Comprehensive Analysis of Ubiquitously Expressed Genes in Humans from A Data-driven Perspective

Comprehensive characterization of spatial and temporal gene expression patterns in humans is critical for uncovering the regulatory codes of the human genome and understanding the molecular mechanisms of human diseases.Ubiquitously expressed genes(UEGs)refer to the genes expressed across a majority of,if not all,phenotypic and physiological conditions of an organism.It is known that many human genes are broadly expressed across tissues.However,most previous UEG studies have only focused on providing a list of UEGs without capturing their global expression patterns,thus limiting the potential use of UEG information.In this study,we proposed a novel data-driven framework to leverage the extensive collection of40,000 human transcriptomes to derive a list of UEGs and their corresponding global expression patterns,which offers a valuable resource to further characterize human transcriptome.Our results suggest that about half(12,234;49.01%)of the human genes are expressed in at least 80%of human transcriptomes,and the median size of the human transcriptome is 16,342 genes(65.44%).Through gene clustering,we identified a set of UEGs,named LoVarUEGs,which have stable expression across human transcriptomes and can be used as internal reference genes for expression measurement.To further demonstrate the usefulness of this resource,we evaluated the global expression patterns for 16 previously predicted disallowed genes in islet beta cells and found that seven of these genes showed relatively more varied expression patterns,suggesting that the repression of these genes may not be unique to islet beta cells.

Toll-like receptor 7 deficiency suppresses type 1 diabetes development by modulating B-cell differentiation and function

Innate immunity mediated by Toll-like receptors(TLRs),which can recognize pathogen molecular patterns,plays a critical role in type 1 diabetes development.TLR7 is a pattern recognition receptor that senses single-stranded RNAs from viruses and host tissue cells;however,its role in type 1 diabetes development remains unclear.In our study,we discovered that Tlr7-deficient(Tlr7^(−/−))nonobese diabetic(NOD)mice,a model of human type 1 diabetes,exhibited a significantly delayed onset and reduced incidence of type 1 diabetes compared with Tlr7-sufficient(Tlr7^(+/+))NOD mice.Mechanistic investigations showed that Tlr7 deficiency significantly altered B-cell differentiation and immunoglobulin production.Moreover,Tlr7^(−/−)NOD B cells were found to suppress diabetogenic CD4^(+)T-cell responses and protect immunodeficient NOD mice from developing diabetes induced by diabetogenic T cells.In addition,we found that Tlr7 deficiency suppressed the antigen-presenting functions of B cells and inhibited cytotoxic CD8^(+)T-cell activation by downregulating the expression of both nonclassical and classical MHC class I(MHC-I)molecules on B cells.Our data suggest that TLR7 contributes to type 1 diabetes development by regulating B-cell functions and subsequent interactions with T cells.Therefore,therapeutically targeting TLR7 may prove beneficial for disease protection.