Detection of renin lineage cell transdifferentiation to podocytes in the kidney glomerulus with dual lineage tracing

Diana G. Eng, Natalya V. Kaverina, Remington R.S. Schneider, Benjamin S. Freedman, Kenneth W. Gross, Jeffrey H. Miner, Jeffrey W. Pippin, Stuart J. Shankland

Research output: Contribution to journalArticle

13 Scopus citations

Abstract

Understanding of cellular transdifferentiation is limited by the technical inability to track multiple lineages in vivo. To overcome this we developed a new tool to simultaneously fate map two distinct cell types in the kidney, and genetically test whether cells of renin lineage (CoRL) can transdifferentiate to a podocyte fate. Ren1cCreER/tdTomato/Nphs1-FLPo/FRT-EGFP mice (CoRL-PODO mice) were generated by crossing Ren1c-CreER/tdTomato CoRL reporter mice with Nphs1-FLPo/FRT-EGFP podocyte reporter mice. Following tamoxifen administration in these animals, CoRL were labeled with red fluorescence (tdTomato) and co-localized with renin. Podocytes were labeled green (enhanced green fluorescent protein) and co-localized with nephrin. Following podocyte loss by nephrotoxic antibody and subsequent enalapril-enhanced partial replacement, tdTomato-EGFP-labeled CoRL were detected as yellow-colored cells in a subset of glomerular tufts, without the use of antibodies. Co-localization with podocin indicated that these cells are podocytes, derived from CoRL origin. Thus, our novel study shows that two distinct cell types can be simultaneously labeled in the mouse kidney and provide strong genetic evidence in vivo that lost podocytes can be replaced in part by CoRL.

Original languageEnglish
Pages (from-to)1240-1246
Number of pages7
JournalKidney International
Volume93
Issue number5
DOIs
StatePublished - May 2018

Keywords

  • Cre-recombination
  • FLP-recombination reporter mouse
  • enalapril
  • glomerulus
  • lineage tracing
  • migration
  • podocin

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    Eng, D. G., Kaverina, N. V., Schneider, R. R. S., Freedman, B. S., Gross, K. W., Miner, J. H., Pippin, J. W., & Shankland, S. J. (2018). Detection of renin lineage cell transdifferentiation to podocytes in the kidney glomerulus with dual lineage tracing. Kidney International, 93(5), 1240-1246. https://doi.org/10.1016/j.kint.2018.01.014