Retroviral vectors remain the most efficient and widely applied system for induction of pluripotency. However, mutagenic effects have been documented in both laboratory and clinical gene therapy studies, principally as a result of dysregulated host gene expression in the proximity of defined integration sites. Here, we report that cells with characteristics of pluripotent stem cells can be produced from normal human fibroblasts in the absence of reprogramming transcription factors (TFs) during lentiviral (LV) vector-mediated gene transfer. This occurred via induced alterations in host gene and microRNA (miRNA) expression and detrimental changes in karyotype. These findings demonstrate that vector-induced genotoxicity may alone play a role in somatic cell reprogramming derivation and urges caution when using integrating vectors in this setting. Clearer understanding of this process may additionally reveal novel insights into reprogramming pathways.
Download full-text PDF |
Source |
---|---|
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2997595 | PMC |
http://dx.doi.org/10.1038/mt.2010.231 | DOI Listing |
Hum Exp Toxicol
January 2025
Department of Gynecology and Obstetrics, Fuyong People's Hospital, Shenzhen, China.
Gestational diabetes mellitus (GDM) is a metabolic disorder that arises during pregnancy and heightens the risk of placental dysplasia. Ginsenoside Re (Re) may stabilize insulin and glucagon to regulate glucose levels, which may improve diabetes-associated diseases. This study aims to investigate the mechanism of Re in high glucose (HG)-induced apoptosis of trophoblasts through endoplasmic reticulum stress (ERS)-related protein CHOP/GADD153.
View Article and Find Full Text PDFCell Biol Toxicol
January 2025
Department of Obstetrics and Gynecology, Shengjing Hospital of China Medical University, No. 36 Sanhao Street, Heping District, Shenyang , Liaoning Province, China.
NFKB1, a core transcription factor critical in various biological process (BP), is increasingly studied for its role in tumors. This research combines literature reviews, meta-analyses, and bioinformatics to systematically explore NFKB1's involvement in tumor initiation and progression. A unique focus is placed on the NFKB1-94 ATTG promoter polymorphism, highlighting its association with cancer risk across diverse genetic models and ethnic groups, alongside comprehensive analysis of pan-cancer expression patterns and drug sensitivity.
View Article and Find Full Text PDFFunct Integr Genomics
January 2025
School of Medical Technology, Tianjin Medical University, Tianjin, 300203, China.
Clear cell renal cell carcinoma (ccRCC) is a highly malignant tumor characterized by a significant propensity for recurrence and metastasis. DNA methylation has emerged as a critical epigenetic mechanism with substantial utility in cancer diagnosis. In this study, multi-omics data were utilized to investigate the target genes regulated by the transcription factor MYC-associated zinc finger protein (MAZ) in ccRCC, leading to the identification of thymidine phosphorylase (TYMP) as a gene with notably elevated expression in ccRCC.
View Article and Find Full Text PDFPlant Physiol
January 2025
Guizhou Engineering Research Center for Fruit Crops, Agricultural College, Guizhou University, Guiyang, Guizhou, China.
Light plays an important role in determining the L-ascorbate (AsA) pool size in plants, primarily through the transcriptional regulation of AsA metabolism-related genes. However, the specific mechanism of transcriptional induction responsible for light-dependent AsA biosynthesis remains unclear. In this study, we used a promoter sequence containing light-responsive motifs from GDP-L-galactose phosphorylase 2 (RrGGP2), a key gene involved in AsA overproduction in Rosa roxburghii fruits, to identify participating transcription factors.
View Article and Find Full Text PDFPlant Physiol
January 2025
College of Horticulture, China Agricultural University, Beijing, 100193, China.
Although C2H2 zinc finger transcription factors are important in plant growth, development, and stress resistance, their specific roles in fruit ripening have been less explored. Here, we demonstrate that the C2H2 zinc finger transcription factor 5 (SlZAT5) regulates fruit ripening in tomato (Solanum lycopersicum L.).
View Article and Find Full Text PDFEnter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!