The Microfluidic Environment Reveals a Hidden Role of Self-Organizing Extracellular Matrix in Hepatic Commitment and Organoid Formation of hiPSCs

Hepatic progenitor cells either derived in microfluidics or exposed to exogenous ECM stimuli showed a significantly higher potential of forming hepatic organoids that could be rapidly expanded for several passages and further differentiated into functional hepatocytes.
[Cell Reports]
Michielin, F., Giobbe, G. G., Luni, C., Hu, Q., Maroni, I., Orford, M. R., Manfredi, A., Filippo, L. D., David, A. L., Cacchiarelli, D., Coppi, P. D., Eaton, S., & Elvassore, N. (2020). The Microfluidic Environment Reveals a Hidden Role of Self-Organizing Extracellular Matrix in Hepatic Commitment and Organoid Formation of hiPSCs. Cell Reports, 33(9). https://doi.org/10.1016/j.celrep.2020.108453 Cite
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GATA6 Regulates Aging of Human Mesenchymal Stem/Stromal Cells

Investigators reprogrammed human synovial fluid‐derived MSCs into induced pluripotent stem cells (iPSCs) using six reprogramming factors and reverted the iPSCs back to MSCs, as an approach to cell rejuvenation.
[Stem Cells]
Jiao, H., Walczak, B. E., Lee, M.-S., Lemieux, M. E., & Li, W.-J. (n.d.). GATA6 regulates aging of human mesenchymal stem/stromal cells. STEM CELLS, n/a(n/a). https://doi.org/https://doi.org/10.1002/stem.3297 Cite
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A Comprehensive Library of Human Transcription Factors for Cell Fate Engineering

Scientists demonstrated orthogonal programming by including oligodendrocyte-inducible hPSCs with unmodified hPSCs to generate cerebral organoids, which expedited in situ myelination.
[Nature Biotechnology]
Ng, A. H. M., Khoshakhlagh, P., Rojo Arias, J. E., Pasquini, G., Wang, K., Swiersy, A., Shipman, S. L., Appleton, E., Kiaee, K., Kohman, R. E., Vernet, A., Dysart, M., Leeper, K., Saylor, W., Huang, J. Y., Graveline, A., Taipale, J., Hill, D. E., Vidal, M., … Church, G. M. (2020). A comprehensive library of human transcription factors for cell fate engineering. Nature Biotechnology, 1–10. https://doi.org/10.1038/s41587-020-0742-6 Cite
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Directed Induction of Alveolar Type I Cells Derived from Pluripotent Stem Cells via Wnt Signaling Inhibition

Scientists performed single‐cell RNA sequencing of fibroblast‐dependent alveolar organoids, including human induced pluripotent stem cell‐derived epithelial cells and fetal lung fibroblasts, and identified hiPSC‐derived AT1 cells.
[Stem Cells]
Directed induction of alveolar type I cells derived from pluripotent stem cells via Wnt signaling inhibition - Kanagaki - - STEM CELLS - Wiley Online Library. (n.d.). Retrieved November 26, 2020, from https://stemcellsjournals.onlinelibrary.wiley.com/doi/10.1002/stem.3302 Cite
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Chemical Hypoxia Induces Apoptosis of Human Pluripotent Stem Cells by a NOXA-Mediated HIF-1α and HIF-2α Independent Mechanism

In order to evaluate the effect of chemically mimicked hypoxia on human PSCs cell survival, scientists analyzed changes in cell viability and several aspects of apoptosis triggered by CoCl2 and dimethyloxalylglycine.
[Scientific Reports]
Isaja, L., Mucci, S., Vera, J., Rodríguez-Varela, M. S., Marazita, M., Morris-Hanon, O., Videla-Richardson, G. A., Sevlever, G. E., Scassa, M. E., & Romorini, L. (2020). Chemical hypoxia induces apoptosis of human pluripotent stem cells by a NOXA-mediated HIF-1α and HIF-2α independent mechanism. Scientific Reports, 10(1), 20653. https://doi.org/10.1038/s41598-020-77792-7 Cite
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A Human Retinal Pigment Epithelium-Based Screening Platform Reveals Inducers of Photoreceptor Outer Segments Phagocytosis

The authors developed a high-throughput screening assay based on retinal pigment epithelium derived from human ESCs to reveal enhancers of photoreceptor outer segment phagocytosis.
[Stem Cell Reports]
Schreiter, S., Vafia, K., Barsacchi, R., Tsang, S. H., Bickle, M., Ader, M., Karl, M. O., Tanaka, E. M., & Almedawar, S. (2020). A Human Retinal Pigment Epithelium-Based Screening Platform Reveals Inducers of Photoreceptor Outer Segments Phagocytosis. Stem Cell Reports, 0(0). https://doi.org/10.1016/j.stemcr.2020.10.013 Cite
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Generation of Brain Organoids from Mouse ESCs via Teratoma Formation

