Dissecting Normal and Abnormal Human Kidney Development Using Multiomics
Journal of the American Society of Nephrology, vol. 37, pp. 585–595
Abstract
Congenital kidney anomalies frequently lead to development of CKD in children and adults, with limited possibility for accurate prognostication and successful intervention. Causal genetic variants are identified in a minority of individuals, while the biologic interpretation of putative genetic variants and their effect on kidney development and CKD remains incompletely understood. Advances in single-cell and spatial multiomics now enable a deeper biologic understanding and interpretation of disease-causing mechanisms of congenital kidney anomalies, holding promise for precise diagnoses, prognostication, and treatment for patients. In this review, we provide an overview of multiomics approaches, including transcriptomics, epigenomics, proteomics, and metabolomics, for characterizing and understanding the biology of human kidney development and disease. We will discuss the technical capabilities and challenges in mapping the spatial distribution of normal and abnormal developmental processes in the kidney. Moreover, we present three key multiomics case studies and discuss their experimental design considerations. Finally, future directions and the potential effect of multiomics approaches on the biologic understanding of kidney disease in development and adulthood are discussed. This review highlights that by integrating molecular insights, multiomics has the potential to transform our understanding of genetic (or variant-driven) and nongenetic kidney disease mechanisms and to advance precision diagnostics, prognostics, and therapies for congenital kidney anomalies.
Authors 7
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Amsterdam UMC Location University of Amsterdam · Emma Kinderziekenhuis
Affiliation as printed
Department of Pediatric Nephrology, Emma Children's Hospital – Amsterdam UMC location University of Amsterdam, Amsterdam, The Netherlands
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Affiliation as printed
Division of Nephrology and Clinical Immunology, Medical Faculty, RWTH Aachen University, Aachen, Germany
RWTH Aachen University, Medical Faculty, Division of Nephrology and Clinical Immunology, Aachen, Germany
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Amsterdam UMC Location University of Amsterdam · Emma Kinderziekenhuis
Affiliation as printed
Department of Pediatric Nephrology, Emma Children's Hospital – Amsterdam UMC location University of Amsterdam, Amsterdam, The Netherlands
Emma Center for Personalized Medicine, Amsterdam UMC Location University of Amsterdam, Amsterdam, The Netherlands
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Amsterdam UMC Location University of Amsterdam · Emma Kinderziekenhuis
Affiliation as printed
Department of Pediatric Nephrology, Emma Children's Hospital – Amsterdam UMC location University of Amsterdam, Amsterdam, The Netherlands
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Amsterdam UMC Location University of Amsterdam · Emma Kinderziekenhuis
Affiliation as printed
Department of Pediatric Nephrology, Emma Children's Hospital – Amsterdam UMC location University of Amsterdam, Amsterdam, The Netherlands
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Affiliation as printed
Division of Nephrology and Clinical Immunology, Medical Faculty, RWTH Aachen University, Aachen, Germany
RWTH Aachen University, Medical Faculty, Division of Nephrology and Clinical Immunology, Aachen, Germany
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Amsterdam UMC Location University of Amsterdam · Emma Kinderziekenhuis
Affiliation as printed
Department of Pediatric Nephrology, Emma Children's Hospital – Amsterdam UMC location University of Amsterdam, Amsterdam, The Netherlands
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