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

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 factor...

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Bibliographic Details
Published in:Nature cell biology Vol. 18; no. 12; pp. 1269 - 1280
Main Authors: Kaminski, Michael M., Tosic, Jelena, Kresbach, Catena, Engel, Hannes, Klockenbusch, Jonas, Müller, Anna-Lena, Pichler, Roman, Grahammer, Florian, Kretz, Oliver, Huber, Tobias B., Walz, Gerd, Arnold, Sebastian J., Lienkamp, Soeren S.
Format: Journal Article
Language:English
Published: London Nature Publishing Group UK 01.12.2016
Nature Publishing Group
Subjects:
631/136/142
631/136/334/1874/345
631/136/334/1874/761
631/532/2435
Analysis
Animals
Biology
Cancer Research
Cell Aggregation
Cell Biology
Cell Lineage
Cell Proliferation
Cell Shape
Cells, Cultured
Cellular Reprogramming
Cluster Analysis
Developmental Biology
Embryo, Mammalian - cytology
Epithelial Cells - cytology
Epithelial Cells - ultrastructure
Fibroblasts
Fibroblasts - cytology
Fluorescent Antibody Technique
Gene expression
Gene Expression Profiling
Genetic aspects
Humans
Kidney Tubules - cytology
Kidneys
Life Sciences
Medicine
Mice
Nephrons - cytology
Nephrons - metabolism
Organoids - cytology
Physiological aspects
Renal tubule
Stem Cells
Transcription factors
Transcription Factors - metabolism
Xenopus
Germany
ISSN:1465-7392, 1476-4679, 1476-4679
Online Access:Get full text
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Summary: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. Kaminski  et al.  demonstrate that combined expression of the transcription factors Emx2, Hnf1b, Hnf4a and Pax8 converts mouse and human fibroblasts into induced renal tubular epithelial cells.
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ISSN:1465-7392
1476-4679
1476-4679
DOI:10.1038/ncb3437