The use of lineage tracing to study kidney injury and regeneration

Lineage tracing is a sophisticated technique to track cellsin vivo. Here, Paola Romagnani and colleagues describe how lineage tracing can be used to track the fate of cells involved in renal development, pathophysiological changes and regeneration. The authors discuss considerations in selecting an appropriate reporter, promoter, and activating switch for lineage tracing experiments, and approaches to data interpretation. Lineage tracing is a powerful tool to track cells in vivo and provides enhanced spatial, temporal, and kinetic resolution of the mechanisms that underlie tissue renewal and repair. The data obtained from novel mouse models engineered for lineage tracing has started to transform our understanding of the changes in cell fate that underlie renal pathophysiology, the role of stem and/or progenitor cells in kidney development, and the mechanisms of kidney regeneration. The complexity of the genetic systems that are engineered for lineage tracing requires careful analysis and interpretation. In this Review we emphasize that close attention in lineage tracing studies must be paid to the specificity of the promoter, the use of drug-controlled activation of Cre recombinase as a genetic switch, and the type of reporter that should be engineered into lineage tracing genetic constructs. We evaluate the optimal experimental conditions required to achieve the pre-specified aims of the study and discuss the novel genetic techniques that are becoming available to study putative renal progenitor cells and the mechanisms of kidney regeneration.