Reprogrammed keratinocytes from elderly type 2 diabetes patients suppress senescence genes to acquire induced pluripotency

Nuclear reprogramming enables patient-specific derivation of induced pluripotent stem (iPS) cells from adult tissue. Yet, iPS generation from patients with type 2 diabetes (T2D) has not been demonstrated. Here, we report reproducible iPS derivation of epidermal keratinocytes (HK) from elderly T2D pa...

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Veröffentlicht in:Aging (Albany, NY.) NY.), 2012-01, Vol.4 (1), p.60-73
Hauptverfasser: Ohmine, Seiga, Squillace, Karen A, Hartjes, Katherine A, Deeds, Michael C, Armstrong, Adam S, Thatava, Tayaramma, Sakuma, Toshie, Terzic, Andre, Kudva, Yogish, Ikeda, Yasuhiro
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container_issue 1
container_start_page 60
container_title Aging (Albany, NY.)
container_volume 4
creator Ohmine, Seiga
Squillace, Karen A
Hartjes, Katherine A
Deeds, Michael C
Armstrong, Adam S
Thatava, Tayaramma
Sakuma, Toshie
Terzic, Andre
Kudva, Yogish
Ikeda, Yasuhiro
description Nuclear reprogramming enables patient-specific derivation of induced pluripotent stem (iPS) cells from adult tissue. Yet, iPS generation from patients with type 2 diabetes (T2D) has not been demonstrated. Here, we report reproducible iPS derivation of epidermal keratinocytes (HK) from elderly T2D patients. Transduced with human OCT4, SOX2, KLF4 and c-MYC stemness factors under serum-free and feeder-free conditions, reprogrammed cells underwent dedifferentiation with mitochondrial restructuring, induction of endogenous pluripotency genes - including NANOG, LIN28, and TERT, and down-regulation of cytoskeletal, MHC class I- and apoptosis-related genes. Notably, derived iPS clones acquired a rejuvenated state, characterized by elongated telomeres and suppressed senescence-related p15INK4b/p16INK4a gene expression and oxidative stress signaling. Stepwise guidance with lineage-specifying factors, including Indolactam V and GLP-1, redifferentiated HK-derived iPS clones into insulin-producing islet-like progeny. Thus, in elderly T2D patients, reprogramming of keratinocytes ensures a senescence-privileged status yielding iPS cells proficient for regenerative applications.
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subjects Aged
Aging - genetics
Cell Culture Techniques
Diabetes Mellitus, Type 2 - metabolism
Gene Expression Profiling
Gene Expression Regulation - physiology
Genome
Humans
Insulin - metabolism
Keratinocytes - cytology
Keratinocytes - physiology
Middle Aged
Mitochondria - metabolism
Oxidative Stress
Pluripotent Stem Cells - metabolism
Research Papers
Signal Transduction
title Reprogrammed keratinocytes from elderly type 2 diabetes patients suppress senescence genes to acquire induced pluripotency
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