Disease-Specific Induced Pluripotent Stem Cells

Park, In Hyun; Arora, Natasha; Huo, Hongguang; Maherali, Nimet; Ahfeldt, Tim; Shimamura, Akiko; Lensch, M. William; Cowan, Chad A.; Hochedlinger, Konrad; Daley, George Q.

doi:10.1016/j.cell.2008.07.041

Cited by 2,019 publications

(1,590 citation statements)

References 32 publications

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“…Cellular models built on patient-specific iPS cells have successfully shown disease phenotypes, also when modeling psychiatric disorders (Christian et al, 2012;Park et al, 2008). The few reprogramming studies of cells from patients with psychiatric disorders have had encouraging results, proving the principle, as well as presenting possible molecular mechanisms.…”

Section: Analysesmentioning

confidence: 99%

The Roots of Autism and ADHD Twin Study in Sweden (RATSS)

et al. 2014

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Neurodevelopmental disorders affect a substantial minority of the general population. Their origins are still largely unknown, but a complex interplay of genetic and environmental factors causing disturbances of the central nervous system's maturation and a variety of higher cognitive skills is presumed. Only limited research of rather small sample size and narrow scope has been conducted in neurodevelopmental disorders using a twin-differences design. The Roots of Autism and ADHD Twin Study in Sweden (RATSS) is an ongoing project targeting monozygotic twins discordant for categorical or dimensional autistic and inattentive/hyperactive-impulsive phenotypes as well as other neurodevelopmental disorders, and typically developing twin controls. Included pairs are 9 years of age or older, and comprehensively assessed for psychopathology, medical history, neuropsychology, and dysmorphology, as well as structural, functional, and molecular brain imaging. Specimens are collected for induced pluripotent (iPS) and neuroepithelial stem cells, genetic, gut bacteria, protein-/monoamine, and electron microscopy analyses. RATSS's objective is to generate a launch pad for novel surveys to understand the complexity of genotype-environment-phenotype interactions in autism spectrum disorder and attention-deficit hyperactivity disorder (ADHD). By October 2013, RATSS had collected data from 55 twin pairs, among them 10 monozygotic pairs discordant for autism spectrum disorder, seven for ADHD, and four for other neurodevelopmental disorders. This article describes the design, recruitment, data collection, measures, collected pairs’ characteristics, as well as ongoing and planned analyses in RATSS. Potential gains of the study comprise the identification of environmentally mediated biomarkers, the emergence of candidates for drug development, translational modeling, and new leads for prevention of incapacitating outcomes.

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Section: Analysesmentioning

confidence: 99%

The Roots of Autism and ADHD Twin Study in Sweden (RATSS)

et al. 2014

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“…Disease modeling based on ESC culture is also limited for the same reason (Yamashita et al, 2006;Schneider et al, 2007;Crews et al, 2008). Strikingly, since Yamanaka's and Thomson's exciting experiments on iPSCs in 2007 (Takahashi et al, 2007;Yu et al, 2007), the successful reprogramming of fibroblasts has been accomplished for a variety of neurodegenerative and neurodevelopmental diseases, such as amyotrophic lateral sclerosis (ALS), PD (Dimos et al, 2008;Park et al, 2008;Soldner et al, 2009) Lee et al, 2009), and AD (Israel et al, 2012). The reprogramming of patient fibroblasts to human iPSCs, followed by iPSC differentiation into neurons, produces a near limitless source of live human neurons that are genetically identical to those present in patients, with which the disorder can be extensively studied.…”

Section: Modeling Of Neuronal Disorders With Nscsmentioning

confidence: 99%

“…The pathogenesis of PD is caused by the accumulation of misfolded alpha-synuclein into the intracellular Lewy bodies (Aarsland et al, 2009;Schulz-Schaeffer, 2010;Vekrellis et al, 2011) and insufficient dopamine expression in neurons in the substantia nigra of the midbrain (Goedert, 2001;Braak et al, 2007). Fibroblasts from PD patients have been successfully reprogrammed and differentiated into dopamine neurons (Park et al, 2008;Soldner et al, 2009). Strikingly, Wernig et al (2008 demonstrated that transplantation of mouse iPSC-differentiated dopamine neurons could be functionally integrated into the midbrain of PD rats.…”

Section: Modeling Of Neuronal Disorders With Nscsmentioning

confidence: 99%

Neural stem cells: mechanisms and modeling

Yao

Gage

2012

Protein Cell

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In the adult brain, neural stem cells have been found in two major niches: the hippocampus and the olfactory bulb. Neurons derived from these stem cells contribute to learning, memory, and the autonomous repair of the brain under pathological conditions. Hence, the physiology of adult neural stem cells has become a significant component of research on synaptic plasticity and neuronal disorders. In addition, the recently developed induced pluripotent stem cell technique provides a powerful tool for researchers engaged in the pathological and pharmacological study of neuronal disorders. In this review, we briefly summarize the research progress in neural stem cells in the adult brain and in the neuropathological application of the induced pluripotent stem cell technique.

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“…65,66 In the recent past, also a variety of iPS lines from single-gene disorders, chromosome syndromes and complex diseases have been generated and it would be of great interest to use iPS lines from infertile men as in vitro models for germ cell formation. 67,68 However, the spectrum of usable ES cells with an inherited defect is limited, because in vitro fertilisation with preimplantation genetic diagnosis is only rarely applied. And whereas the usage of iPS cells derived from adults has the advantage that the detailed clinical history of the patient is known, one must take into account that such cells might have already accumulated other mutations, which might then interfere with the in vitro studies on spermatogenesis.…”

Section: Amniotic Fluid Stem (Afs) Cells Could Be a Useful Tool To Stmentioning

confidence: 99%

Amniotic fluid stem cell-based models to study the effects of gene mutations and toxicants on male germ cell formation

Gundacker¹,

Dolznig²,

Mikula³

et al. 2012

Asian J Androl

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Male infertility is a major public health issue predominantly caused by defects in germ cell development. In the past, studies on the genetic regulation of spermatogenesis as well as on negative environmental impacts have been hampered by the fact that human germ cell development is intractable to direct analysis in vivo. Compared with model organisms including mice, there are fundamental differences in the molecular processes of human germ cell development. Therefore, an in vitro model mimicking human sperm formation would be an extremely valuable research tool. In the recent past, both human embryonic stem (ES) cells and induced pluripotent stem (iPS) cells have been reported to harbour the potential to differentiate into primordial germ cells and gametes. We here discuss the possibility to use human amniotic fluid stem (AFS) cells as a biological model. Since their discovery in 2003, AFS cells have been characterized to differentiate into cells of all three germ layers, to be genomically stable, to have a high proliferative potential and to be non-tumourigenic. In addition, AFS cells are not subject of ethical concerns. In contrast to iPS cells, AFSs cells do not need ectopic induction of pluripotency, which is often associated with only imperfectly cleared epigenetic memory of the source cells. Since AFS cells can be derived from amniocentesis with disease-causing mutations and can be transfected with high efficiency, they could be used in probing gene functions for spermatogenesis and in screening for male reproductive toxicity.

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Disease-Specific Induced Pluripotent Stem Cells

Cited by 2,019 publications

References 32 publications

The Roots of Autism and ADHD Twin Study in Sweden (RATSS)

The Roots of Autism and ADHD Twin Study in Sweden (RATSS)

Neural stem cells: mechanisms and modeling

Amniotic fluid stem cell-based models to study the effects of gene mutations and toxicants on male germ cell formation

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