Gene Expression and Functional Deficits Underlie TREM2-Knockout Microglia Responses in Human Models of Alzheimer’s Disease

Scientists profiled microglia differentiated from isogenic, CRISPR-modified TREM2-knockout induced pluripotent stem cell lines.
[Nature Communications]
Gene expression and functional deficits underlie TREM2-knockout microglia responses in human models of Alzheimer’s disease | Nature Communications. (n.d.). Retrieved October 23, 2020, from https://www.nature.com/articles/s41467-020-19227-5 Cite
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Generation of Oligodendrocytes and Establishment of an All-Human Myelinating Platform From Human Pluripotent Stem Cells

Researchers describe a method to generate oligodendrocyte precursor cells from human pluripotent stem cells in only ~20 days, which could subsequently myelinate neurons, both in vitro and in vivo.
[Nature Protocols]
García-León, J. A., García-Díaz, B., Eggermont, K., Cáceres-Palomo, L., Neyrinck, K., Madeiro da Costa, R., Dávila, J. C., Baron-Van Evercooren, A., Gutiérrez, A., & Verfaillie, C. M. (2020). Generation of oligodendrocytes and establishment of an all-human myelinating platform from human pluripotent stem cells. Nature Protocols, 1–29. https://doi.org/10.1038/s41596-020-0395-4 Cite
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Activated Microglia Cause Metabolic Disruptions in Developmental Cortical Interneurons That Persist in Interneurons From Individuals With Schizophrenia

Researchers generated developmental cortical interneurons — which are known to be affected in schizophrenia when matured — from induced pluripotent stem cells derived from healthy controls and individuals with schizophrenia and co-cultured them with or without activated microglia.
[Nature Neuroscience]
Activated microglia cause metabolic disruptions in developmental cortical interneurons that persist in interneurons from individuals with schizophrenia | Nature Neuroscience. (n.d.). Retrieved October 23, 2020, from https://www.nature.com/articles/s41593-020-00724-1 Cite
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Herpes Simplex Virus Type 1 Infection Leads to Neurodevelopmental Disorder-Associated Neuropathological Changes

Researchers generated in vitro neurodevelopmental disorder models including human induced pluripotent stem cell based monolayer neuronal differentiation, 3D neuroepithelial bud, and 3D cerebral organoid to study fetal brain development and the potential neuropathological effects induced by the HSV-1 infections.
[Plos Pathogens]
Herpes simplex virus type 1 infection leads to neurodevelopmental disorder-associated neuropathological changes. (n.d.). Retrieved October 23, 2020, from https://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1008899 Cite
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Single-Cell RNA-Seq Reveals that CD9 Is a Negative Marker of Glucose-Responsive Pancreatic β-like Cells Derived from Human Pluripotent Stem Cells

Scientists observed more CD9+C-PEPTIDE+ β cells in the fetal than in the adult cadaveric islets and more Ki67+ proliferating cells among CD9+ fetal β cells. Their experiments showed CD9 as a cell-surface marker for negative enrichment of glucose-responsive β-like cells differentiated from human PSCs.
[Stem Cell Reports]
Li, X., Yang, K. Y., Chan, V. W., Leung, K. T., Zhang, X.-B., Wong, A. S., Chong, C. C. N., Wang, C. C., Ku, M., & Lui, K. O. (2020). Single-Cell RNA-Seq Reveals that CD9 Is a Negative Marker of Glucose-Responsive Pancreatic β-like Cells Derived from Human Pluripotent Stem Cells. Stem Cell Reports, 0(0). https://doi.org/10.1016/j.stemcr.2020.09.009 Cite
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Elimination of Mutant mtDNA by an Optimized mpTALEN Restores Differentiation Capacities of Heteroplasmic MELAS-iPSCs

