Induced Pluripotent Stem Cells

Publication Title: 
PloS One

Induced pluripotent stem cell (iPSC) technology can be used to model human disorders, create cell-based models of human diseases, including neurodegenerative diseases, and in establishing therapeutic strategies. To detect subtle cellular abnormalities associated with common late-onset disease in iPSCs, valid control iPSCs derived from healthy donors free of serious late-onset diseases are necessary. Here, we report the generation of iPSCs from fibroblasts obtained immediately postmortem from centenarian donors (106- and 109-years-old) who were extremely healthy until an advanced age.

Author(s): 
Yagi, Takuya
Kosakai, Arifumi
Ito, Daisuke
Okada, Yohei
Akamatsu, Wado
Nihei, Yoshihiro
Nabetani, Akira
Ishikawa, Fuyuki
Arai, Yasumichi
Hirose, Nobuyoshi
Okano, Hideyuki
Suzuki, Norihiro
Publication Title: 
Current Opinion in Cell Biology

Aging is accompanied by the functional decline of cells, tissues, and organs, as well as a striking increase in a wide range of diseases. The reprogramming of somatic cells to induced pluripotent stem cells (iPSCs) opens new avenues for the aging field and has important applications for therapeutic treatments of age-related diseases. Here we review emerging studies on how aging and age-related pathways influence iPSC generation and property.

Author(s): 
Mahmoudi, Salah
Brunet, Anne
Publication Title: 
PloS One

Induced pluripotent stem cell (iPSC) technology can be used to model human disorders, create cell-based models of human diseases, including neurodegenerative diseases, and in establishing therapeutic strategies. To detect subtle cellular abnormalities associated with common late-onset disease in iPSCs, valid control iPSCs derived from healthy donors free of serious late-onset diseases are necessary. Here, we report the generation of iPSCs from fibroblasts obtained immediately postmortem from centenarian donors (106- and 109-years-old) who were extremely healthy until an advanced age.

Author(s): 
Yagi, Takuya
Kosakai, Arifumi
Ito, Daisuke
Okada, Yohei
Akamatsu, Wado
Nihei, Yoshihiro
Nabetani, Akira
Ishikawa, Fuyuki
Arai, Yasumichi
Hirose, Nobuyoshi
Okano, Hideyuki
Suzuki, Norihiro
Publication Title: 
Current Opinion in Cell Biology

Aging is accompanied by the functional decline of cells, tissues, and organs, as well as a striking increase in a wide range of diseases. The reprogramming of somatic cells to induced pluripotent stem cells (iPSCs) opens new avenues for the aging field and has important applications for therapeutic treatments of age-related diseases. Here we review emerging studies on how aging and age-related pathways influence iPSC generation and property.

Author(s): 
Mahmoudi, Salah
Brunet, Anne
Publication Title: 
Biological Psychiatry

Nuclear transplantation, cell fusion, and induced pluripotent stem cell studies have revealed a surprising degree of plasticity in mature mammalian cell fates. Somatic cell reprogramming also has been achieved more recently by the directed conversion of nonneuronal somatic cells, such as skin fibroblasts, to neuronal phenotypes. This approach appears particularly applicable to the in vitro modeling of human neurologic disorders.

Author(s): 
Qiang, Liang
Inoue, Keiichi
Abeliovich, Asa
Publication Title: 
Biological Psychiatry

Neurodegenerative disorders of aging represent a growing public health concern. In the United States alone, there are now >5 million patients with Alzheimer's disease (AD), the most common form of dementia. No therapeutic approaches are available that alter the relentless course of AD or other dementias of aging. A major hurdle to the development of effective therapeutics has been the lack of predictive model systems in which to develop and validate candidate therapies.

Author(s): 
Doege, Claudia A.
Abeliovich, Asa
Publication Title: 
Stem Cells Translational Medicine

Recent advances in somatic cell reprogramming have highlighted the plasticity of the somatic epigenome, particularly through demonstrations of direct lineage reprogramming of adult mouse and human fibroblasts to induced pluripotent stem cells (iPSCs) and induced neurons (iNs) under defined conditions. However, human cells appear to be less plastic and have a higher epigenetic hurdle for reprogramming to both iPSCs and iNs. Here, we show that SH2B adaptor protein 1?

Author(s): 
Hsu, Yi-Chao
Chen, Su-Liang
Wang, Ya-Jean
Chen, Yun-Hsiang
Wang, Dan-Yen
Chen, Linyi
Chen, Chia-Hsiang
Chen, Hwei-Hsien
Chiu, Ing-Ming
Publication Title: 
Gene Therapy

Retroviral vectors are versatile gene transfer vehicles widely used in basic research and gene therapy. Mutation of retroviral integrase converts these vectors into transient, integration-deficient gene delivery vehicles associated with a high degree of biosafety. We explored the option to use integration-deficient retroviral vectors to achieve transient ectopic expression of transcription factors, which is considered an important tool for induced cell fate conversion.

Author(s): 
Schott, J. W.
Hoffmann, D.
Maetzig, T.
M¸ller, F.-J.
Steinemann, D.
Zychlinski, D.
Cantz, T.
Baum, C.
Schambach, A.
Publication Title: 
Stem Cell Reports

Silencing of the FMR1 gene leads to fragile X syndrome, the most common cause of inherited intellectual disability. To study the epigenetic modifications of the FMR1 gene during silencing in time, we used fibroblasts and induced pluripotent stem cells (iPSCs) of an unmethylated full mutation (uFM) individual with normal intelligence. The uFM fibroblast line carried an unmethylated FMR1 promoter region and expressed normal to slightly increased FMR1 mRNA levels.

Author(s): 
de Esch, Celine E. F.
Ghazvini, Mehrnaz
Loos, Friedemann
Schelling-Kazaryan, Nune
Widagdo, W.
Munshi, Shashini T.
van der Wal, Erik
Douben, Hannie
Gunhanlar, Nilhan
Kushner, Steven A.
Pijnappel, W. W. M. Pim
de Vrij, Femke M. S.
Geijsen, Niels
Gribnau, Joost
Willemsen, Rob
Publication Title: 
Stem Cell Reports

Induced pluripotent stem cells (iPSCs) provide an inexhaustible source of cells for modeling disease and testing drugs. Here we develop a bioinformatic approach to detect differences between the genomic programs of iPSCs derived from diseased versus normal human cohorts as they emerge during in†vitro directed differentiation. Using iPSCs generated from a cohort carrying mutations (PiZZ) in the gene responsible for alpha-1 antitrypsin (AAT) deficiency, we find that the global transcriptomes of PiZZ iPSCs diverge from normal controls upon differentiation to hepatic cells.

Author(s): 
Wilson, Andrew A.
Ying, Lei
Liesa, Marc
Segeritz, Charis-Patricia
Mills, Jason A.
Shen, Steven S.
Jean, Jyhchang
Lonza, Geordie C.
Liberti, Derek C.
Lang, Alex H.
Nazaire, Jean
Gower, Adam C.
M¸eller, Franz-Josef
Mehta, Pankaj
OrdÛÒez, Adriana
Lomas, David A.
Vallier, Ludovic
Murphy, George J.
Mostoslavsky, Gustavo
Spira, Avrum
Shirihai, Orian S.
Ramirez, Maria I.
Gadue, Paul
Kotton, Darrell N.

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