In Vitro Modeling for Inherited Neurological Diseases Using Induced Pluripotent Stem Cells: From 2D to Organoid

Researchers focus on stem cell-based in vitro modeling of neurodevelopmental disorders, more specifically, the fundamentals and technical advancements in monolayer neuron and brain organoid cultures.
[Archives of Pharmacal Research]
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EGFR/FOXO3a/BIM Signaling Pathway Determines Chemosensitivity of BMP4-Differentiated Glioma Stem Cells to Temozolomide

Scientists examined whether epidermal growth factor receptor (EGFR) signaling affects bone morphogenic protein 4-induced differentiation of glioma stem cells and their response to the alkylating drug temozolomide.
[Experimental and Molecular Medicine]
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High-Throughput 3D Screening for Differentiation of hPSC-Derived Cell Therapy Candidates

Researchers demonstrated a high-throughput 3D culture platform used to systematically screen 1200 culture conditions with varying doses, durations, dynamics, and combinations of signaling cues to derive oligodendrocyte progenitor cells and midbrain dopaminergic neurons from human PSCs.
[Science Advances]
Muckom, R., Bao, X., Tran, E., Chen, E., Murugappan, A., Dordick, J. S., Clark, D. S., & Schaffer, D. V. (2020). High-throughput 3D screening for differentiation of hPSC-derived cell therapy candidates. Science Advances, 6(32), eaaz1457. https://doi.org/10.1126/sciadv.aaz1457 Cite
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Three-Dimensional Otic Neuronal Progenitor Spheroids Derived from Human Embryonic Stem Cells

Investigators generated human ESC-derived otic neuronal progenitor spheroids—an aggregate form conducive to differentiation, transplantation, and prolonged cell survival—to optimize conditions for their transplantation.
[tissue engineering]
Heuer, R. A., Nella, K. T., Chang, H.-T., Coots, K. S., Oleksijew, A. M., Roque, C. B., Silva, L. H. A., McGuire, T. L., Homma, K., & Matsuoka, A. J. (2020). Three-Dimensional Otic Neuronal Progenitor Spheroids Derived from Human Embryonic Stem Cells. Tissue Engineering Part A. https://doi.org/10.1089/ten.tea.2020.0078 Cite
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Glycolysis Links Reciprocal Activation of Myeloid Cells and Endothelial Cells in the Retinal Angiogenic Niche

Scientists showed that in the pathological angiogenic vascular niche, retinal myeloid cells, particularly macrophages/microglia that were spatially adjacent to endothelial cells, were highly glycolytic.
[Science Translational Medicine]
AbstractPress Release
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Developmental Excitation-Inhibition Imbalance Underlying Psychoses Revealed by Single-Cell Analyses of Discordant Twins-Derived Cerebral Organoids

Brain organoids derived from iPSCs of patients are a powerful avenue to investigate the pathophysiological processes. Scientists generated iPSC-derived cerebral organoids from monozygotic twins discordant for psychosis.
[Molecular Psychiatry]
Sawada, T., Chater, T. E., Sasagawa, Y., Yoshimura, M., Fujimori-Tonou, N., Tanaka, K., Benjamin, K. J. M., Paquola, A. C. M., Erwin, J. A., Goda, Y., Nikaido, I., & Kato, T. (2020). Developmental excitation-inhibition imbalance underlying psychoses revealed by single-cell analyses of discordant twins-derived cerebral organoids. Molecular Psychiatry, 1–17. https://doi.org/10.1038/s41380-020-0844-z Cite
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Mitochondrial DNA Enhance Innate Immune Responses in Neuromyelitis Optica by Monocyte Recruitment and Activation

Investigators established anti-AQP4 recombinant autoantibodies from plasmablasts in neuromyelitis optica spectrum disorder patient’s cereberospinal fluid.
[Scientific Reports]
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Functional Characterization of Three-Dimensional Cortical Cultures for In Vitro Modeling of Brain Networks

Scientists present an experimental system based on 3D scaffold-based cortical neuron cultures in which they expressed the genetically encoded calcium indicator GCaMP6f to record neuronal activity at the millimeter-scale.
[iScience]
Functional characterization of three-dimensional cortical cultures for in vitro modeling of brain networks: iScience. (n.d.). Retrieved August 6, 2020, from https://www.cell.com/iscience/fulltext/S2589-0042(20)30624-6 Cite
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Immune Phenotyping of Diverse Syngeneic Murine Brain Tumors Identifies Immunologically Distinct Types

Researchers generated distinct imageable syngeneic mouse glioblastoma-tumor models and utilized RNA-sequencing, CyTOF and correlative immunohistochemistry to assess immune-profiles in these models.
[Nature Communications]
Khalsa, J. K., Cheng, N., Keegan, J., Chaudry, A., Driver, J., Bi, W. L., Lederer, J., & Shah, K. (2020). Immune phenotyping of diverse syngeneic murine brain tumors identifies immunologically distinct types. Nature Communications, 11(1), 3912. https://doi.org/10.1038/s41467-020-17704-5 Cite
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A Widespread Neurogenic Potential of Neocortical Astrocytes Is Induced by Injury

Scientists showed that notch signaling-deficient astrocytes could generate new neurons after injury. Using single-cell RNA sequencing, they found that, when notch signaling was blocked, astrocytes transitioned to a neural stem cell-like state.
[Cell Stem Cell]
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Activation of a Neural Stem Cell Transcriptional Program in Parenchymal Astrocytes

Researchers used single-cell RNA sequencing to characterize neurogenesis by notch-depleted striatal astrocytes in vivo.
[eLife]
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