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

Publication: Genome
4 October 2021

Abstract

Human Angiotensin I Converting Enzyme 2 (ACE2) plays an essential role in blood pressure regulation and SARS-CoV-2 entry. ACE2 has a highly conserved, one-to-one ortholog (ace2) in zebrafish, which is an important model for human diseases. However, the 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 RNA-seq datasets. Our findings implicate a novel translational role for zebrafish ace2 in organ differentiation and pathologies observed in the intestines and liver.

Résumé

L’enzyme humaine de conversion de l’angiotensine 2 (ACE2) joue des rôles essentiels dans la régulation de la tension artérielle et l’entrée du SARS-CoV-2. L’ACE2 possède un orthologue direct très conservé (ace2) chez le poisson-zèbre, un organisme modèle important dans l’étude des maladies humaines. Cependant, le profil d’expression du gène ace2 chez le poisson-zèbre n’a pas encore été étudié au cours des premiers stades de développement, chez les deux sexes, au sein de différents génotypes et en cas de maladie. De plus, aucune méta-analyse fondée sur les réseaux n’a encore été faite pour identifier les sentiers fonctionnels qui sont enrichis en fonction de l’expression différentielle du gène ace2. Dans ce travail, les auteurs ont d’abord identifié des modulations spécifiques dans l’expression d’ace2 en fonction du stade de développement, du tissu, du génotype ou du sexe via une méta-analyse des jeux de données transcriptomiques Affymetrix pour le poisson-zèbre (njeux = 107). Une analyse de corrélation des profils d’expression méta-différentiels d’ace2 mis a au jour des réseaux géniques locaux distincts, à corrélation à la fois positive et négative, qui reflétaient un enrichissement fonctionnel. De plus, les auteurs ont démontré que l’expression d’ace2 était modulée de manière significative en fonction des conditions physiologiques et pathologiques liées au stade de développement, au tissu, au sexe, à la diète, à l’infection et à l’inflammation en utilisant des jeux de données RNA-seq additionnels. Ces résultats impliquent un rôle traductionnel inédit pour le gène ace2 du poisson-zèbre dans la différentiation des organes et des pathologies observées dans l’intestin et le foie. [Traduit par la Rédaction]

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Published In

cover image Genome
Genome
Volume 65Number 2February 2022
Pages: 57 - 74

History

Received: 26 March 2021
Accepted: 22 September 2021
Accepted manuscript online: 4 October 2021
Version of record online: 4 October 2021

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Key Words

  1. zebrafish
  2. ace2
  3. transcriptome
  4. network analysis
  5. meta-analysis

Mots-clés

  1. poisson-zèbre
  2. ace2
  3. transcriptome
  4. analyse de réseaux
  5. méta-analyse

Authors

Affiliations

Ayse Gokce Keskus
Interdisciplinary Program in Neuroscience, Bilkent University, Ankara, Turkey.
Melike Tombaz
Department of Molecular Biology and Genetics, Bilkent University, Ankara, Turkey.
Burcin Irem Arici
Department of Molecular Biology and Genetics, Bilkent University, Ankara, Turkey.
Fatma Betul Dincaslan
Department of Molecular Biology and Genetics, Bilkent University, Ankara, Turkey.
Afshan Nabi
Department of Molecular Biology and Genetics, Bilkent University, Ankara, Turkey.
Faculty of Engineering and Natural Sciences, Sabancı University, Istanbul, Turkey.
Huma Shehwana
Department of Molecular Biology and Genetics, Bilkent University, Ankara, Turkey.
Department of Biological Sciences, National University of Medical Sciences, Rawalpindi, Pakistan.
Interdisciplinary Program in Neuroscience, Bilkent University, Ankara, Turkey.
Department of Molecular Biology and Genetics, Bilkent University, Ankara, Turkey.
UNAM-Institute of Materials Science and Nanotechnology, Bilkent University, Ankara, Turkey.

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