferential or granulocyte-preferential. In the original works, MCs from tonsil, lung and skin had been cultured for more than several weeks to obtain highly viable and pure cell populations, and these MCs retained their typical profiles such as intensities of chymase protein expression. Most of the transcripts were commonly expressed by these MC subtypes. However, tonsil-derived MCs and skin-derived MCs but not lung-derived MCs expressed high levels of chymase (CMA1) as expected for the properties of MCTC and MCT. These CMA1-high MCs and CMA1-low MCs respectively expressed distinct sets of transcripts as small gene clusters as well as CMA-1 even after being cultured in the absence of a tissue environment. Conclusions: The MC lineage seems to be far from the granulocyte lineages including basophils. CMA1-high MCs (MCTC) and CMA1-low MCs (MCT) can be regarded as differentiated MC subtypes. As such, importance of data analysis studies will be increasing along with the accumulation of global molecular data in the public database.