Identification of pro-fibrotic macrophage populations by single-cell transcriptomic analysis in West Highland white terriers affected with canine idiopathic pulmonary fibrosis.
[en] Canine idiopathic pulmonary fibrosis (CIPF) affects old dogs from the West Highland white terrier (WHWT) breed and mimics idiopathic pulmonary fibrosis (IPF) in human. The disease results from deposition of fibrotic tissue in the lung parenchyma causing respiratory failure. Recent studies in IPF using single-cell RNA sequencing (scRNA-seq) revealed the presence of profibrotic macrophage populations in the lung, which could be targeted for therapeutic purpose. In dogs, scRNA-seq was recently validated for the detection of cell populations in bronchoalveolar lavage fluid (BALF) from healthy dogs. Here we used the scRNA-seq to characterize disease-related heterogeneity within cell populations of macrophages/monocytes (Ma/Mo) in the BALF from 5 WHWTs affected with CIPF in comparison with 3 healthy WHWTs. Gene set enrichment analysis was also used to assess pro-fibrotic capacities of Ma/Mo populations. Five clusters of Ma/Mo were identified. Gene set enrichment analyses revealed the presence of pro-fibrotic monocytes in higher proportion in CIPF WHWTs than in healthy WHWTs. In addition, monocytes-derived macrophages enriched in pro-fibrotic genes in CIPF compared with healthy WHWTs were also identified. These results suggest the implication of Ma/Mo clusters in CIPF processes, although, further research is needed to understand their role in disease pathogenesis. Overexpressed molecules associated with pulmonary fibrosis processes were also identified that could be used as biomarkers and/or therapeutic targets in the future.
Disciplines :
Veterinary medicine & animal health Biochemistry, biophysics & molecular biology
Author, co-author :
Fastrès, Aline ; Université de Liège - ULiège > Dép. clinique des animaux de compagnie et des équidés (DCA) > Médecine interne des animaux de compagnie
Pirottin, Dimitri ; Université de Liège - ULiège > Département des sciences fonctionnelles (DSF) > Département des sciences fonctionnelles (DSF)
Fievez, Laurence ; Université de Liège - ULiège > I3-Cellular and Molecular Immunology
Tutunaru, Alexandru-Cosmin ; Université de Liège - ULiège > Dép. clinique des animaux de compagnie et des équidés (DCA) > Anesthésiologie gén. et pathologie chirurg. des grds animaux
Bolen, Géraldine ; Université de Liège - ULiège > Dép. clinique des animaux de compagnie et des équidés (DCA) > Imagerie médicale
Merveille, Anne-Christine ; Université de Liège - ULiège > Dép. clinique des animaux de compagnie et des équidés (DCA) > Pathologie médicale des petits animaux
Marichal, Thomas ; Université de Liège - ULiège > I3-Immunophysiology
Desmet, Christophe ; Université de Liège - ULiège > I3-Cellular and Molecular Immunology
Bureau, Fabrice ; Université de Liège - ULiège > Vice-Recteur à la Recherche
Clercx, Cécile ; Université de Liège - ULiège > Dép. clinique des animaux de compagnie et des équidés (DCA) > Pathologie médicale des petits animaux
Language :
English
Title :
Identification of pro-fibrotic macrophage populations by single-cell transcriptomic analysis in West Highland white terriers affected with canine idiopathic pulmonary fibrosis.
Publication date :
15 December 2020
Journal title :
Frontiers in Immunology
eISSN :
1664-3224
Publisher :
Frontiers Media S.A., Switzerland
Special issue title :
Comparative Immunology
Volume :
11
Pages :
611749
Peer reviewed :
Peer Reviewed verified by ORBi
Funders :
ULg FSR - Université de Liège. Fonds spéciaux pour la recherche [BE]
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