Functional analysis of co-expression networks of zebrafish ace2 reveals enrichment of pathways associated with development and disease

Keskus, Ayse Gokce; Tombaz, Melike; Arici, Burcin Irem; Dincaslan, Fatma Betul; Nabi, Afshan; Shehwana, Huma; Konu, Ozlen

Human Angiotensin I Converting Enzyme 2 (ACE2) plays essential roles in blood pressure regulation and SARS-CoV-2 entry. ACE2 has a highly conserved, one-to-one ortholog, called ace2, in zebrafish, which is an important model for human diseases. However, zebrafish ace2 expression profile has not yet been studied during early development, between genders, across different genotypes, or in disease. Moreover, a network-based meta-analysis for the extraction of functionally enriched pathways associated with differential ace2 expression is lacking in the literature. Herein, we first identified significant development-, tissue-, genotype- and gender-specific modulations in ace2 expression via meta-analysis of zebrafish Affymetrix transcriptomics datasets (ndatasets=107); and the correlation analysis of ace2 meta-differential expression profile revealed distinct positively and negatively correlated local functionally enriched gene networks. Moreover, we demonstrated that ace2 expression was significantly modulated under different physiological and pathological conditions related to development, tissue, gender, diet, infection, and inflammation using additional RNAseq datasets. Our findings implicate a novel translational role for zebrafish ace2 in organ differentiation and pathologies observed in the intestines and liver.