To understand transcriptomic differences in iPSC-derived monolayer neuronal cultures and 3D brain organoids, scientists differentiated eight human iPSC lines from healthy control subjects to generate cerebral organoids and cortical neuron monolayer cultures from the same set of iPSC lines.
[Stem Cells and Development]
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Researchers established a reproducible ex vivo model of lung development using transgene‐free human induced pluripotent stem cells generated from fetuses and infants with Bochdalek congenital diaphragmatic hernia (CDH), a polygenic disorder associated with fetal lung compression and pulmonary hypoplasia at birth.
[Stem Cells Translational Medicine]
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Kunisaki, S. M., Jiang, G., Biancotti, J. C., Ho, K. K. Y., Dye, B. R., Liu, A. P., & Spence, J. R. (n.d.). Human induced pluripotent stem cell-derived lung organoids in an ex vivo model of the congenital diaphragmatic hernia fetal lung. STEM CELLS Translational Medicine, n/a(n/a). https://doi.org/10.1002/sctm.20-0199 Cite
Stemson Therapeutics announced a $7.5 million seed financing led by Allergan Aesthetics, an AbbVie Company, and impact investor Fortunis Capital to advance development of Stemson’s iPSC-based technology, which is capable of producing the cell types required to initiate hair follicle growth.
[Stemson Therapeutics (Business Wire, Inc.)]
Researchers cloned TCR genes from WT1-specific CTLs regenerated from T-iPSCs, and then established WT1-TCR-iPSCs. They showed that the regenerated cytotoxic T lymphocytes from TCR-iPSCs exerted cytotoxic activity comparable to those from T-iPSCs against WT1 peptide-loaded cell line in in vitro model.
[Molecular Therapy-Methods & Clinical Development]
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Takuya, M., Nagano, S., Kashima, S., Terada, K., Agata, Y., Ichise, H., Ohtaka, M., Nakanishi, M., Fujiki, F., Sugiyama, H., Kitawaki, T., Kadowaki, N., Takaori-Kondo, A., Masuda, K., & Kawamoto, H. (2020). Regeneration of tumor antigen-specific cytotoxic T lymphocytes from iPSCs transduced with exogenous TCR genes. Molecular Therapy - Methods & Clinical Development, 0(0). https://doi.org/10.1016/j.omtm.2020.09.011 Cite
The authors discuss the types of mutations acquired by human PSCs and the mechanisms that lead to their accumulation. Recent work suggests that the underlying mutation rate in PSCs is low, although they also seem to be particularly susceptible to genomic damage.
[Nature Reviews Molecular Cell Biology]
Scientists provide a comprehensive overview on the progression of clinical trials for retinal degeneration treatment using four types of stem/progenitor cell-based transplantation to replace degenerative retinal cells and/or to supplement trophic factors from the aspects of safety, effectiveness and their respective advantages and disadvantages.
[Cell Death & Disease]
The authors further dissect mechanisms of regulatory factors clustering and transcription activation in mouse ESCs.
[Nature Structural & Molecular Biology]
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Scientists investigated the susceptibility of human iPSC-derived monolayer brain cells and region-specific brain organoids to SARS-CoV-2 infection.
[Cell Stem Cell]
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Jacob, F., Pather, S. R., Huang, W.-K., Zhang, F., Wong, S. Z. H., Zhou, H., Cubitt, B., Fan, W., Chen, C. Z., Xu, M., Pradhan, M., Zhang, D. Y., Zheng, W., Bang, A. G., Song, H., Torre, J. C. de la, & Ming, G. (2020). Human Pluripotent Stem Cell-Derived Neural Cells and Brain Organoids Reveal SARS-CoV-2 Neurotropism Predominates in Choroid Plexus Epithelium. Cell Stem Cell, 0(0). https://doi.org/10.1016/j.stem.2020.09.016 Cite
Investigators examined pluripotent, primary, differentiating, and immortalized human cells, and demonstrated that a class of origins, termed core origins, is shared by different cell types and host ~80% of all DNA replication initiation events in any cell population.
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Akerman, I., Kasaai, B., Bazarova, A., Sang, P. B., Peiffer, I., Artufel, M., Derelle, R., Smith, G., Rodriguez-Martinez, M., Romano, M., Kinet, S., Tino, P., Theillet, C., Taylor, N., Ballester, B., & Méchali, M. (2020). A predictable conserved DNA base composition signature defines human core DNA replication origins. Nature Communications, 11(1), 4826. https://doi.org/10.1038/s41467-020-18527-0 Cite
Scientists demonstrated that direct delivery of large amounts of transgene encoding guide RNA and repair template DNA via intra-ventricular injection of adeno-associated virus promotes precise targeted genome replacement in adult murine cardiomyocytes expressing Cas9.
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Kohama, Y., Higo, S., Masumura, Y., Shiba, M., Kondo, T., Ishizu, T., Higo, T., Nakamura, S., Kameda, S., Tabata, T., Inoue, H., Motooka, D., Okuzaki, D., Takashima, S., Miyagawa, S., Sawa, Y., Hikoso, S., & Sakata, Y. (2020). Adeno-associated virus-mediated gene delivery promotes S-phase entry-independent precise targeted integration in cardiomyocytes. Scientific Reports, 10(1), 15348. https://doi.org/10.1038/s41598-020-72216-y Cite
Scientists suggest that shaking culture activated TGF-β expression and Wnt signaling to promote chondrogenic differentiation in mouse iPSCs in vitro.
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