Immunity-and-Matrix-Regulatory Cells Derived from Human Embryonic Stem Cells Safely and Effectively Treat Mouse Lung Injury and Fibrosis

Intravenous delivery of immunity- and matrix-regulatory cells, derived from human embryonic stem cells, inhibited both pulmonary inflammation and fibrosis in mouse models of lung injury, and significantly improved the survival rate of the recipient mice in a dose-dependent manner, likely through paracrine regulatory mechanisms.
[Cell Research]
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Selective Induction of Human Autonomic Neurons Enables Precise Control of Cardiomyocyte Beating

Neurons were individually induced, facilitating the regulation of the beating rates of hiPSC-derived cardiomyocytes in an antagonistic manner.
[Scientific Reports]
Takayama, Y., Kushige, H., Akagi, Y., Suzuki, Y., Kumagai, Y., & Kida, Y. S. (2020). Selective Induction of Human Autonomic Neurons Enables Precise Control of Cardiomyocyte Beating. Scientific Reports, 10(1), 9464. https://doi.org/10.1038/s41598-020-66303-3 Cite
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Hair-Bearing Human Skin Generated Entirely from Pluripotent Stem Cells

Scientists report an organoid culture system that generated complex skin from human PSCs. They used stepwise modulation of the transforming growth factor β and fibroblast growth factor signaling pathways to co-induce cranial epithelial cells and neural crest cells within a spherical cell aggregate.
[Nature]
Lee, J., Rabbani, C. C., Gao, H., Steinhart, M. R., Woodruff, B. M., Pflum, Z. E., Kim, A., Heller, S., Liu, Y., Shipchandler, T. Z., & Koehler, K. R. (2020). Hair-bearing human skin generated entirely from pluripotent stem cells. Nature, 1–6. https://doi.org/10.1038/s41586-020-2352-3 Cite
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Reconstruction of the Human Blood-Brain Barrier In Vitro Reveals a Pathogenic Mechanism of APOE4 in Pericytes

Researchers revealed the role of pericytes in apolipoprotein (APOE4)-mediated cerebral amyloid angiopathy (CAA) and highlighted calcineurin-nuclear factor of activated T cells signaling as a therapeutic target in CAA and Alzheimer’s disease.
[Nature Medicine]
Blanchard, J. W., Bula, M., Davila-Velderrain, J., Akay, L. A., Zhu, L., Frank, A., Victor, M. B., Bonner, J. M., Mathys, H., Lin, Y.-T., Ko, T., Bennett, D. A., Cam, H. P., Kellis, M., & Tsai, L.-H. (2020). Reconstruction of the human blood–brain barrier in vitro reveals a pathogenic mechanism of APOE4 in pericytes. Nature Medicine, 1–12. https://doi.org/10.1038/s41591-020-0886-4 Cite
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TETs Compete with DNMT3 Activity in Pluripotent Cells at Thousands of Methylated Somatic Enhancers

Investigators analyzed the independent and combined effects of positive DNMT3A/B and negative TET1-3 regulators on the DNA methylation landscape using a panel of knockout human ESC lines.
[Nature Genetics]
Charlton, J., Jung, E. J., Mattei, A. L., Bailly, N., Liao, J., Martin, E. J., Giesselmann, P., Brändl, B., Stamenova, E. K., Müller, F.-J., Kiskinis, E., Gnirke, A., Smith, Z. D., & Meissner, A. (2020). TETs compete with DNMT3 activity in pluripotent cells at thousands of methylated somatic enhancers. Nature Genetics, 1–9. https://doi.org/10.1038/s41588-020-0639-9 Cite
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Alzheimer’s-Associated PLCγ2 Is a Signaling Node Required for Both TREM2 Function and the Inflammatory Response in Human Microglia

The authors used genetically engineered human iPSC-derived microglia-like cells to show that triggering receptor expressed on myeloid cells 2 (TREM2) signaled through PLCγ2 to mediate cell survival, phagocytosis, processing of neuronal debris, and lipid metabolism.
[Nature Neuroscience]
Andreone, B. J., Przybyla, L., Llapashtica, C., Rana, A., Davis, S. S., van Lengerich, B., Lin, K., Shi, J., Mei, Y., Astarita, G., Di Paolo, G., Sandmann, T., Monroe, K. M., & Lewcock, J. W. (2020). Alzheimer’s-associated PLCγ2 is a signaling node required for both TREM2 function and the inflammatory response in human microglia. Nature Neuroscience, 1–12. https://doi.org/10.1038/s41593-020-0650-6 Cite
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Synergistic Gene Editing in Human iPS Cells via Cell Cycle and DNA Repair Modulation

