Conundrums of choice of 'normal' kidney tissue for single cell studies

Purpose of reviewDefining molecular changes in key kidney cell types across lifespan and in disease states is essential to understand the pathogenetic basis of disease progression and targeted therapies. Various single cell approaches are being applied to define disease associated molecular signatures. Key considerations include the choice of reference tissue or 'normal' for comparison to diseased human specimens and a benchmark reference atlas. We provide an overview of select single cell technologies, key considerations for experimental design, quality control, choices and challenges associated with assay type and source for reference tissue.Recent findingsSeveral initiatives including Kidney Precision Medicine Project, Human Biomolecular Molecular Atlas Project, Genitourinary Disease Molecular Anatomy Project, ReBuilding a Kidney consortium, Human Cell Atlas and Chan Zuckerburg Initiative are generating single cell atlases of 'normal' or disease kidney. Different sources of kidney tissue are used as reference. Signatures of injury, resident pathology and procurement associated biological and technical artifacts have been identified in human kidney reference tissue.SummaryCommitting to a particular reference or 'normal' tissue has significant implications in interpretation of data from disease samples or in ageing. Voluntarily donated kidney tissue from healthy individuals is generally unfeasible. Having reference datasets for different types of 'normal' tissue can aid in mitigating the confounds of choice of reference tissue and sampling biases.