Direct reprogramming of fibroblasts into renal tubular epithelial cells by defined transcription factors
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Direct reprogramming of fibroblasts into renal tubular epithelial cells by defined transcription factors. / 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.
in: NAT CELL BIOL, Jahrgang 18, Nr. 12, 12.2016, S. 1269-1280.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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TY - JOUR
T1 - Direct reprogramming of fibroblasts into renal tubular epithelial cells by defined transcription factors
AU - Kaminski, Michael M
AU - Tosic, Jelena
AU - Kresbach, Catena
AU - Engel, Hannes
AU - Klockenbusch, Jonas
AU - Müller, Anna-Lena
AU - Pichler, Roman
AU - Grahammer, Florian
AU - Kretz, Oliver
AU - Huber, Tobias B
AU - Walz, Gerd
AU - Arnold, Sebastian J
AU - Lienkamp, Soeren S
PY - 2016/12
Y1 - 2016/12
N2 - 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.
AB - 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.
KW - Animals
KW - Cell Aggregation
KW - Cell Lineage
KW - Cell Proliferation
KW - Cell Shape
KW - Cells, Cultured
KW - Cellular Reprogramming
KW - Cluster Analysis
KW - Embryo, Mammalian
KW - Epithelial Cells
KW - Fibroblasts
KW - Fluorescent Antibody Technique
KW - Gene Expression Profiling
KW - Humans
KW - Kidney Tubules
KW - Mice
KW - Nephrons
KW - Organoids
KW - Transcription Factors
KW - Xenopus
KW - Journal Article
U2 - 10.1038/ncb3437
DO - 10.1038/ncb3437
M3 - SCORING: Journal article
C2 - 27820600
VL - 18
SP - 1269
EP - 1280
JO - NAT CELL BIOL
JF - NAT CELL BIOL
SN - 1465-7392
IS - 12
ER -