Investigators aimed to establish a new method to generate brain organoids efficiently in a mouse model. They applied the in vivo teratoma formation method as a new approach to generate brain organoids.
[Stem Cell Research]
Ji Lee, W., Eon Lee, J., Ju Hong, Y., Hoon Yoon, S., Song, H., Park, C., Hong, K., Choi, Y., & Tae Do, J. (2020). Generation of brain organoids from mouse ESCs via teratoma formation. Stem Cell Research, 102100. https://doi.org/10.1016/j.scr.2020.102100 Cite
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Transformative Network Modeling of Multi-Omics Data Reveals Detailed Circuits, Key Regulators, and Potential Therapeutics for Alzheimer’s Disease

ATP6V1A was identified as a key regulator of a top-ranked neuronal subnetwork, and its role in disease-related processes was evaluated through CRISPR-based manipulation in human induced pluripotent stem cell-derived neurons and RNAi-based knockdown in Drosophila models.
[Neuron]
Wang, M., Li, A., Sekiya, M., Beckmann, N. D., Quan, X., Schrode, N., Fernando, M. B., Yu, A., Zhu, L., Cao, J., Lyu, L., Horgusluoglu, E., Wang, Q., Guo, L., Wang, Y., Neff, R., Song, W., Wang, E., Shen, Q., … Zhang, B. (2020). Transformative Network Modeling of Multi-omics Data Reveals Detailed Circuits, Key Regulators, and Potential Therapeutics for Alzheimer’s Disease. Neuron, 0(0). https://doi.org/10.1016/j.neuron.2020.11.002 Cite
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Valproate Reverses Mania-Like Behaviors in Mice via Preferential Targeting of HDAC2

Investigators employed a preclinical model to identify the therapeutic targets of valproate. They used RNA sequencing in both mice and human iPSCs derived from bipolar patients to identify important molecular targets.
[Molecular Psychiatry]
Logan, R. W., Ozburn, A. R., Arey, R. N., Ketchesin, K. D., Winquist, A., Crain, A., Tobe, B. T. D., Becker-Krail, D., Jarpe, M. B., Xue, X., Zong, W., Huo, Z., Parekh, P. K., Zhu, X., Fitzgerald, E., Zhang, H., Oliver-Smith, J., DePoy, L. M., Hildebrand, M. A., … McClung, C. A. (2020). Valproate reverses mania-like behaviors in mice via preferential targeting of HDAC2. Molecular Psychiatry, 1–19. https://doi.org/10.1038/s41380-020-00958-2 Cite
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Ntrk1 Mutation Co-Segregating with Bipolar Disorder and Inherited Kidney Disease in a Multiplex Family Causes Defects in Neuronal Growth and Depression-Like Behavior in Mice

iPSCs were generated from family members, and then differentiated to neural stem cells (NSCs). E492K NSCs had reduced neurite outgrowth. A conditional knock-in mouse line, harboring the point mutation in the brain, showed depression-like behavior in the tail suspension test following challenge by physostigmine, a cholinesterase inhibitor.
[Translational Psychiatry]
Nakajima, K., Miranda, A., Craig, D. W., Shekhtman, T., Kmoch, S., Bleyer, A., Szelinger, S., Kato, T., & Kelsoe, J. R. (2020). Ntrk1 mutation co-segregating with bipolar disorder and inherited kidney disease in a multiplex family causes defects in neuronal growth and depression-like behavior in mice. Translational Psychiatry, 10(1), 1–13. https://doi.org/10.1038/s41398-020-01087-8 Cite
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Recent Evolution of a TET-Controlled and DPPA3/STELLA-Driven Pathway of Passive DNA Demethylation in Mammals

The authors identify the mechanistic basis for the formation of genome-wide DNA hypomethylation unique to mammals. As the role of TET enzymes in active demethylation is well documented, they investigated their contribution to the hypomethylated state of naïve ESCs.
[Nature Communications]
Mulholland, C. B., Nishiyama, A., Ryan, J., Nakamura, R., Yiğit, M., Glück, I. M., Trummer, C., Qin, W., Bartoschek, M. D., Traube, F. R., Parsa, E., Ugur, E., Modic, M., Acharya, A., Stolz, P., Ziegenhain, C., Wierer, M., Enard, W., Carell, T., … Leonhardt, H. (2020). Recent evolution of a TET-controlled and DPPA3/STELLA-driven pathway of passive DNA demethylation in mammals. Nature Communications, 11(1), 5972. https://doi.org/10.1038/s41467-020-19603-1 Cite
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