Investigators showed proof of concept of human glial progenitor cells (hGPCs) conversion using fetal cells and also established a renewable and reproducible stem cell-based hGPC system for direct neural conversion in vitro.
[Stem Cell Reports]
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Nolbrant, S., Giacomoni, J., Hoban, D. B., Bruzelius, A., Birtele, M., Chandler-Militello, D., Pereira, M., Ottosson, D. R., Goldman, S. A., & Parmar, M. (2020). Direct Reprogramming of Human Fetal- and Stem Cell-Derived Glial Progenitor Cells into Midbrain Dopaminergic Neurons. Stem Cell Reports, 0(0). https://doi.org/10.1016/j.stemcr.2020.08.013 Cite
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.
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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
Using electrophysiology and live imaging, the authors identified defects in spontaneous neuronal activity and calcium signaling in both organoid- and 2D-derived cortical neurons.
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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
Scientists systematically investigated the expression profiles of 1,436 murine RNA-binding proteins in the developing mouse brain and identified quaking as a marker of the putative glial precursor cells population.
[Stem Cell Reports]
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Takeuchi, A., Takahashi, Y., Iida, K., Hosokawa, M., Irie, K., Ito, M., Brown, J. B., Ohno, K., Nakashima, K., & Hagiwara, M. (2020). Identification of Qk as a Glial Precursor Cell Marker that Governs the Fate Specification of Neural Stem Cells to a Glial Cell Lineage. Stem Cell Reports, 0(0). https://doi.org/10.1016/j.stemcr.2020.08.010 Cite
Researchers showed that under conditions of nutrient surplus, Upd2, a Drosophila leptin ortholog, regulated actin-based synapse reorganization to reduce bouton number in an inhibitory circuit, thus establishing a neural tone that was permissive for insulin release.
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]
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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
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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Adenoviral vectors carrying genes encoding vascular endothelial growth factor, glial cell-derived neurotrophic factor and neural cell adhesion molecule or gene engineered umbilical cord blood mononuclear cells overexpressing recombinant vascular endothelial growth factor, glial cell-derived neurotrophic factor, and neural cell adhesion molecule were intrathecally injected before distal occlusion of the middle cerebral artery in rats.
[International Journal of Molecular Sciences]
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Markosyan, V., Safiullov, Z., Izmailov, A., Fadeev, F., Sokolov, M., Kuznetsov, M., Trofimov, D., Kim, E., Kundakchyan, G., Gibadullin, A., Salafutdinov, I., Nurullin, L., Bashirov, F., & Islamov, R. (2020). Preventive Triple Gene Therapy Reduces the Negative Consequences of Ischemia-Induced Brain Injury after Modelling Stroke in a Rat. International Journal of Molecular Sciences, 21(18), 6858. https://doi.org/10.3390/ijms21186858 Cite
The authors applied a combination of translating ribosome affinity purification and ribosome profiling to identify biologically relevant prion-induced changes during disease progression in a cell-type specific and genome-wide manner. Terminally diseased mice with severe neurological symptoms showed extensive alterations in astrocytes and microglia.
Zhittya Genesis Medicine, Inc. announced that it will initiate clinical trials to test a medical hypothesis that has been advanced over the last five years that Parkinson’s disease may be caused by vascular disruption in the areas of the brain which house the “dopamine-producing neurons”, those neurons which become dysfunctional in patients suffering from this disorder.
[Zhittya Genesis Medicine, Inc. (GlobeNewswire, Inc.)]
Researchers generated induced neuronal progenitor cells from PRKN mutant patient fibroblasts with a high dopaminergic neuron yield.
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Schwartzentruber, A., Boschian, C., Lopes, F. M., Myszczynska, M. A., New, E. J., Beyrath, J., Smeitink, J., Ferraiuolo, L., & Mortiboys, H. (2020). Oxidative switch drives mitophagy defects in dopaminergic parkin mutant patient neurons. Scientific Reports, 10(1), 15485. https://doi.org/10.1038/s41598-020-72345-4 Cite