Investigators discuss the roles of the structural components of Oct proteins in reprogramming and how donor cell epigenomes endow Oct proteins with different reprogramming competences.
[Experimental & Molecular Medicine]
Scientists examined epigenome remodeling at the onset of human nuclear reprogramming by profiling human fibroblasts after fusion with murine ESCs. Efficient reprogramming of human fibroblasts to iPSCs was achieved by transduction with vectors expressing SOX2, KLF4, and inducible dnAP-1, demonstrating that dnAP-1 can substitute for exogenous human OCT4.
[Proceedings of the National Academy of Sciences of the United States of America]
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Scientists differentiated human ESCs to early cardiac mesodermal cells in microfluidic chambers that had a volume of only 30 nanoliters, using discontinuous medium perfusion. To confirm cell pluripotency, they tracked hESC proliferation and immunostained the cells for pluripotency markers SOX2 and OCT3/4.
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Using a highly parallelized approach to investigate pioneer transcription factor (PF) ability to bind methylated DNA and induce DNA demethylation, researchers showed the complex interdependence between DNA methylation and transcription factor binding; while some PFs did not affect the methylation status of their binding sites, they identified PFs that could protect DNA from methylation and others that could induce DNA demethylation at methylated binding sites.
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The authors identified a putative CSC population in immortalized and primary human ameloblastoma cells and examined possible therapeutic reagents to reduce the CSC population.
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Scientists demonstrated that local expression of the Yamanaka reprogramming factors, specifically in myofibers, induced the activation of muscle stem cells or satellite cells, which accelerated muscle regeneration in young mice.
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ALKBH5 gain- or loss-of function could effectively reverse LKB1 regulated cell proliferation, colony formation, and migration of KRAS-mutated lung cancer cells.
[Cell Death & Disease]
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Zhang, D., Ning, J., Okon, I., Zheng, X., Satyanarayana, G., Song, P., Xu, S., & Zou, M.-H. (2021). Suppression of m6A mRNA modification by DNA hypermethylated ALKBH5 aggravates the oncological behavior of KRAS mutation/LKB1 loss lung cancer. Cell Death & Disease, 12(6), 1–14. https://doi.org/10.1038/s41419-021-03793-7 Cite
The global transcriptome data of various tissues and cell lines and quantitative expression analysis of PSCs showed that ESRG expression was much higher than other human endogenous retrovirus type-Hs and tightly silenced after differentiation.
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Investigators present SFRP2 as a SOX2-antagonist with the capacity to induce a mesenchymal subtype transition in glioma cells located in vascular tumor areas, highlighting its role in glioblastoma tumor evolution and intratumoral heterogeneity.
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Researchers generated iPSCs from 3 different GS-2 patients using lentiviral vectors. The iPSCs were characterized using flow cytometry and RT-PCR and tested for the expression of pluripotency markers. In vivo differentiation to cells from all three germlines was tested using a teratoma assay. In vitro differentiation of GS-2 iPSCs into hematopoietic stem and progenitor cells was done using Op9 feeder layers and specified media.
[Stem Cell Research & Therapy]
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Scientists performed a series of studies and determined that the expression of HIF1α, HIF2α and Sox2 was decreased after hyperbaric oxygen (HBO) and that HBO promoted glioblastoma cell proliferation through cell cycle progression, albeit with a decrease in stemness, thus contributing to chemosensitization via the inhibition of HIF1α/HIF2α-Sox2.
[Cell Death Discovery]
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Wang, P., Gong, S., Pan, J., Wang, J., Zou, D., Xiong, S., Zhao, L., Yan, Q., Deng, Y., Wu, N., & Liao, B. (2021). Hyperbaric oxygen promotes not only glioblastoma proliferation but also chemosensitization by inhibiting HIF1α/HIF2α-Sox2. Cell Death Discovery, 7(1), 1–14. https://doi.org/10.1038/s41420-021-00486-0 Cite