Pluripotency and nuclear reprogramming

Yamanaka, Shinya

doi:10.1098/rstb.2008.2261

Cited by 146 publications

(87 citation statements)

References 123 publications

(137 reference statements)

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“…4C). These results are consistent with the occurrence of epigenetic remodeling during reprogramming by gene transduction (Yamanaka, 2008;Wang and Na, 2011). In addition, chromosomal G-banding analysis indicated that C1-OSN hiPSCs had a normal (46, XY) karyotype (Fig.…”

Section: Resultssupporting

confidence: 86%

A novel xeno-free and feeder-cell-free system for human pluripotent stem cell culture

et al. 2012

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While human induced pluripotent stem cells (hiPSCs) have promising applications in regenerative medicine, most of the hiPSC lines available today are not suitable for clinical applications due to contamination with nonhuman materials, such as sialic acid, and potential pathogens from animal-product-containing cell culture systems. Although several xeno-free cell culture systems have been established recently, their use of human fibroblasts as feeders reduces the clinical potential of hiPSCs due to batch-to-batch variation in the feeders and time-consuming preparation processes. In this study, we have developed a xeno-free and feeder-cell-free human embryonic stem cell (hESC)/hiPSC culture system using human plasma and human placenta extracts. The system maintains the self-renewing capacity and pluripotency of hESCs for more than 40 passages. Human iPSCs were also derived from human dermal fibroblasts using this culture system by overexpressing three transcription factors-Oct4, Sox2 and Nanog. The culture system developed here is inexpensive and suitable for large scale production.

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Section: Resultssupporting

confidence: 86%

A novel xeno-free and feeder-cell-free system for human pluripotent stem cell culture

et al. 2012

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“…Molecularly undefined reprogramming methods, such as SCNT, fusion of somatic cells with ES cells, or explantation of cells in tissue culture, use a milieu of components or elements that are largely unknown to achieve cellular reprogramming ( Fig. 1) (Hochedlinger and Jaenisch 2006;Rodolfa and Eggan 2006;Yamanaka 2008). For instance, in SCNT, undefined factors present in the oocyte cytoplasm reprogram the injected nucleus to pluripotency (e.g., transcription factors, histone-modifying and chromatin-remodeling enzymes, and DNA demethylases).…”

Section: Defining Cellular Reprogrammingmentioning

confidence: 99%

Reprogramming of Somatic Cell Identity

Hanna¹,

Carey²,

Jaenisch³

2008

Cold Spring Harbor Symposia on Quantitative Biology

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All mammalian somatic cells originate from a single fertilized cell, the zygote, and share identical genetic information despite the dramatic changes in cell structure and function that accompany organismal development. The genome is subjected to a wide array of epigenetic modifications during lineage specification, a process that contributes to the implementation and maintenance of specific gene expression programs in somatic cells. Nuclear transfer and cell-fusion experiments demonstrate that the epigenetic signature directing a cell identity can be erased and modified into that of another cell type. Furthermore, in the case of cloning, differentiated cells can be reprogrammed back to pluripotency to support the reexpression of all developmental programs. Recent breakthroughs highlight the importance of transcription factors as well as epigenetic modifiers in the establishment, maintenance, and rewiring of cell identity. By focusing on reprogramming of terminally differentiated lymphocytes, we review and highlight recent insights into the molecular mechanisms and cellular events potentially underlying programming and reprogramming of somatic cell identity in mammals.

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“…Such global changes in chromatin structure are presumed to be important for cell commitment by stabilizing gene expression programs. Committed somatic cells can be reprogrammed back to the pluripotent ESC state by forced expression of a specific set of transcription factors to create induced pluripotent stem cells (iPSCs) (4,5). However, some genes are difficult to reprogram, resulting in the generation of partially reprogrammed (p)iPSCs (6,7).…”

mentioning

confidence: 99%

Chromatin-interaction compartment switch at developmentally regulated chromosomal domains reveals an unusual principle of chromatin folding

Takebayashi

Dileep

Ryba

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

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Several 400- to 800-kb murine chromosome domains switch from early to late replication during loss of pluripotency, accompanied by a stable form of gene silencing that is resistant to reprogramming. We found that, whereas enhanced nuclease accessibility correlated with early replication genome-wide, domains that switch replication timing during differentiation were exceptionally inaccessible even when early-replicating. Nonetheless, two domains studied in detail exhibited substantial changes in transcriptional activity and higher-order chromatin unfolding confined to the region of replication timing change. Chromosome conformation capture (4C) data revealed that in the unfolded state in embryonic stem cells, these domains interacted preferentially with the early-replicating chromatin compartment, rarely interacting even with flanking late-replicating domains, whereas after differentiation, these same domains preferentially associated with late-replicating chromatin, including flanking domains. In both configurations they retained local boundaries of self-interaction, supporting the replication domain model of replication-timing regulation. Our results reveal a principle of developmentally regulated, large-scale chromosome folding involving a subnuclear compartment switch of inaccessible chromatin. This unusual level of regulation may underlie resistance to reprogramming in replication-timing switch regions.

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Pluripotency and nuclear reprogramming

Cited by 146 publications

References 123 publications

A novel xeno-free and feeder-cell-free system for human pluripotent stem cell culture

A novel xeno-free and feeder-cell-free system for human pluripotent stem cell culture

Reprogramming of Somatic Cell Identity

Chromatin-interaction compartment switch at developmentally regulated chromosomal domains reveals an unusual principle of chromatin folding

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