A limited set of transcriptional programs define major cell types
- Alessandra Breschi1,2,3,9,
- Manuel Muñoz-Aguirre1,4,9,
- Valentin Wucher1,9,
- Carrie A. Davis5,
- Diego Garrido-Martín1,2,
- Sarah Djebali1,2,6,
- Jesse Gillis3,
- Dmitri D. Pervouchine1,7,
- Anna Vlasova8,
- Alexander Dobin5,
- Chris Zaleski5,
- Jorg Drenkow5,
- Cassidy Danyko5,
- Alexandra Scavelli5,
- Ferran Reverter1,2,
- Michael P. Snyder3,
- Thomas R. Gingeras5 and
- Roderic Guigó1,2
- 1Centre for Genomic Regulation (CRG), The Barcelona Institute of Science and Technology, E-08003 Barcelona, Catalonia, Spain;
- 2Universitat Pompeu Fabra (UPF), E-08003 Barcelona, Catalonia, Spain;
- 3Department of Genetics, Stanford University, Stanford, California 94305, USA;
- 4Universitat Politècnica de Catalunya. Departament d'Estadística i Investigació Operativa, 08034 Barcelona, Catalonia, Spain;
- 5Cold Spring Harbor Laboratory, Cold Spring Harbor, New York 11742, USA;
- 6Institut National de Recherche en Santé Digestive (IRSD), Université de Toulouse, Institut National de la Santé et de la Recherche Médicale (INSERM), Institut National de Recherche pour l'Agriculture, l'Alimentation et l'Environnement (INRAE), École Nationale Vétérinaire de Toulouse (ENVT), Université Paul Sabatier (UPS), 31024 Toulouse, France;
- 7Skolkovo Institute for Science and Technology, Moscow, Russia 143025;
- 8Research Institute of Molecular Pathology (IMP), Vienna Biocenter (VBC), 1030 Vienna, Austria
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↵9 These authors contributed equally to this work.
Abstract
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.
Footnotes
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[Supplemental material is available for this article.]
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Article published online before print. Article, supplemental material, and publication date are at http://www.genome.org/cgi/doi/10.1101/gr.263186.120.
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Freely available online through the Genome Research Open Access option.
- Received March 10, 2020.
- Accepted April 29, 2020.
This article, published in Genome Research, is available under a Creative Commons License (Attribution-NonCommercial 4.0 International), as described at http://creativecommons.org/licenses/by-nc/4.0/.
