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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Vydáno v:	Nature cell biology Ročník 18; číslo 12; s. 1269 - 1280
Hlavní autoři:	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.
Médium:	Journal Article
Jazyk:	angličtina
Vydáno:	London Nature Publishing Group UK 01.12.2016 Nature Publishing Group
Témata:	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
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Shrnutí:	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.
Bibliografie:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 14 content type line 23
ISSN:	1465-7392 1476-4679 1476-4679
DOI:	10.1038/ncb3437