Exploring kidney allograft rejection: A proof-of-concept study using spatial transcriptomics.

Autor:	Martin-Martin C; Translational Immunology, Health Research Institute of the Principality of Asturias (ISPA), Avenida de Roma S/N, 33011, Oviedo, Asturias, Spain; RICORS2040, Kidney Disease Research Network, ISCIII, Madrid, Spain., Suarez-Alvarez B; Translational Immunology, Health Research Institute of the Principality of Asturias (ISPA), Avenida de Roma S/N, 33011, Oviedo, Asturias, Spain; RICORS2040, Kidney Disease Research Network, ISCIII, Madrid, Spain., González M; CIC bioGUNE, Basque Research and Technology Alliance (BRTA), Bizkaia Technology Park, 801 bld., 48160, Derio, Bizkaia, Spain., Torres IB; Department of Nephrology, Hospital Universitari Vall d'Hebron, Barcelona, Spain; Nephrology and Renal Transplant Laboratory, Vall Hebron Research Institute (VHIR), Barcelona, Spain; Department of Medicine, Autonomous University of Barcelona, Barcelona, Spain., Bestard O; Department of Nephrology, Hospital Universitari Vall d'Hebron, Barcelona, Spain; Nephrology and Renal Transplant Laboratory, Vall Hebron Research Institute (VHIR), Barcelona, Spain; Department of Medicine, Autonomous University of Barcelona, Barcelona, Spain., Martín JE; CIC bioGUNE, Basque Research and Technology Alliance (BRTA), Bizkaia Technology Park, 801 bld., 48160, Derio, Bizkaia, Spain., Barceló-Coblijn G; Lipids in Human Pathology, Institut d'Investigació Sanitària Illes Balears (IdISBa), Ctra. Valldemossa 79, E-07120 Palma, Balearic Islands, Spain; Research Unit, University Hospital Son Espases, Ctra. Valldemossa 79, E-07120 Palma, Balearic Islands, Spain., Moreso F; Department of Nephrology, Hospital Universitari Vall d'Hebron, Barcelona, Spain; Nephrology and Renal Transplant Laboratory, Vall Hebron Research Institute (VHIR), Barcelona, Spain; Department of Medicine, Autonomous University of Barcelona, Barcelona, Spain., Aransay AM; CIC bioGUNE, Basque Research and Technology Alliance (BRTA), Bizkaia Technology Park, 801 bld., 48160, Derio, Bizkaia, Spain; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Madrid, Spain., Lopez-Larrea C; Translational Immunology, Health Research Institute of the Principality of Asturias (ISPA), Avenida de Roma S/N, 33011, Oviedo, Asturias, Spain; RICORS2040, Kidney Disease Research Network, ISCIII, Madrid, Spain; Department of Immunology, Hospital Universitario Central de Asturias, 33011, Oviedo, Spain. Electronic address: inmuno@hca.es., Rodriguez RM; Lipids in Human Pathology, Institut d'Investigació Sanitària Illes Balears (IdISBa), Ctra. Valldemossa 79, E-07120 Palma, Balearic Islands, Spain; Research Unit, University Hospital Son Espases, Ctra. Valldemossa 79, E-07120 Palma, Balearic Islands, Spain.
Jazyk:	angličtina
Zdroj:	American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons [Am J Transplant] 2024 Jul; Vol. 24 (7), pp. 1161-1171. Date of Electronic Publication: 2024 Apr 29.
DOI:	10.1016/j.ajt.2024.04.015
Abstrakt:	In this proof-of-concept study, spatial transcriptomics combined with public single-cell ribonucleic acid-sequencing data were used to explore the potential of this technology to study kidney allograft rejection. We aimed to map gene expression patterns within diverse pathologic states by examining biopsies classified across nonrejection, T cell-mediated acute rejection, interstitial fibrosis, and tubular atrophy. Our results revealed distinct immune cell signatures, including those of T and B lymphocytes, monocytes, mast cells, and plasma cells, and their spatial organization within the renal interstitium. We also mapped chemokine receptors and ligands to study immune cell migration and recruitment. Finally, our analysis demonstrated differential spatial enrichment of transcription signatures associated with kidney allograft rejection across various biopsy regions. Interstitium regions displayed higher enrichment scores for rejection-associated gene expression patterns than tubular areas, which had negative scores. This implies that these signatures are primarily driven by processes unfolding in the renal interstitium. Overall, this study highlights the value of spatial transcriptomics for revealing cellular heterogeneity and immune signatures in renal transplant biopsies and demonstrates its potential for studying the molecular and cellular mechanisms associated with rejection. However, certain limitations must be borne in mind regarding the development and future applications of this technology. Competing Interests: Declaration of competing interest The authors of this manuscript have no conflicts of interest to disclose, as described by the American Journal of Transplantation. (Copyright © 2024 American Society of Transplantation & American Society of Transplant Surgeons. Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu