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.

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4766493PMC
http://dx.doi.org/10.1038/srep22190DOI Listing

Publication Analysis

Top Keywords

human pluripotent
16
pluripotent stem
16
stem cells
16
epigenetic silencing
8
spontaneous transformation
8
cells
7
silencing key
4
key antioxidant
4
antioxidant enzyme
4
enzyme catalase
4

Similar Publications

The MIR-NAT MAPT-AS1 does not regulate Tau expression in human neurons.

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 PDF

Depletion of TP53 in Human Pluripotent Stem Cells Triggers Malignant-Like Behavior.

Adv 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 PDF

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 PDF

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 PDF

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.

View Article and Find Full Text PDF

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!