Induced pluripotent stem cell technology: a decade of progress

Shi, Yanhong; Inoue, Haruhisa; Wu, Joseph C.; Yamanaka, Shinya

doi:10.1038/nrd.2016.245

Cited by 1,226 publications

(948 citation statements)

References 223 publications

(222 reference statements)

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“…With the discovery of induced pluripotent stem cells (iPSCs) in 2007, the past decade has flourished with new developments towards using these cells in medical applications (Shi et al, 2017). In terms of generating DA neurons, human iPSCs are very similar to hESCs in that they respond to the same differentiation cues and generate mature cells with very similar functional properties (Doi et al, 2014;Kikuchi et al, 2017;Kriks et al, 2011).…”

Section: Other Cell Types Of Interest On the Horizonmentioning

confidence: 99%

Towards stem cell based therapies for Parkinson's disease

Parmar

2018

Development

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Treating neurodegenerative diseases with cell transplantation has been within reach since the first pioneering clinical trials in which dopamine neuron progenitors from the fetal brain were transplanted to individuals with Parkinson's disease. However, the use of fetal tissue is problematic in terms of low availability and high variability, and it is also associated with ethical concerns that vary between countries. For decades, the field has therefore investigated new scalable source of therapeutic cells from stem cells or via reprogramming. Now it is possible to generate authentic midbrain dopaminergic neurons from pluripotent stem cells and clinical trials using such cells are rapidly approaching.

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Section: Other Cell Types Of Interest On the Horizonmentioning

confidence: 99%

Towards stem cell based therapies for Parkinson's disease

Parmar

2018

Development

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“…Discovery of site specific nucleases Zinc finger nuclease (ZFN), transcription activator-like effector nucleases (TALENs) along with CRISPR-Cas9 system has enhanced gene editing efficiency in iPSCs by rupturing the DNA double-strand at the site of gene modification enabling knock to in/knock out of one or more genes [93]. High system efficiency, ease of use and cheaper costs than predecessors has made CRISPR-CAS a popular editing tool.…”

Section: Gene Editing Implication In Disease Remodelingmentioning

confidence: 99%

Ips Progression a Decade Devoted

K¹

2017

J Cell Sci Ther

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Yamanaka and Takahashi's astonishing discovery in 2006 revolutionized the world of stem cells. Simplicity and reproducibility of IPSC's cells opened doors for extensive therapeutic advancements and potential clinical trials particularly in the field of Regenerative medicine. In 2012, nobel prize was presented to both researchers for the breakthrough in reprogramming somatic cells to a pluripotent state with the expression of "Yamanakas cocktail" of OKSM quartet transcription factors: sex determining region y box2 (sox2), octamer binding transcription factor4 (oct4), krupple like factor (klf4) and myelocymatosis oncogene (c-myc). Rationale of iPS use is attributed to its unlimited cell source circumventing ethical hindrance. This comprehensive review will summarize mechanisms of IPS production and cell therapy applications. Moreover, appreciate the improvements and initiatives in iPS technology, scrutinize the scientific claim of indistinguishable resemblance of iPS and eSC, evaluate the constraints during iPS manipulation and analyze safety of these pluripotent cells in clinical scenarios.

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“…This discovery holds great promise for practical applications in regenerative medicine. Gaining a greater understanding of cellular reprogramming will also provide clues about the mechanisms behind differentiation and dedifferentiation pertinent to normal development or cancer (Shi et al 2017).…”

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confidence: 99%

Coupling shRNA screens with single-cell RNA-seq identifies a dual role for mTOR in reprogramming-induced senescence

et al. 2017

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Expression of the transcription factors OCT4, SOX2, KLF4, and cMYC (OSKM) reprograms somatic cells into induced pluripotent stem cells (iPSCs). Reprogramming is a slow and inefficient process, suggesting the presence of safeguarding mechanisms that counteract cell fate conversion. One such mechanism is senescence. To identify modulators of reprogramming-induced senescence, we performed a genome-wide shRNA screen in primary human fibroblasts expressing OSKM. In the screen, we identified novel mediators of OSKM-induced senescence and validated previously implicated genes such as CDKN1A. We developed an innovative approach that integrates singlecell RNA sequencing (scRNA-seq) with the shRNA screen to investigate the mechanism of action of the identified candidates. Our data unveiled regulation of senescence as a novel way by which mechanistic target of rapamycin (mTOR) influences reprogramming. On one hand, mTOR inhibition blunts the induction of cyclin-dependent kinase (CDK) inhibitors (CDKIs), including p16 INK4a , p21 CIP1 , and p15 INK4b , preventing OSKM-induced senescence. On the other hand, inhibition of mTOR blunts the senescence-associated secretory phenotype (SASP), which itself favors reprogramming. These contrasting actions contribute to explain the complex effect that mTOR has on reprogramming. Overall, our study highlights the advantage of combining functional screens with scRNA-seq to accelerate the discovery of pathways controlling complex phenotypes.

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Induced pluripotent stem cell technology: a decade of progress

Cited by 1,226 publications

References 223 publications

Towards stem cell based therapies for Parkinson's disease

Towards stem cell based therapies for Parkinson's disease

Ips Progression a Decade Devoted

Coupling shRNA screens with single-cell RNA-seq identifies a dual role for mTOR in reprogramming-induced senescence

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