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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Severe COVID-19 Is Marked by a Dysregulated Myeloid Cell Compartment

In a dual-center, two-cohort study, researchers combined single-cell RNA-sequencing and single-cell proteomics of whole blood and peripheral blood mononuclear cells to determine changes in immune cell composition and activation in mild vs. severe COVID-19 over time.
[Cell]
Schulte-Schrepping, J., Reusch, N., Paclik, D., Baßler, K., Schlickeiser, S., Zhang, B., Krämer, B., Krammer, T., Brumhard, S., Bonaguro, L., Domenico, E. D., Wendisch, D., Grasshoff, M., Kapellos, T. S., Beckstette, M., Pecht, T., Saglam, A., Dietrich, O., Mei, H. E., … Sander, L. E. (2020). Severe COVID-19 is marked by a dysregulated myeloid cell compartment. Cell, 0(0). https://doi.org/10.1016/j.cell.2020.08.001 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]
Zamboni, M., Llorens-Bobadilla, E., Magnusson, J. P., & Frisén, J. (2020). A Widespread Neurogenic Potential of Neocortical Astrocytes Is Induced by Injury. Cell Stem Cell, 0(0). https://doi.org/10.1016/j.stem.2020.07.006 Cite
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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]
Activation of a neural stem cell transcriptional program in parenchymal astrocytes | eLife. (n.d.). Retrieved August 5, 2020, from https://elifesciences.org/articles/59733 Cite
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Single-Cell Transcriptomics Reveals Multiple Neuronal Cell Types in Human Midbrain-Specific Organoids

Investigators demonstrated that human midbrain organoids showed essential neuronal functional properties as spontaneous electrophysiological activity of different neuronal subtypes, including dopaminergic, GABAergic, glutamatergic and serotonergic neurons.
[Cell and Tissue Research]
Smits, L. M., Magni, S., Kinugawa, K., Grzyb, K., Luginbühl, J., Sabate-Soler, S., Bolognin, S., Shin, J. W., Mori, E., Skupin, A., & Schwamborn, J. C. (2020). Single-cell transcriptomics reveals multiple neuronal cell types in human midbrain-specific organoids. Cell and Tissue Research. https://doi.org/10.1007/s00441-020-03249-y Cite
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Inflammatory Signals Induce AT2 Cell-Derived Damage-Associated Transient Progenitors that Mediate Alveolar Regeneration

The authors leveraged single-cell RNA sequencing in combination with in vivo lineage tracing and organoid models to finely map the trajectories of alveolar-lineage cells during injury repair and lung regeneration.
[Cell Stem Cell]
Choi, J., Park, J.-E., Tsagkogeorga, G., Yanagita, M., Koo, B.-K., Han, N., & Lee, J.-H. (2020). Inflammatory Signals Induce AT2 Cell-Derived Damage-Associated Transient Progenitors that Mediate Alveolar Regeneration. Cell Stem Cell, 0(0). https://doi.org/10.1016/j.stem.2020.06.020 Cite
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Expression of Amyloidogenic Transthyretin Drives Hepatic Proteostasis Remodeling in an Induced Pluripotent Stem Cell Model of Systemic Amyloid Disease

By generating an ATF6 inducible patient-specific induced pluripotent stem cell line, researchers demonstrated that enhancing hepatic ER proteostasis preferentially reduced the secretion of amyloidogenic transthyretin.
[Stem Cell Reports]
Giadone, R. M., Liberti, D. C., Matte, T. M., Rosarda, J. D., Torres-Arancivia, C., Ghosh, S., Diedrich, J. K., Pankow, S., Skvir, N., Jean, J. C., Yates, J. R., Wilson, A. A., Connors, L. H., Kotton, D. N., Wiseman, R. L., & Murphy, G. J. (2020). Expression of Amyloidogenic Transthyretin Drives Hepatic Proteostasis Remodeling in an Induced Pluripotent Stem Cell Model of Systemic Amyloid Disease. Stem Cell Reports, 0(0). https://doi.org/10.1016/j.stemcr.2020.07.003 Cite
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Cycling Stem Cells Are Radioresistant and Regenerate the Intestine

The authors demonstrate that the DNA damage-resistant Msi1+ cells are cycling intestinal stem cells that maintain and regenerate the intestinal epithelium.
[Cell Reports]
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Histone Deacetylase 3 Controls Lung Alveolar Macrophage Development and Homeostasis

Researchers showed that histone deacetylase 3 was a key epigenetic factor required for avelolar macrophage embryonic development, postnatal homeostasis, maturation, and regeneration from bone marrow.
[Nature Communications]
Yao, Y., Liu, Q., Adrianto, I., Wu, X., Glassbrook, J., Khalasawi, N., Yin, C., Yi, Q., Dong, Z., Geissmann, F., Zhou, L., & Mi, Q.-S. (2020). Histone deacetylase 3 controls lung alveolar macrophage development and homeostasis. Nature Communications, 11(1), 3822. https://doi.org/10.1038/s41467-020-17630-6 Cite
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Taming Human Brain Organoids One Cell at a Time

The authors summarize recent approaches, progresses and challenges in resolving brain organoid’s complexity through single-cell transcriptomics.
[Seminars in Cell & Developmental Biology]
Atamian, A., Cordón-Barris, L., & Quadrato, G. (2020). Taming human brain organoids one cell at a time. Seminars in Cell & Developmental Biology. https://doi.org/10.1016/j.semcdb.2020.05.022 Cite
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Single Cell Reconstruction of Human Basal Cell Diversity in Normal and IPF Lung

Researchers sought to decipher the transcriptome of freshly isolated epithelial cells from normal and idiopathic pulmonary fibrosis lung to discern disease-dependent changes within basal stem cells.
[American Journal of Respiratory and Critical Care Medicine]
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Comparative Analysis of Cell Lineage Differentiation during Hepatogenesis in Humans and Mice at the Single-Cell Transcriptome Level

Investigators performed single-cell RNA sequencing of whole human and mouse fetal livers throughout development. They identified four cell lineage families of endoderm-derived, erythroid, non-erythroid hematopoietic, and mesoderm-derived non-hematopoietic cells, and defined the developmental pathways of the major cell lineage families.
[Cell Research]
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