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Transient p53 suppression increases reprogramming of human fibroblasts without affecting apoptosis and DNA damage

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Rasmussen, M. A., Holst, B., Tümer, Z., Johnsen, M. G., Zhou, S., Stummann, T. C., Hyttel, P., & Clausen, C. (2014). Transient p53 suppression increases reprogramming of human fibroblasts without affecting apoptosis and DNA damage. Stem Cell Reviews, 3(3), 404-13. https://doi.org/10.1016/j.stemcr.2014.07.006

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Author

Rasmussen, Mikkel A ; Holst, Bjørn ; Tümer, Zeynep ; Johnsen, Mads Grønvald ; Zhou, Shuling ; Stummann, Tina C ; Hyttel, Poul ; Clausen, Christian. / Transient p53 suppression increases reprogramming of human fibroblasts without affecting apoptosis and DNA damage. I: Stem Cell Reviews. 2014 ; Bind 3, Nr. 3. s. 404-13.

Bibtex

@article{15d9d3d4383546f580792999841a8749,
title = "Transient p53 suppression increases reprogramming of human fibroblasts without affecting apoptosis and DNA damage",
abstract = "The discovery of human-induced pluripotent stem cells (iPSCs) has sparked great interest in the potential treatment of patients with their own in vitro differentiated cells. Recently, knockout of the Tumor Protein 53 (p53) gene was reported to facilitate reprogramming but unfortunately also led to genomic instability. Here, we report that transient suppression of p53 during nonintegrative reprogramming of human fibroblasts leads to a significant increase in expression of pluripotency markers and overall number of iPSC colonies, due to downstream suppression of p21, without affecting apoptosis and DNA damage. Stable iPSC lines generated with or without p53 suppression showed comparable expression of pluripotency markers and methylation patterns, displayed normal karyotypes, contained between 0 and 5 genomic copy number variations and produced functional neurons in vitro. In conclusion, transient p53 suppression increases reprogramming efficiency without affecting genomic stability, rendering the method suitable for in vitro mechanistic studies with the possibility for future clinical translation.",
author = "Rasmussen, {Mikkel A} and Bj{\o}rn Holst and Zeynep T{\"u}mer and Johnsen, {Mads Gr{\o}nvald} and Shuling Zhou and Stummann, {Tina C} and Poul Hyttel and Christian Clausen",
note = "Copyright {\textcopyright} 2014 The Authors. Published by Elsevier Inc. All rights reserved.",
year = "2014",
month = sep,
day = "9",
doi = "10.1016/j.stemcr.2014.07.006",
language = "English",
volume = "3",
pages = "404--13",
journal = "Stem Cell Reviews and Reports",
issn = "1550-8943",
publisher = "Humana Press, Inc",
number = "3",

}

RIS

TY - JOUR

T1 - Transient p53 suppression increases reprogramming of human fibroblasts without affecting apoptosis and DNA damage

AU - Rasmussen, Mikkel A

AU - Holst, Bjørn

AU - Tümer, Zeynep

AU - Johnsen, Mads Grønvald

AU - Zhou, Shuling

AU - Stummann, Tina C

AU - Hyttel, Poul

AU - Clausen, Christian

N1 - Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.

PY - 2014/9/9

Y1 - 2014/9/9

N2 - The discovery of human-induced pluripotent stem cells (iPSCs) has sparked great interest in the potential treatment of patients with their own in vitro differentiated cells. Recently, knockout of the Tumor Protein 53 (p53) gene was reported to facilitate reprogramming but unfortunately also led to genomic instability. Here, we report that transient suppression of p53 during nonintegrative reprogramming of human fibroblasts leads to a significant increase in expression of pluripotency markers and overall number of iPSC colonies, due to downstream suppression of p21, without affecting apoptosis and DNA damage. Stable iPSC lines generated with or without p53 suppression showed comparable expression of pluripotency markers and methylation patterns, displayed normal karyotypes, contained between 0 and 5 genomic copy number variations and produced functional neurons in vitro. In conclusion, transient p53 suppression increases reprogramming efficiency without affecting genomic stability, rendering the method suitable for in vitro mechanistic studies with the possibility for future clinical translation.

AB - The discovery of human-induced pluripotent stem cells (iPSCs) has sparked great interest in the potential treatment of patients with their own in vitro differentiated cells. Recently, knockout of the Tumor Protein 53 (p53) gene was reported to facilitate reprogramming but unfortunately also led to genomic instability. Here, we report that transient suppression of p53 during nonintegrative reprogramming of human fibroblasts leads to a significant increase in expression of pluripotency markers and overall number of iPSC colonies, due to downstream suppression of p21, without affecting apoptosis and DNA damage. Stable iPSC lines generated with or without p53 suppression showed comparable expression of pluripotency markers and methylation patterns, displayed normal karyotypes, contained between 0 and 5 genomic copy number variations and produced functional neurons in vitro. In conclusion, transient p53 suppression increases reprogramming efficiency without affecting genomic stability, rendering the method suitable for in vitro mechanistic studies with the possibility for future clinical translation.

U2 - 10.1016/j.stemcr.2014.07.006

DO - 10.1016/j.stemcr.2014.07.006

M3 - Journal article

C2 - 25241739

VL - 3

SP - 404

EP - 413

JO - Stem Cell Reviews and Reports

JF - Stem Cell Reviews and Reports

SN - 1550-8943

IS - 3

ER -

ID: 44683026