Combined negative effect of donor age and time in culture on the reprogramming efficiency into induced pluripotent stem cells

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http://hdl.handle.net/10138/216750

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Trokovic , R , Weltner , J , Noisa , P , Raivio , T & Otonkoski , T 2015 , ' Combined negative effect of donor age and time in culture on the reprogramming efficiency into induced pluripotent stem cells ' , Stem Cell Research , vol. 15 , no. 1 , pp. 254-262 . https://doi.org/10.1016/j.scr.2015.06.001

Title: Combined negative effect of donor age and time in culture on the reprogramming efficiency into induced pluripotent stem cells
Author: Trokovic, Ras; Weltner, Jere; Noisa, Parinya; Raivio, Taneli; Otonkoski, Timo
Contributor: University of Helsinki, Research Programs Unit
University of Helsinki, Research Programs Unit
University of Helsinki, Medicum
University of Helsinki, Medicum
University of Helsinki, Clinicum
Date: 2015-07
Language: eng
Number of pages: 9
Belongs to series: Stem Cell Research
ISSN: 1873-5061
URI: http://hdl.handle.net/10138/216750
Abstract: Somatic cells can be reprogrammed into induced pluripotent stem cells (iPSC) by the forced expression of the transcription factors OCT4, SOX2, KLF4 and c-MYC. Pluripotent reprogramming appears as a slow and inefficient process because of genetic and epigenetic barriers of somatic cells. In this report, we have extended previous observations concerning donor age and passage number of human fibroblasts as critical determinants of the efficiency of iPSC induction. Human fibroblasts from 11 different donors of variable age were reprogrammed by ectopic expression of reprogramming factors. Although all fibroblasts gave rise to iPSC colonies, the reprogramming efficiency correlated negatively and declined rapidly with increasing donor age. In addition, the late passage fibroblasts gave less reprogrammed colonies than the early passage cell counterparts, a finding associated with the cellular senescence-induced upregulation of p21. Knockdown of p21 restored iPSC generation even in long-term passaged fibroblasts of an old donor, highlighting the central role of the p53/p21 pathway in cellular senescence induced by both donor age and culture time. (C) 2015 The Authors. Published by Elsevier B.V.
Subject: HUMAN FIBROBLASTS
CELLULAR SENESCENCE
IPSC GENERATION
SOMATIC-CELLS
DNA-DAMAGE
P53
DIFFERENTIATION
SUPPRESSION
TELOMERES
APOPTOSIS
3111 Biomedicine
3112 Neurosciences
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