Scientists profiled microglia differentiated from isogenic, CRISPR-modified TREM2-knockout induced pluripotent stem cell lines.
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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
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.
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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
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.
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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
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.
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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
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]
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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
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]
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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.
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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.
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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]
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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
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.
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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
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]