Multisite Studies for Validation and Improvement of a Highly Efficient Culture (HEC) Assay for Detection of Undifferentiated Human Pluripotent Stem Cells Intermingled in Cell Therapy Products

Multisite experiments confirmed that the lower limit of detection was 0.001% under various conditions to which the human iPSC lines and culture medium/substrate were subjected.
[Cytotherapy]
Watanabe, T., Yasuda, S., Kusakawa, S., Kuroda, T., Futamura, M., Ogawa, M., Mochizuki, H., Kikkawa, E., Furukawa, H., Nagaoka, M., & Sato, Y. (2020). MEASURE: Multisite studies for validation and improvement of a highly efficient culture (HEC) assay for detection of undifferentiated human pluripotent stem cells intermingled in cell therapy products. Cytotherapy, 0(0). https://doi.org/10.1016/j.jcyt.2020.07.009 Cite
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Context-Dependent Requirement of Euchromatic Histone Methyltransferase Activity during Reprogramming to Pluripotency

Scientists showed that chemical inhibition of the methyltransferases EHMT1 and EHMT2 counteracts iPSC formation in an enhanced reprogramming system in the presence of ascorbic acid, an effect that is dependent on EHMT1.
[Stem Cell Reports]
Vidal, S. E., Polyzos, A., Chatterjee, K., Ee, L., Swanzey, E., Morales-Valencia, J., Wang, H., Parikh, C. N., Amlani, B., Tu, S., Gong, Y., Snetkova, V., Skok, J. A., Tsirigos, A., Kim, S., Apostolou, E., & Stadtfeld, M. (2020). Context-Dependent Requirement of Euchromatic Histone Methyltransferase Activity during Reprogramming to Pluripotency. Stem Cell Reports, 0(0). https://doi.org/10.1016/j.stemcr.2020.08.011 Cite
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CLR01 Protects Dopaminergic Neurons In Vitro and in Mouse Models of Parkinson’s Disease

Investigators report that the molecular tweezer CLR01 decreased aggregation and toxicity in induced pluripotent stem cell-derived dopaminergic cultures treated with Parkinson’s disease brain protein extracts.
[Nature Communications]
Bengoa-Vergniory, N., Faggiani, E., Ramos-Gonzalez, P., Kirkiz, E., Connor-Robson, N., Brown, L. V., Siddique, I., Li, Z., Vingill, S., Cioroch, M., Cavaliere, F., Threlfell, S., Roberts, B., Schrader, T., Klärner, F.-G., Cragg, S., Dehay, B., Bitan, G., Matute, C., … Wade-Martins, R. (2020). CLR01 protects dopaminergic neurons in vitro and in mouse models of Parkinson’s disease. Nature Communications, 11(1), 4885. https://doi.org/10.1038/s41467-020-18689-x Cite
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Neuronal Defects in a Human Cellular Model of 22q11.2 Deletion Syndrome

Using electrophysiology and live imaging, the authors identified defects in spontaneous neuronal activity and calcium signaling in both organoid- and 2D-derived cortical neurons.
[Nature Medicine]
Khan, T. A., Revah, O., Gordon, A., Yoon, S.-J., Krawisz, A. K., Goold, C., Sun, Y., Kim, C. H., Tian, Y., Li, M.-Y., Schaepe, J. M., Ikeda, K., Amin, N. D., Sakai, N., Yazawa, M., Kushan, L., Nishino, S., Porteus, M. H., Rapoport, J. L., … Paşca, S. P. (2020). Neuronal defects in a human cellular model of 22q11.2 deletion syndrome. Nature Medicine, 1–11. https://doi.org/10.1038/s41591-020-1043-9 Cite
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Modeling the Function of BAX and BAK in Early Human Brain Development Using iPSC-Derived Systems

Scientists generated BAX/BAK double knockout human-induced pluripotent stem cells (hiPSCs), hiPSC-derived neural progenitor cells, neural rosettes, and cerebral organoids to uncover the effects of BAX and BAK deletion in an in vitro model of early human brain development.
[Cell Death & Disease]
Modeling the function of BAX and BAK in early human brain development using iPSC-derived systems | Cell Death & Disease. (n.d.). Retrieved September 25, 2020, from https://www.nature.com/articles/s41419-020-03002-x Cite
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SARS-CoV-2 Infects and Induces Cytotoxic Effects in Human Cardiomyocytes

The authors demonstrated that SARS-CoV-2 infects cardiomyocytes in vitro in an ACE2- and cathepsin-dependent manner.
[Cardiovascular Research]
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LRP6 Downregulation Promotes Cardiomyocyte Proliferation and Heart Regeneration

Researchers investigated the role of lipoprotein receptor-related protein 6 (LRP6) in heart repair through regulation of cardiomyocyte proliferation. Lrp6 deficiency increased cardiomyocyte cell cycle activity in neonatal, juvenile and adult mice.
[Cell Research]
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Upgrading the Physiological Relevance of Human Brain Organoids

The authors review recent advances in brain organoid generation and characterization with a focus on highlighting future directions utilizing interdisciplinary strategies that will be important for improving the physiological relevance of this model system.
[Neuron]
Dosso, A. D., Urenda, J.-P., Nguyen, T., & Quadrato, G. (2020). Upgrading the Physiological Relevance of Human Brain Organoids. Neuron, 107(6), 1014–1028. https://doi.org/10.1016/j.neuron.2020.08.029 Cite
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Acquired Genetic Changes in Human Pluripotent Stem Cells: Origins and Consequences

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]
Halliwell, J., Barbaric, I., & Andrews, P. W. (2020). Acquired genetic changes in human pluripotent stem cells: origins and consequences. Nature Reviews Molecular Cell Biology, 1–14. https://doi.org/10.1038/s41580-020-00292-z Cite
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Comparative Transcriptomic Analysis of Cerebral Organoids and Cortical Neuron Cultures Derived from Human Induced Pluripotent Stem Cells

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]
Kathuria, A., Lopez-Lengowski, K., Watmuff, B., & Karmacharya, R. (2020). Comparative Transcriptomic Analysis of Cerebral Organoids and Cortical Neuron Cultures Derived from Human Induced Pluripotent Stem Cells. Stem Cells and Development. https://doi.org/10.1089/scd.2020.0069 Cite
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Human Induced Pluripotent Stem Cell-Derived Lung Organoids in an Ex Vivo Model of the Congenital Diaphragmatic Hernia Fetal Lung

Researchers established a reproducible ex vivo model of lung development using transgene‐free human iPSCs generated from fetuses and infants with Bochdalek congenital diaphragmatic hernia, a polygenic disorder associated with fetal lung compression and pulmonary hypoplasia at birth.
[Stem Cells Translational Medicine]
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
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