To investigate the pathogenetic mechanisms of mitochondrial presequence processing, researchers employed cortical neurons and cerebral organoids generated from PITRM1-knockout human iPSCs.
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Pérez, M. J., Ivanyuk, D., Panagiotakopoulou, V., Di Napoli, G., Kalb, S., Brunetti, D., Al-Shaana, R., Kaeser, S. A., Fraschka, S. A.-K., Jucker, M., Zeviani, M., Viscomi, C., & Deleidi, M. (2020). Loss of function of the mitochondrial peptidase PITRM1 induces proteotoxic stress and Alzheimer’s disease-like pathology in human cerebral organoids. Molecular Psychiatry, 1–18. https://doi.org/10.1038/s41380-020-0807-4 Cite
Scientists evaluated the safety and efficacy of dopaminergic progenitors (DAPs) derived from a clinical-grade human iPSC line. They confirmed the characteristics of DAPs by in vitro analyses.
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Doi, D., Magotani, H., Kikuchi, T., Ikeda, M., Hiramatsu, S., Yoshida, K., Amano, N., Nomura, M., Umekage, M., Morizane, A., & Takahashi, J. (2020). Pre-clinical study of induced pluripotent stem cell-derived dopaminergic progenitor cells for Parkinson’s disease. Nature Communications, 11(1), 3369. https://doi.org/10.1038/s41467-020-17165-w Cite
Investigators found that polycomb repressive complex 2 (PRC2) required RNA binding for chromatin localization in human PSCs and in turn for defining cellular state.
Researchers showed that transient exposure to a single microRNA, expressed at early stages during normal development, improved the differentiation capacity of already‐established murine and human PSCs.
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Salazar-Roa, M., Trakala, M., Álvarez-Fernández, M., Valdés-Mora, F., Zhong, C., Muñoz, J., Yu, Y., Peters, T. J., Graña-Castro, O., Serrano, R., Zapatero-Solana, E., Abad, M., Bueno, M. J., de Cedrón, M. G., Fernández-Piqueras, J., Serrano, M., Blasco, M. A., Wang, D.-Z., Clark, S. J., … Malumbres, M. (2020). Transient exposure to miR-203 enhances the differentiation capacity of established pluripotent stem cells. The EMBO Journal, n/a(n/a), e104324. https://doi.org/10.15252/embj.2019104324 Cite
Investigators utilized human induced pluripotent stem cell-derived cardiomyocytes as a model to examine the mechanisms of cardiomyocyte-specific infection by SARS-CoV-2.
[Cell Reports Medicine]
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Scientists demonstrated Tfap2c was induced during the generation of iPSCs from mouse fibroblasts and acted as a facilitator for iPSCs formation. Mechanistically, the c-Myc-dependent apoptosis, a roadblock to reprogramming, can be significantly mitigated by Tfap2c overexpression.
[Cell Death & Disease]
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Wang, Y., Chen, S., Jiang, Q., Deng, J., Cheng, F., Lin, Y., Cheng, L., Ye, Y., Chen, X., Yao, Y., Zhang, X., Shi, G., Dai, L., Su, X., Peng, Y., & Deng, H. (2020). TFAP2C facilitates somatic cell reprogramming by inhibiting c-Myc -dependent apoptosis and promoting mesenchymal-to-epithelial transition. Cell Death & Disease, 11(6), 1–15. https://doi.org/10.1038/s41419-020-2684-9 Cite
Scientists presented a novel method for detecting residual undifferentiated iPSCs amongst directed differentiated cells of all three germ lineages. Marker genes, expressed specifically and highly in undifferentiated iPSC, were selected from single cell RNA sequence data to perform robust and sensitive detection of residual undifferentiated cells in differentiated cell products.
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Sekine, K., Tsuzuki, S., Yasui, R., Kobayashi, T., Ikeda, K., Hamada, Y., Kanai, E., Camp, J. G., Treutlein, B., Ueno, Y., Okamoto, S., & Taniguchi, H. (2020). Robust detection of undifferentiated iPSC among differentiated cells. Scientific Reports, 10(1), 10293. https://doi.org/10.1038/s41598-020-66845-6 Cite
Electrophysiological whole-cell voltage- and current-clamp recordings were performed on two control and three fragile X syndrome patient lines of human cortical neurons derived from iPSCs.
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Cortical neurons derived from human pluripotent stem cells lacking FMRP display altered spontaneous firing patterns | Molecular Autism | Full Text. (n.d.). Retrieved June 23, 2020, from https://molecularautism.biomedcentral.com/articles/10.1186/s13229-020-00351-4 Cite
The authors highlight the current sources for natural killer (NK) therapies and their respective constraints, discuss recent developments in the manufacturing and genetic engineering of iPSC-NK cells, and provide an overview of ongoing clinical trials using NK cells.
[Stem Cell Research & Therapy]
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Genome engineering of induced pluripotent stem cells to manufacture natural killer cell therapies | Stem Cell Research & Therapy | Full Text. (n.d.). Retrieved June 23, 2020, from https://stemcellres.biomedcentral.com/articles/10.1186/s13287-020-01741-4 Cite
Century Therapeutics has announced its acquisition of Empirica Therapeutics to leverage its iPSC-derived allogeneic cell therapies against glioblastoma.
[Businesswire (Century Therapeutics)]
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Century Therapeutics Announces Acquisition of Empirica Therapeutics. (2020, June 23). https://www.businesswire.com/news/home/20200623005319/en/Century-Therapeutics-Announces-Acquisition-Empirica-Therapeutics Cite
Inhibition of Erk1/2, tyrosine kinase, and/or GSK-3β was implied to be involved in the enhancement of the PI3K-AKT signaling pathway in the undifferentiated cells, resulting in the sustained stemness, and subsequent conversion of mouse iPSCs into cancer stem cells in the tumor microenvironment.
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Du, J., Xu, Y., Sasada, S., Oo, A. K. K., Hassan, G., Mahmud, H., Khayrani, A. C., Alam, M. J., Kumon, K., Uesaki, R., Afify, S. M., Mansour, H. M., Nair, N., Zahra, M. H., Seno, A., Okada, N., Chen, L., Yan, T., & Seno, M. (2020). Signaling Inhibitors Accelerate the Conversion of mouse iPS Cells into Cancer Stem Cells in the Tumor Microenvironment. Scientific Reports, 10(1), 9955. https://doi.org/10.1038/s41598-020-66471-2 Cite