title: Transcriptomic analysis reveals metabolic switches and surface remodeling as key processes for stage transition inTrypanosoma cruzi.
abstract: American trypanosomiasis is a chronic and endemic disease which affects millions of people.Trypanosoma cruzi, its causative agent, has a life cycle that involves complex morphological and functional transitions, as well as a variety of environmental conditions. This requires a tight regulation of gene expression, which is achieved mainly by post-transcriptional regulation. In this work we conducted an RNAseq analysis of the three major life cycle stages ofT. cruzi: amastigotes, epimastigotes and trypomastigotes. This analysis allowed us to delineate specific transcriptomic profiling for each stage, and also to identify those biological processes of major relevance in each state. Stage specific expression profiling evidenced the plasticity ofT. cruzito adapt quickly to different conditions, with particular focus on membrane remodeling and metabolic shifts along the life cycle. Epimastigotes, which replicate in the gut of insect vectors, showed higher expression of genes related to energy metabolism, mainly Krebs cycle, respiratory chain and oxidative phosphorylation related genes, and anabolism related genes associated to nucleotide and steroid biosynthesis; also, a general down-regulation of surface glycoprotein coding genes was seen at this stage. Trypomastigotes, living extracellularly in the bloodstream of mammals, express a plethora of surface proteins and signaling genes involved in invasion and evasion of immune response. Amastigotes mostly express membrane transporters and genes involved in regulation of cell cycle, and also express a specific subset of surface glycoprotein coding genes. In addition, these results allowed us to improve the annotation of the Dm28c genome, identifying new ORFs and set the stage for construction of networks of co-expression, which can give clues about coded proteins of unknown functions.
authors.affiliation: Unidad de Biología Molecular, Institut Pasteur de Montevideo, Montevideo, Uruguay.
authors.forename: Luisa
authors.initials: L
authors.lastname: Berná
authors.affiliation: Unidad de Biología Molecular, Institut Pasteur de Montevideo, Montevideo, Uruguay.|Departamento de Bioquímica, Facultad de Medicina, Universidad de la República, Montevideo, Uruguay.
authors.forename: Maria Laura
authors.initials: ML
authors.lastname: Chiribao
authors.affiliation: Unidad de Biología Molecular, Institut Pasteur de Montevideo, Montevideo, Uruguay.
authors.forename: Gonzalo
authors.initials: G
authors.lastname: Greif
authors.affiliation: Sección Biomatemática, Unidad de Genómica Evolutiva, Facultad de Ciencias, Universidad de la República, Montevideo, Uruguay.
authors.forename: Matias
authors.initials: M
authors.lastname: Rodriguez
authors.affiliation: Sección Biomatemática, Unidad de Genómica Evolutiva, Facultad de Ciencias, Universidad de la República, Montevideo, Uruguay.
authors.forename: Fernando
authors.initials: F
authors.lastname: Alvarez-Valin
authors.affiliation: Unidad de Biología Molecular, Institut Pasteur de Montevideo, Montevideo, Uruguay.|Departamento de Bioquímica, Facultad de Medicina, Universidad de la República, Montevideo, Uruguay.
authors.forename: Carlos
authors.initials: C
authors.lastname: Robello
keywords: Chagas disease; Metabolic regulation; RNA-seq; Surface proteins; Trypanosoma cruzi