Background: Undifferentiated embryonic cell transcription factor 1 (UTF1) is predominantly expressed in pluripotent stem cells and plays a vital role in embryonic development and pluripotency maintenance. Despite its established importance in murine models, the role of UTF1 on human induced pluripotent stem cells (iPSCs) has not been comprehensively studied.
Methods: This study utilized CRISPR/Cas9 gene editing to create UTF1 knockout in human fibroblasts and iPSCs.
Adult human primary dermal fibroblasts [ATCC (PCS-201-012)] were reprogrammed by transfection of oriP/EBNA-1 based episomal plasmids expressing OCT3/4, SOX2, KLF4, L-MYC, LIN28 and a p53 shRNA (Okita et al., 2011) to give rise to induced pluripotent stem cells (iPSCs). These iPSCs expressed core pluripotency markers, maintained normal karyotype, and showed tri-lineage differentiation potential.
View Article and Find Full Text PDFThe potent anti-cancer activity of naturally occurring organopolysulfides has attracted wide research attention over the last two decades. Sustained donation of hydrogen sulfide (HS) from organopolysulfides is found to be beneficial for the treatment of several organ-specific cancers. In the present study, for the first time, the mechanism of action for the potent anti-cancer activity of bis(3,5-dimethoxybenzyl) trisulfide 4 against highly aggressive triple-negative breast cancer cells (MDA-MB-231) is described.
View Article and Find Full Text PDFInduced pluripotent stem cells (iPSCs) have vast biomedical potential concerning disease modeling, drug screening and discovery, cell therapy, tissue engineering, and understanding organismal development. In the year 2006, a groundbreaking study reported the generation of iPSCs from mouse embryonic fibroblasts by viral transduction of four transcription factors, namely, Oct4, Sox2, Klf4, and c-Myc. Subsequently, human iPSCs were generated by reprogramming fibroblasts as a starting cell source using two reprogramming factor cocktails [(i) OCT4, SOX2, KLF4, and c-MYC, and (ii) OCT4, SOX2, NANOG, and LIN28].
View Article and Find Full Text PDFHuman induced Pluripotent Stem Cells (iPSCs) have enormous potential in understanding developmental biology, disease modeling, drug discovery, and regenerative medicine. The initial human iPSC studies used fibroblasts as a starting cell source to reprogram them; however, it has been identified to be a less appealing somatic cell source by numerous studies due to various reasons. One of the important criteria to achieve efficient reprogramming is determining an appropriate starting somatic cell type to induce pluripotency since the cellular source has a major influence on the reprogramming efficiency, kinetics, and quality of iPSCs.
View Article and Find Full Text PDFTranscription factor GATA4 is expressed during early embryogenesis and is vital for proper development. In addition, it is a crucial reprogramming factor for deriving functional cardiomyocytes and was recently identified as a tumor suppressor protein in various cancers. To generate a safe and effective molecular tool that can potentially be used in a cell reprogramming process and as an anti-cancer agent, we have identified optimal expression parameters to obtain soluble expression of human GATA4 in E.
View Article and Find Full Text PDFThe curiosity to understand the mechanisms regulating transcription in pluripotent cells resulted in identifying a unique transcription factor named Undifferentiated embryonic cell transcription factor 1 (UTF1). This proline-rich, nuclear protein is highly conserved among placental mammals with prominent expression observed in pluripotent, germ, and cancer cells. In pluripotent and germ cells, its role has been implicated primarily in proper cell differentiation, whereas in cancer, it shows tissue-specific function, either as an oncogene or a tumor suppressor gene.
View Article and Find Full Text PDFWe describe a novel class of stimuli-sensitive sulfonium-based synthetic lipids, which exhibit several favorable biophysical properties of phospholipids. The potent sulfonium-based lipid was successfully disassembled by glutathione to release the encapsulated drug molecules in a controlled manner. The cationic lipid also showed lower cytotoxicity against mammalian cells and displayed moderate antibacterial activities.
View Article and Find Full Text PDFDerivation of induced Pluripotent Stem Cells (iPSCs) by reprogramming somatic cells to a pluripotent state has revolutionized stem cell research. Ensuing this, various groups have used genetic and non-genetic approaches to generate iPSCs from numerous cell types. However, achieving a pluripotent state in most of the reprogramming studies is marred by serious limitations such as low reprogramming efficiency and slow kinetics.
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