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

Standard

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, Vol. 18, No. 12, 12.2016, p. 1269-1280.

Research output: SCORING: Contribution to journalSCORING: Journal articleResearchpeer-review

Harvard

Kaminski, MM, Tosic, J, Kresbach, C, Engel, H, Klockenbusch, J, Müller, A-L, Pichler, R, Grahammer, F, Kretz, O, Huber, TB, Walz, G, Arnold, SJ & Lienkamp, SS 2016, 'Direct reprogramming of fibroblasts into renal tubular epithelial cells by defined transcription factors', NAT CELL BIOL, vol. 18, no. 12, pp. 1269-1280. https://doi.org/10.1038/ncb3437

APA

Kaminski, M. M., Tosic, J., Kresbach, C., Engel, H., Klockenbusch, J., Müller, A-L., Pichler, R., Grahammer, F., Kretz, O., Huber, T. B., Walz, G., Arnold, S. J., & Lienkamp, S. S. (2016). Direct reprogramming of fibroblasts into renal tubular epithelial cells by defined transcription factors. NAT CELL BIOL, 18(12), 1269-1280. https://doi.org/10.1038/ncb3437

Vancouver

Kaminski MM, Tosic J, Kresbach C, Engel H, Klockenbusch J, Müller A-L et al. Direct reprogramming of fibroblasts into renal tubular epithelial cells by defined transcription factors. NAT CELL BIOL. 2016 Dec;18(12):1269-1280. https://doi.org/10.1038/ncb3437

Bibtex

@article{ca971050dbea4c339cc0d03f330e5617,
title = "Direct reprogramming of fibroblasts into renal tubular epithelial cells by defined transcription factors",
abstract = "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.",
keywords = "Animals, Cell Aggregation, Cell Lineage, Cell Proliferation, Cell Shape, Cells, Cultured, Cellular Reprogramming, Cluster Analysis, Embryo, Mammalian, Epithelial Cells, Fibroblasts, Fluorescent Antibody Technique, Gene Expression Profiling, Humans, Kidney Tubules, Mice, Nephrons, Organoids, Transcription Factors, Xenopus, Journal Article",
author = "Kaminski, {Michael M} and Jelena Tosic and Catena Kresbach and Hannes Engel and Jonas Klockenbusch and Anna-Lena M{\"u}ller and Roman Pichler and Florian Grahammer and Oliver Kretz and Huber, {Tobias B} and Gerd Walz and Arnold, {Sebastian J} and Lienkamp, {Soeren S}",
year = "2016",
month = dec,
doi = "10.1038/ncb3437",
language = "English",
volume = "18",
pages = "1269--1280",
journal = "NAT CELL BIOL",
issn = "1465-7392",
publisher = "NATURE PUBLISHING GROUP",
number = "12",

}

RIS

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 -