A limited set of transcriptional programs define major cell types
We have produced RNA sequencing data for 53 primary cells from different locations in the human body. The clustering of these primary cells reveals that most cells in the human body share a few broad transcriptional programs, which define five major cell types: epithelial, endothelial, mesenchymal, neural, and blood cells. These act as basic components of many tissues and organs. Based on gene expression, these cell types redefine the basic histological types by which tissues have been traditionally classified. We identified genes whose expression is specific to these cell types, and from these genes, we estimated the contribution of the major cell types to the composition of human tissues. We found this cellular composition to be a characteristic signature of tissues and to reflect tissue morphological heterogeneity and histology. We identified changes in cellular composition in different tissues associated with age and sex, and found that departures from the normal cellular composition correlate with histological phenotypes associated with disease. ; This project was supported by awards U54HG007004, U41HG007234, and R01MH101814 from the National Human Genome Research Institute of the National Institutes of Health, as well as from the Spanish Ministry of Economy and Competitiveness, Centro de Excelencia Severo Ochoa 2013–2017, SEV-2012-0208, Programa de Ayudas FPI del Ministerio de Economía y Competitividad BES-2012-055848 to A.B., and Ministerio de Educación, Cultura y Deporte, under the FPU programme (Formación de Profesorado Universitario) with predoctoral fellowship FPU15/03635 to M.M.A., as well as the support of the CERCA programme/Generalitat de Catalunya. D.G.M. is supported by a "la Caixa"-Severo Ochoa predoctoral fellowship LCF/BQ/SO15/52260001. We also acknowledge support from the European Research Council (ERC) under the European Union's Seventh Framework Programme (FP7/2007-2013)/ERC grant agreement 294653.