Direct reprogramming of fibroblasts into renal tubular epithelial cells by defined transcription factors

Nat Cell Biol. 2016 Dec;18(12):1269-1280. doi: 10.1038/ncb3437. Epub 2016 Nov 7.


Direct reprogramming by forced expression of transcription factors can convert one cell type into another. Thus, desired cell types can be generated bypassing pluripotency. However, direct reprogramming towards renal cells remains an unmet challenge. Here, we identify renal cell fate-inducing factors on the basis of their tissue specificity and evolutionarily conserved expression, and demonstrate that combined expression of Emx2, Hnf1b, Hnf4a and Pax8 converts mouse and human fibroblasts into induced renal tubular epithelial cells (iRECs). iRECs exhibit epithelial features, a global gene expression profile resembling their native counterparts, functional properties of differentiated renal tubule cells and sensitivity to nephrotoxic substances. Furthermore, iRECs integrate into kidney organoids and form tubules in decellularized kidneys. Our approach demonstrates that reprogramming factors can be identified by targeted in silico analysis. Renal tubular epithelial cells generated ex vivo by forced expression of transcription factors may facilitate disease modelling, drug and nephrotoxicity testing, and regenerative approaches.

MeSH terms

  • Animals
  • Cell Aggregation
  • Cell Lineage
  • Cell Proliferation
  • Cell Shape
  • Cells, Cultured
  • Cellular Reprogramming*
  • Cluster Analysis
  • Embryo, Mammalian / cytology
  • Epithelial Cells / cytology*
  • Epithelial Cells / ultrastructure
  • Fibroblasts / cytology*
  • Fluorescent Antibody Technique
  • Gene Expression Profiling
  • Humans
  • Kidney Tubules / cytology*
  • Mice
  • Nephrons / cytology
  • Nephrons / metabolism
  • Organoids / cytology
  • Transcription Factors / metabolism*
  • Xenopus


  • Transcription Factors