Brief Report: Isogenic Induced Pluripotent Stem Cell Lines From an Adult With Mosaic Down Syndrome Model Accelerated Neuronal Ageing and Neurodegeneration

Abstract Trisomy 21 (T21), Down Syndrome (DS) is the most common genetic cause of dementia and intellectual disability. Modeling DS is beginning to yield pharmaceutical therapeutic interventions for amelioration of intellectual disability, which are currently being tested in clinical trials. DS is also a unique genetic system for investigation of pathological and protective mechanisms for accelerated ageing, neurodegeneration, dementia, cancer, and other important common diseases. New drugs could be identified and disease mechanisms better understood by establishment of well‐controlled cell model systems. We have developed a first nonintegration‐reprogrammed isogenic human induced pluripotent stem cell (iPSC) model of DS by reprogramming the skin fibroblasts from an adult individual with constitutional mosaicism for DS and separately cloning multiple isogenic T21 and euploid (D21) iPSC lines. Our model shows a very low number of reprogramming rearrangements as assessed by a high‐resolution whole genome CGH‐array hybridization, and it reproduces several cellular pathologies seen in primary human DS cells, as assessed by automated high‐content microscopic analysis. Early differentiation shows an imbalance of the lineage‐specific stem/progenitor cell compartments: T21 causes slower proliferation of neural and faster expansion of hematopoietic lineage. T21 iPSC‐derived neurons show increased production of amyloid peptide‐containing material, a decrease in mitochon...
Source: Stem Cells - Category: Stem Cells Authors: Tags: Embryonic Stem Cells/Induced Pluripotent Stem Cells Source Type: research

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Source: Journal of Hazardous Materials - Category: Environmental Health Source Type: research
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Source: Expert Review of Hematology - Category: Hematology Tags: Expert Rev Hematol Source Type: research
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Source: Urology Case Reports - Category: Urology & Nephrology Source Type: research
Authors: Matti B, Zargar-Shoshtari K Abstract Prostate cancer represents a significant health burden worldwide. The cancer incidence had substantially increased since the introduction of prostate specific antigen (PSA) in cancer screening. This had led to considerable debates among health professionals and epidemiologists, since PSA as a screening tool seemed to be far from perfect. In New Zealand, the controversy was quite prominent in the last three decades, with some advocating the benefits of screening, while others concerned regarding the risk of harms. With the absence of an organised screening programme and ...
Source: New Zealand Medical Journal - Category: General Medicine Tags: N Z Med J Source Type: research
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Source: New Zealand Medical Journal - Category: General Medicine Tags: N Z Med J Source Type: research
Authors: Zarrabi A, Mark S PMID: 33032299 [PubMed - in process]
Source: New Zealand Medical Journal - Category: General Medicine Tags: N Z Med J Source Type: research
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Source: Expert Opinion on Pharmacotherapy - Category: Drugs & Pharmacology Tags: Expert Opin Pharmacother Source Type: research
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Source: Expert Opinion on Pharmacotherapy - Category: Drugs & Pharmacology Tags: Expert Opin Pharmacother Source Type: research
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Source: Fight Aging! - Category: Research Authors: Tags: Newsletters Source Type: blogs
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Source: Free Radical Biology and Medicine - Category: Biology Authors: Tags: Free Radic Biol Med Source Type: research
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