Epigenomic regulation is likely to be important in the maintenance of genomic integrity of human pluripotent stem cells, however, the mechanisms are unknown. We explored the epigenomes and transcriptomes of human pluripotent stem cells before and after spontaneous transformation to abnormal karyotypes and in correlation to cancer cells. Our results reveal epigenetic silencing of Catalase, a key regulator of oxidative stress and DNA damage control in abnormal cells. Our findings provide novel insight into the mechanisms associated with spontaneous transformation of human pluripotent stem cells towards malignant fate. The same mechanisms may control the genomic stability of cells in somatic tissues.
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http://dx.doi.org/10.1038/srep22190 | DOI Listing |
PLoS One
January 2025
Neuroscience Discovery, Janssen Research & Development, Janssen Pharmaceutica, Beerse, Belgium.
The MAPT gene encodes Tau protein, a member of the large family of microtubule-associated proteins. Tau forms large insoluble aggregates that are toxic to neurons in several neurological disorders, and neurofibrillary Tau tangles represent a key pathological hallmark of Alzheimer's disease (AD) and other tauopathies. Lowering Tau expression levels constitutes a potential treatment for AD but the mechanisms that regulate Tau expression at the transcriptional or translational level are not well understood.
View Article and Find Full Text PDFAdv Biol (Weinh)
January 2025
Anatomy and Physiology, Department Clinical Sciences, Faculty of Veterinary Medicine, Utrecht University, Utrecht, 3584 CL, The Netherlands.
Human pluripotent stem cells (hPSCs) tend to acquire genetic aberrations upon culture in vitro. Common aberrations are mutations in the tumor suppressor TP53, suspected to confer a growth-advantage to the mutant cells. However, their full impact in the development of malignant features and safety of hPSCs for downstream applications is yet to be elucidated.
View Article and Find Full Text PDFJ Vis Exp
December 2024
Department of Biomedical Engineering, Columbia University;
Vascular organoids derived from human induced pluripotent stem cells (hiPSCs) recapitulate the cell type diversity and complex architecture of human vascular networks. This three-dimensional (3D) model holds substantial potential for vascular pathology modeling and in vitro drug screening. Despite recent advances, a key technical challenge remains in reproducibly generating organoids with consistent quality, which is crucial for downstream assays and applications.
View Article and Find Full Text PDFRep Pract Oncol Radiother
December 2024
Department of Histology and Embryology, Poznan University of Medical Sciences, Poznan, Poland.
Background: Cancer stem cells (CSCs) constitute a small and elusive subpopulation of cancer cells within a tumor mass and are characterized by stem cell properties. Reprogrammed CSCs exhibit similar capability to initiate tumor growth, metastasis, and chemo- and radio-resistance and have similar gene profiles to primary CSCs. However, the efficiency of cancer cell reprogramming remained relatively low.
View Article and Find Full Text PDFBioact Mater
March 2025
Academy of Medical Engineering and Translational Medicine, Tianjin University, 300072, China.
The preclinical evaluation of drug-induced cardiotoxicity is critical for developing novel drug, helping to avoid drug wastage and post-marketing withdrawal. Although human induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) and the engineered heart organoid have been used for drug screening and mimicking disease models, they are always limited by the immaturity and lack of functionality of the cardiomyocytes. In this study, we constructed a Cardiomyocytes-on-a-Chip (CoC) that combines micro-grooves (MGs) and circulating mechanical stimulation to recapitulate the well-organized structure and stable beating of myocardial tissue.
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