Induced pluripotent stem cells for modelling human diseases

Unternaehrer, Juli; Daley, George Q.

doi:10.1098/rstb.2011.0017

Cited by 71 publications

(43 citation statements)

References 45 publications

(58 reference statements)

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“…Several protocols to derive endothelial and perivascular lineages have been reported, with varying efficiencies (6)(7)(8)(9)(10)(11). Disease-specific hiPS cells may serve as an excellent source for modeling human diseases (4,12,13). Indeed, the hiPS cell-derived vascular precursor cells have been shown to be excellent models to study disease.…”

mentioning

confidence: 99%

Generation of functionally competent and durable engineered blood vessels from human induced pluripotent stem cells

Samuel

Dahéron

Liao

et al. 2013

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

138

112

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Fig. 2. Rapid induction of interchromosomal interactions by nuclear hormone signaling. (A) 3D-FISH confirmation of E 2 -induced (60 min) TFF1:GREB1 interchromosomal interactions in HMECs with the distribution of loci distances measured (box plot with scatter plot) and quantification of colocalization (bar graph) before and after E 2 treatment. Cells exhibiting mono-or biallelic interactions were combined for comparison with cells showing no colocalization; statistical significance in the bar graph was determined by χ 2 test (**, P < 0.001). (B) 2D FISH confirmation of the interchromosomal interactions in HMEC cells by combining chromosome paint (aqua) and specific DNA probes (green and red). (Upper) Illustrates two examples of mock-treated cells. (Lower) Shows the biallelic interactions/ nuclear reorganization after E 2 treatment for 60 min, exhibiting kissing events between chromosome 21 and chromosome 2. (C) Similar analysis on HMECs, but in this case using 3D FISH to paint chromosome 2 (red) and chromosome 21 (green), showing E 2 -induced chromosome 2-chromosome 21 interaction. Both assays revealed neither chromosome 21-chromosome 21 nor chromosome 2-chromosome 2 interactions in response to E 2. (D) Temporal kinetics of GREB1:TFF1 interactions by 3D FISH in HMECs (**, P < 0.001 by χ 2 ). (E-G) Nuclear microinjection of siRNA against ERα, CBP/p300, or SRC1/pCIP prevented E 2 -induced interchromosomal interactions, counting both mono-and biallelic interactions (**, P < 0.001 by χ 2 ). The injection of siER and siDLC1 were done in the same experiment, sharing the same control group. (H) Nuclear microinjection of siRNA against LSD1, which was shown to be required for estrogen-induced gene expression (22), did not block E 2 -induced interchromosomal interactions. The injection of siLSD1 and SRC1/pCIP were done in a single experiment, sharing the same control group.

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mentioning

confidence: 99%

Generation of functionally competent and durable engineered blood vessels from human induced pluripotent stem cells

Samuel

Dahéron

Liao

et al. 2013

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

138

112

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“…These pluripotent stem cells were first derived in 1998 by Thomson and colleagues from inner cell masses (ICM) of human blastocysts (13). Mechanistic studies were henceforth performed in hESCs to elucidate disease mechanisms; for instance, disease-specific hESCs can be isolated either from embryos subjected to preimplantation genetic diagnosis (PGD), or by in vitro mutagenesis of known genetic loci associated with a disease trait (14,15). Although hESCs have been generally useful in dissecting disease mechanisms (as demonstrated in Lesch-Nyhan-specific hESC lines, which successfully recapitulated the disease phenotype of increased uric acid production as a result of hypoxanthineguanine phosphoribosyltransferase (HPRT) mutations, allowing further insights into the disease mechanisms and enabling drug screening(16)), their use in ESC-based therapy has resulted in moral and ethical issues associated with the requisite blastocyst destruction.…”

Section: Cellular Reprogrammingmentioning

confidence: 99%

Cellular Reprogramming: A New Technology Frontier in Pharmaceutical Research

et al. 2011

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Induced pluripotent stem cells via cellular reprogramming are now finding multiple applications in the pharmaceutical research and drug development pipeline. In the pre-clinical stages, they serve as model systems for basic research on specific diseases and then as key experimental tools for testing and developing therapeutics. Here we examine the current state of cellular reprogramming technology, with a special emphasis on approaches that recapitulate previously intractable human diseases in vitro. We discuss the technical and operational challenges that must be tackled as reprogrammed cells become incorporated into routine pharmaceutical research and drug discovery.

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“…The ability to produce pluripotent cells from a patient's somatic cells has led to the establishment of iPS cells from many disease conditions including Parkinson's disease and amyotrophic lateral sclerosis (ALS), also known as motor neuron disease, as discussed by Unternaehrer & Daley [106] in this issue. These disease-specific iPS cells are being used in an unprecedented way to discover the molecular basis of the inherited disease and to establish assays to identify small molecules that prevent or delay the development of disease symptoms.…”

Section: Using Induced Pluripotent Stem Cells To Model Human Diseasementioning

confidence: 99%

The evolving biology of cell reprogramming

Wilmut

Sullivan²,

Chambers³

2011

Phil. Trans. R. Soc. B

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Modern stem cell biology has achieved a transformation that was thought by many to be every bit as unattainable as the ancient alchemists' dream of transforming base metals into gold. Exciting opportunities arise from the process known as ‘cellular reprogramming’ in which cells can be reliably changed from one tissue type to another. This is enabling novel approaches to more deeply investigate the fundamental basis of cell identity. In addition, new opportunities have also been created to study (perhaps even to treat) human genetic and degenerative diseases. Specific cell types that are affected in inherited disease can now be generated from easily accessible cells from the patient and compared with equivalent cells from healthy donors. The differences in cellular phenotype between the two may then be identified, and assays developed to establish therapies that prevent the development or progression of disease symptoms. Cellular reprogramming also has the potential to create new cells to replace those whose death or dysfunction causes disease symptoms. For patients suffering from inherited cases of degenerative diseases like Parkinson's disease or amyotrophic lateral sclerosis (also known as motor neuron disease), the future realization of such cell-based therapies would truly be worth its weight in gold. However, before this enormous potential can become a reality, several significant biological and technical challenges must be overcome. Furthermore, to maintain the credibility of the scientific community with the general public, it is important that hope-inspiring advances are not over-hyped. The papers in this issue of the Philosophical Transactions of the Royal Society B : Biological Sciences cover many areas relevant to this topic. In this Introduction , we provide an overall context in which to consider these individual papers.

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Induced pluripotent stem cells for modelling human diseases

Cited by 71 publications

References 45 publications

Generation of functionally competent and durable engineered blood vessels from human induced pluripotent stem cells

Generation of functionally competent and durable engineered blood vessels from human induced pluripotent stem cells

Cellular Reprogramming: A New Technology Frontier in Pharmaceutical Research

The evolving biology of cell reprogramming

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