Scientists established a fluorescent DNA repair assay in human iPSCs to visualize and quantify the frequency of DNA repair outcomes during monoallelic and biallelic targeting.
[Nature Communications]
Maurissen, T. L., & Woltjen, K. (2020). Synergistic gene editing in human iPS cells via cell cycle and DNA repair modulation. Nature Communications, 11(1), 2876. https://doi.org/10.1038/s41467-020-16643-5 Cite
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N-3 Polyunsaturated Fatty Acids Promote Astrocyte Differentiation and Neurotrophin Production Independent of cAMP in Patient-Derived Neural Stem Cells

iPSC-derived neuronal stem cell lines were generated from individuals with major depressive disorder. Astrocytes differentiated from patient-derived neuronal stem cells were verified by GFAP and cells were treated with eicosapentaenoic acid, docosahexaenoic acid or stearic acid.
[Molecular Psychiatry]
Yu, J.-Z., Wang, J., Sheridan, S. D., Perlis, R. H., & Rasenick, M. M. (2020). N-3 polyunsaturated fatty acids promote astrocyte differentiation and neurotrophin production independent of cAMP in patient-derived neural stem cells. Molecular Psychiatry, 1–11. https://doi.org/10.1038/s41380-020-0786-5 Cite
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Hippo-Yap Signaling Controls Lineage Differentiation of Mouse Embryonic Stem Cells through Modulating the Formation of Super-Enhancers

Investigators found that knockout of Mst1 and Mst2, two key components of the Hippo signaling in mouse ESCs, resulted in a disruption of differentiation into mesendoderm lineage. They revealed a novel mechanism on how the Hippo-YAP signaling pathway dictated ESC lineage differentiation.
[Nucleic Acids Research]
Sun, X., Ren, Z., Cun, Y., Zhao, C., Huang, X., Zhou, J., Hu, R., Su, X., Ji, L., Li, P., Mak, K. L. K., Gao, F., Yang, Y., Xu, H., Ding, J., Cao, N., Li, S., Zhang, W., Lan, P., … Yuan, P. (n.d.). Hippo-YAP signaling controls lineage differentiation of mouse embryonic stem cells through modulating the formation of super-enhancers. Nucleic Acids Research. https://doi.org/10.1093/nar/gkaa482 Cite
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Acute Myeloid Leukemia iPSCs Reveal a Role for RUNX1 in the Maintenance of Human Leukemia Stem Cells

Researchers report that genetically clonal iPSCs derived from an acute myeloid leukemia patient and characterized by exceptionally high engraftment potential gave rise, upon hematopoietic differentiation, to a phenotypic hierarchy.
[Cell Reports]
Wesely, J., Kotini, A. G., Izzo, F., Luo, H., Yuan, H., Sun, J., Georgomanoli, M., Zviran, A., Deslauriers, A. G., Dusaj, N., Nimer, S. D., Leslie, C., Landau, D. A., Kharas, M. G., & Papapetrou, E. P. (2020). Acute Myeloid Leukemia iPSCs Reveal a Role for RUNX1 in the Maintenance of Human Leukemia Stem Cells. Cell Reports, 31(9). https://doi.org/10.1016/j.celrep.2020.107688 Cite
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Assembly and Function of a Bioengineered Human Liver for Transplantation Generated Solely from Induced Pluripotent Stem Cells

Improving methods for liver decellularization, recellularization, and differentiation of different liver cellular lineages of human iPSCs in an organ-like environment, investigators generated functional engineered human mini-livers and performed transplantation in a rat model.
[Cell Reports]
Takeishi, K., l’Hortet, A. C. de, Wang, Y., Handa, K., Guzman-Lepe, J., Matsubara, K., Morita, K., Jang, S., Haep, N., Florentino, R. M., Yuan, F., Fukumitsu, K., Tobita, K., Sun, W., Franks, J., Delgado, E. R., Shapiro, E. M., Fraunhoffer, N. A., Duncan, A. W., … Soto-Gutierrez, A. (2020). Assembly and Function of a Bioengineered Human Liver for Transplantation Generated Solely from Induced Pluripotent Stem Cells. Cell Reports, 31(9). https://doi.org/10.1016/j.celrep.2020.107711 Cite
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