Stage-specific transcriptomic signatures in Trypanosoma cruzi are largely conserved across genetic diversity

Abstract Background The kinetoplastid parasite Trypanosoma cruzi is the causative agent of Chagas disease. Seven discrete typing units (DTUs) are recognized within this genetically heterogeneous species. During its life cycle, T. cruzi adopts different developmental forms adapted to sustain infection in triatomines or mammalian hosts, namely epimastigote, metacyclic trypomastigote (MT), amastigote, and blood form trypomastigote (represented in vitro by their experimental proxy, tissue culture-derived trypomastigotes [TCTs]). Methods Here, we analyzed data from 86 publicly available RNA-seq libraries to explore the global transcriptional profiles at each of these 4 major developmental stages, including data from multiple strains and DTUs (TcI, TcII, TcVI). Results Our results reveal conserved transcriptional programs associated with each stage, even across diverse parasite lineages. For example, epimastigotes display increased protein synthesis and energy metabolism; this is also observed during the transitory phases of TCTs to intracellular amastigotes. From TCTs to epimastigotes, a shared subset of 244 differentially expressed orthologous groups was identified, suggesting common replicative mechanisms in these 2 parasite forms. Additionally, the transition to amastigote form involves the overexpression of orthologous groups associated with metabolism, protein synthesis, and DNA repair, while the transition to TCT involves the activation of functions such as motility and signaling, and overexpression of surface proteins such as mucins and trans-sialidases. However, in MT, the form responsible for transmitting infection from vector to mammalian host, transcriptional signatures are strongly influenced by the strain, possibly indicating host adaptation. Additionally, different in vitro metacyclogenesis-induction methods elicit divergent transcriptional programs in the parasite, and the model that best reflects in vivo MT properties remains to be determined. Conclusions Our results provide key insights into the gene expression dynamics of T. cruzi , highlighting molecular adaptations linked to life cycle stage, strain, and experimental conditions. Additionally, this work allows us to define the core standard landscape of T. cruzi ’s transcriptome, providing a benchmark consensus resource for future transcriptomic studies.