Article open access publication

Transient p53 Suppression Increases Reprogramming of Human Fibroblasts without Affecting Apoptosis and DNA Damage

Stem Cell Reports, Elsevier, ISSN 2213-6711

Volume 3, 3, 2014

DOI:10.1016/j.stemcr.2014.07.006, Dimensions: pub.1052227093, PMC: PMC4266010, PMID: 25241739,

Affiliations

Organisations

  1. (1) University of Copenhagen, grid.5254.6, KU
  2. (2) Bioneer (Denmark), grid.424169.c
  3. (3) Applied Human Molecular Genetics, Kennedy Center, Copenhagen University Hospital, Rigshospitalet, Gl. Landevej 7, Glostrup 2600, Denmark
  4. (4) Lundbeck (Denmark), grid.424580.f

Countries

Denmark

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Europe

Description

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.

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University of Copenhagen

Danish Open Access Indicator

2014: Realized

Research area: Medicine

Dimensions Citation Indicators

Times Cited: 73

Field Citation Ratio (FCR): 8.8

Relative Citation ratio (RCR): 2.58

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