Metabolic Reprograming via Deletion of CISH in Human iPSC-Derived NK Cells Promotes In Vivo Persistence and Enhances Anti-Tumor Activity

The authors developed human cytokine-inducible SH2-containing protein-knockout (CISH−/−) NK cells using an induced pluripotent stem cell-derived NK cell (iPSC-NK cell) platform. CISH−/− iPSC-NK cells demonstrated increased IL-15-mediated JAK-STAT signaling activity.
[Cell Stem Cell]
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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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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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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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Prevention of Tumor Risk Associated with the Reprogramming of Human Pluripotent Stem Cells

The authors focus on the risk of tumor formation by human PSCs, and on the possible treatment options if it occurs. Potential new techniques that target epigenetic processes and chromatin regulation provide opportunities for human cancer modeling and regenerative medicine.
[Journal of Experimental & Clinical Cancer Research]
Wuputra, K., Ku, C.-C., Wu, D.-C., Lin, Y.-C., Saito, S., & Yokoyama, K. K. (2020). Prevention of tumor risk associated with the reprogramming of human pluripotent stem cells. Journal of Experimental & Clinical Cancer Research, 39(1), 100. https://doi.org/10.1186/s13046-020-01584-0 Cite
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International Prize Awarded to Two Pieces of Novel Research in the 3Rs

The 2019 3Rs prize has been jointly awarded to Dr Francesca Nunn and Dr Marta Shahbazi. Marta and colleagues have developed advanced 3D cultures of human and mouse ESCs to mimic the development of the embryo at implantation and the subsequent morphogenesis and formation of the amniotic cavity.
[EurekAlert!]
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Improving the Safety of Human Pluripotent Stem Cell Therapies Using Genome-Edited Orthogonal Safeguards

Scientists used genome editing to engineer a general platform to improve the safety of future human pluripotent stem cell-derived cell transplantation therapies.
[Nature Communications]
Martin, R. M., Fowler, J. L., Cromer, M. K., Lesch, B. J., Ponce, E., Uchida, N., Nishimura, T., Porteus, M. H., & Loh, K. M. (2020). Improving the safety of human pluripotent stem cell therapies using genome-edited orthogonal safeguards. Nature Communications, 11(1), 2713. https://doi.org/10.1038/s41467-020-16455-7 Cite
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Human-iPSC-Derived Cardiac Stromal Cells Enhance Maturation in 3D Cardiac Microtissues and Reveal Non-cardiomyocyte Contributions to Heart Disease

Scientists showed that tri-cellular combinations of human induced pluripotent stem cells (iPSC)-derived cardiomyocytes, cardiac fibroblasts, and cardiac endothelial cells enhanced maturation in easily constructed, scaffold-free, three-dimensional microtissues.
[Cell Stem Cell]
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