Suchergebnisse

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.

Post-mortem tissues samples are a key resource for investigating patterns of gene expression. However, the processes triggered by death and the post-mortem interval (PMI) can significantly alter physiologically normal RNA levels. We investigate the impact of PMI on gene expression using data from multiple tissues of post-mortem donors obtained from the GTEx project. We find that many genes change expression over relatively short PMIs in a tissue-specific manner, but this potentially confounding effect in a biological analysis can be minimized by taking into account appropriate covariates. By comparing ante- and post-mortem blood samples, we identify the cascade of transcriptional events triggered by death of the organism. These events do not appear to simply reflect stochastic variation resulting from mRNA degradation, but active and ongoing regulation of transcription. Finally, we develop a model to predict the time since death from the analysis of the transcriptome of a few readily accessible tissues. ; This work was supported by the following grants and contracts: 1) From the US NIH: Contract HHSN261200800001E (Leidos Prime contract with NCI); Contracts 10XS170 (NDRI), 10XS171 (Roswell Park Cancer Institute), 10 × 172 (Science Care Inc.), and 12ST1039 (IDOX); Contract 10ST1035 (Van Andel Institute); Contract HHSN268201000029C (Broad Institute); R01 DA006227-17 (U Miami Brain Bank) 2) Ipatimup and i3s are partially funded by the Portuguese Foundation for Science and Technology (FCT); FEDER funds through the COMPETE 2020—Operacional Programme for Competitiveness and Internationalization (POCI), Portugal 2020, and by Portuguese funds through FCT/MCTES in the framework POCI-01-0145-FEDER-007274; 3) NORTE-01-0145-FEDER-000029, supported by NORTE 2020, under the PORTUGAL 2020 Partnership Agreement, through the European Regional Development Fund (ERDF); 4) FCT Fellowships SFRH/BPD/89764/2012 to PO, PD/BD/128007/2016 to AS; Salary support to PGF by POPH—QREN Type 4.2, European Social Fund and MCTES, program Investigador FCT, IF/01127/2014. 5) BIO2014-57291-R from the Spanish Ministry of Economy and Competitiveness and "Plataforma de Recursos Biomoleculares y Bioinformáticos" PT13/0001/0007 from the ISCIII, and EU H2020-INFRADEV-1-2015-1 ELIXIR-EXCELERATE (ref. 6,676559) Spanish Ministry of Economy and Competitiveness, 'Centro de Excelencia Severo Ochoa 2013-2017' and CERCA Programme/Generalitat de Catalunya, 7) Ministerio de Educación, Cultura y Deporte, under the FPU programme (Formación de Profesorado Universitario) with pre-doctoral fellowship FPU15/03635 to MMA. 8) Award Number 1R01MH101814 and 3R01MH101814-03S1 from the National Human Genome Research Institute. European Research Council under the European Union's Seventh Framework Programme (FP7/2007-2013) / ERC grant agreement RNA-MAPS_294653, Ministerio de Economía, Industria y Competitividad, referencia MEIC BIO2015-70777-P y los Fondos Estructurales de la Unión Europea (FEDER) and ISCIII del Ministerio de Economía y Competitividad, referencia PT13/0001/0021 cofinaciada por el Fondo Europeo de Desarrollo Regional (FEDER). 9) MS received funding from CNPq (grant 310132/2015-0 and 427541/2016-6), and from FAPERJ (grant E_06/2015).