Transgenic strategies to study podocyte loss and regeneration

Abstract

Podocyte death and regeneration are major topics in kidney research but remain controversial. Data obtained in humans demonstrate the existence of cells sited along Bowman's capsule that behave as podocyte progenitors in vitro and in in vivo mouse models of podocyte injury xenotrasplanted with this human-derived population. However, this podocyte reservoir still remains elusive in murine models, where it could be more easily studied. Transgenic models can be a powerful tool to identify this population and to better understand its dynamics and hierarchies in both physiological and pathological conditions. Indeed, exploiting transgenic approaches allows detecting, at the single cell level, movements, cell death, and replacement. Moreover, through lineage tracing it is now possible to identify specific population increase and to point out clonal expansions during or after the regenerative processes. However, applying transgenic strategies to study glomerular regeneration requires the search of markers to unequivocally identify this progenitor population. Achieving this aim would lead to a deep comprehension of the biological processes that underlie glomerular regeneration and clarify how different cell pools interface during this phase. Here we discuss strategies that have been used and new approaches in transgenic models finalized to study podocyte loss and subsequent replacement.