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Nat Rev Nephrol. 2015 Jul;11(7):420-31. doi: 10.1038/nrneph.2015.67. Epub 2015 May 12.

The use of lineage tracing to study kidney injury and regeneration.

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Excellence Centre for Research, Transfer and High Education for the development of DE NOVO Therapies (DENOTHE), University of Florence, Viale Pieraccini 6, 50139 Florence, Italy.
Stanford Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, CA 94305, USA.
Paediatric Stem Cell Research Institute &Division of Paediatric Nephrology, Edmond and Lily Safra Children's Hospital, Sheba Medical Centre, Tel Aviv University, Tel Aviv 52621, Israel.


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.

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