Reprogramming somatic cells into a pluripotent state brings patient-tailored, ethical controversy-free cellular therapy closer to reality. However, stem cells and cancer cells share many common characteristics; therefore, it is crucial to be able to discriminate between them. We generated two induced pluripotent stem cell (iPSC) lines, with NANOG pre-transduction followed by OCT3/4, SOX2, and LIN28 overexpression. One of the cell lines, CHiPS W, showed normal pluripotent stem cell characteristics, while the other, CHiPS A, though expressing pluripotency markers, failed to differentiate and gave rise to germ cell-like tumours in vivo. Comparative genomic hybridisation analysis of the generated iPS lines revealed that they were genetically more stable than human embryonic stem cell counterparts. This analysis proved to be predictive for the differentiation potential of analysed cells. Moreover, the CHiPS A line expressed a lower ratio of p53/p21 when compared to CHiPS W. NANOG pre-induction followed by OCT3/4, SOX2, MYC, and KLF4 induction resulted in the same tumour-inducing phenotype. These results underline the importance of a re-examination of the role of NANOG during reprogramming. Moreover, this reprogramming method may provide insights into primordial cell tumour formation and cancer stem cell transformation.
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http://dx.doi.org/10.22203/ecm.v022a20 | DOI Listing |
Clin Infect Dis
January 2025
Department of Cellular Therapy and Allogeneic Stem Cell Transplantation, Karolinska University Hospital Huddinge, Karolinska Comprehensive Cancer Center, Stockholm, Sweden.
Herpes simplex virus (HSV) infection is one of the most prevalent viral infections worldwide. In general, host immunity is sufficient to clear viral shedding and recurrences, although it is insufficient to prevent subsequent virologic reactivations. In immunocompromised patients, prolonged and difficult-to-treat HSV infections may develop.
View Article and Find Full Text PDFAlzheimers Dement
January 2025
Department of Neuroscience, City University of Hong Kong, Hong Kong, Hong Kong.
Introduction: Antisense oligonucleotides (ASOs) have shown promise in reducing amyloid precursor protein (APP) levels in neurons, but their effects in astrocytes, key contributors to neurodegenerative diseases, remain unclear. This study evaluates the efficacy of APP ASOs in astrocytes derived from an individual with Down syndrome (DS), a population at high risk for Alzheimer's disease (AD).
Methods: Human induced pluripotent stem cells (hiPSCs) from a healthy individual and an individual with DS were differentiated into astrocytes.
Int J Phytoremediation
January 2025
Graduate School of Environmental Studies, Tohoku University, Sendai, Japan.
ssp. is well known as a Cd hyperaccumulator. Yet, understanding how this plant survives in a high Cd environment without appearing toxicity signs is far from complete.
View Article and Find Full Text PDFHum Mol Genet
January 2025
Department of Cell & Developmental Biology, Vanderbilt University School of Medicine, 1161 21st Ave S, Nashville, Tennessee, 37232, United States of America.
Tuberous Sclerosis Complex (TSC) is a debilitating developmental disorder characterized by a variety of clinical manifestations. While benign tumors in the heart, lungs, kidney, and brain are all hallmarks of the disease, the most severe symptoms of TSC are often neurological, including seizures, autism, psychiatric disorders, and intellectual disabilities. TSC is caused by loss of function mutations in the TSC1 or TSC2 genes and consequent dysregulation of signaling via mechanistic Target of Rapamycin Complex 1 (mTORC1).
View Article and Find Full Text PDFHum Mol Genet
January 2025
Ophthalmology Department, Tongxiang First People's hospital, No. 1918 Jiaochang East Road, Tongxiang, Zhejiang 314500, China.
Activation of bone morphogenetic protein (BMP) 4 signaling promotes the survival of retinal ganglion cell (RGC) after acute injury. In this study, we investigated the role of the BMP4 signaling pathway in regulating the degeneration of retinal ganglion cells (RGCs) in a mouse glaucoma model and its potential application in retinal stem cell. Our results demonstrate that BMP4-GPX4 not only reduces oxidative stress and iron accumulation but also promotes neuroprotective factors that support the survival of transplanted RSCs into the host retina.
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