Researchers refined a previously generated G13513A mtDNA-targeted platinum transcription activator-like effector nuclease (G13513A-mpTALEN) to more efficiently manipulate mtDNA heteroplasmy in mitochondrial encephalopathy, lactic acidosis, and stroke-like episodes (MELAS)-iPSCs.
[Molecular Therapy-Methods & Clinical Development]
Yahata, N., Boda, H., & Hata, R. (2020). Elimination of mutant mtDNA by an optimized mpTALEN restores differentiation capacities of heteroplasmic MELAS-iPSCs. Molecular Therapy - Methods & Clinical Development, 0(0). https://doi.org/10.1016/j.omtm.2020.10.017 Cite
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Live Visualization of ERK Activity in the Mouse Blastocyst Reveals Lineage-Specific Signaling Dynamics

To address whether differential signaling is associated with particular cell fates and states, researchers generated a targeted mouse line expressing an ERK-kinase translocation reporter that enabled live quantification of ERK activity at single-cell resolution.
[Developmental Cell]
Simon, C. S., Rahman, S., Raina, D., Schröter, C., & Hadjantonakis, A.-K. (2020). Live Visualization of ERK Activity in the Mouse Blastocyst Reveals Lineage-Specific Signaling Dynamics. Developmental Cell, 0(0). https://doi.org/10.1016/j.devcel.2020.09.030 Cite
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Cell-Cycle-Dependent ERK Signaling Dynamics Direct Fate Specification in the Mammalian Preimplantation Embryo

Endogenous tagging of Nanog in ESCs revealed that ERK inhibition promoted enhanced stabilization of NANOG protein after mitosis. Scientists showed that cell cycle, signaling, and differentiation are coordinated during preimplantation development.
[Developmental Cell]
Pokrass, M. J., Ryan, K. A., Xin, T., Pielstick, B., Timp, W., Greco, V., & Regot, S. (2020). Cell-Cycle-Dependent ERK Signaling Dynamics Direct Fate Specification in the Mammalian Preimplantation Embryo. Developmental Cell, 0(0). https://doi.org/10.1016/j.devcel.2020.09.013 Cite
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Comparison of 10 Control hPSC Lines for Drug Screening in an Engineered Heart Tissue Format

Scientists investigated ten different control hiPSC-cardiomyocyte (CM) lines and analyzed function and suitability for drug screening. Five commercial and five academic hPSC-CM lines were casted in engineered heart tissue format.
[Stem Cell Reports]
Mannhardt, I., Saleem, U., Mosqueira, D., Loos, M. F., Ulmer, B. M., Lemoine, M. D., Larsson, C., Améen, C., Korte, T. de, Vlaming, M. L. H., Harris, K., Clements, P., Denning, C., Hansen, A., & Eschenhagen, T. (2020). Comparison of 10 Control hPSC Lines for Drug Screening in an Engineered Heart Tissue Format. Stem Cell Reports, 15(4), 983–998. https://doi.org/10.1016/j.stemcr.2020.09.002 Cite
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Development and Application of High-Throughput Single Cell Lipid Profiling: A Study of SNCA-A53T Human Dopamine Neurons

The authors identified and isolated human iPSC-dopamine neurons with a TH-RFP reporter. Using liquid extraction surface analysis (LESA) coupled with high-resolution mass spectrometry they developed a high-throughput method for untargeted single cell lipid profiling.
[iScience]
Snowden, S. G., Fernandes, H. J. R., Kent, J., Foskolou, S., Tate, P., Field, S. F., Metzakopian, E., & Koulman, A. (2020). Development and application of high-throughput single cell lipid profiling: a study of SNCA-A53T human dopamine neurons. IScience, 0(0). https://doi.org/10.1016/j.isci.2020.101703 Cite
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Human Stem Cell-Derived Oligodendrocytes: From Humanized Animal Models to Cell Therapy in Myelin Diseases

The authors discuss the anatomical and functional benefit of grafted iPSC-progenitors over their brain counterparts, their use in disease modeling and the missing gaps that still prevent to study their biology in the most integrated way, and to translate iPSC-stem cell based therapy to the clinic.
[Seminars in Cell & Developmental Biology]
Mozafari, S., & Baron-Van Evercooren, A. (2020). Human stem cell-derived oligodendrocytes: From humanized animal models to cell therapy in myelin diseases. Seminars in Cell & Developmental Biology. https://doi.org/10.1016/j.semcdb.2020.09.011 Cite
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