Scientists advocate for a paradigm shift towards the application of human iPSC-derived systems for Alzheimer’s and Parkinson’s disease modeling and the development of improved human-based models in a dish for drug discovery and preclinical assessment of therapeutic targets.
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The authors examine potential mechanisms for maintenance or shifts in heteroplasmy that occur in iPSCs generated by cellular reprogramming, and further discuss manipulations that can alter heteroplasmy to impact stem and differentiated cell performance.
[Trends in Cell Biology]
BlueRock Therapeutics, in collaboration with Memorial Sloan Kettering Cancer Center, announced that the US FDA has cleared their Investigational New Drug application to proceed with a Phase I study in patients with advanced Parkinson’s disease (PD). This is the first trial in the US to study pluripotent stem cell-derived dopaminergic neurons in patients with Parkinson’s disease.
[BlueRock Therapeutics (PR Newswire, Inc.)]
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Scientists combined bulk RNA sequencing, single cell RNA sequencing, and bioinformatic analyses, including weighted gene co-expression analysis, to investigate the gene regulatory networks regulating human iPSC differentiation under chondrogenic conditions.
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Investigators identified the role of retinal pigment epithelium (RPE) basement membrane proteins type IV collagen, laminin, and nidogen-1 in the maturation and functionality of humn ESC-RPE after cryopreservation.
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Viheriälä, T., Sorvari, J., Ihalainen, T. O., Mörö, A., Grönroos, P., Schlie-Wolter, S., Chichkov, B., Skottman, H., Nymark, S., & Ilmarinen, T. (2021). Culture surface protein coatings affect the barrier properties and calcium signalling of hESC-RPE. Scientific Reports, 11(1), 933. https://doi.org/10.1038/s41598-020-79638-8 Cite
Scientists found that the slower pace of differentiation of human neural precursors compared to that of rodents restricted induction of immune-tolerance to human antigens expressed before completion of maturation of the immune system.
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Nato, G., Corti, A., Parmigiani, E., Jachetti, E., Lecis, D., Colombo, M. P., Delia, D., Buffo, A., & Magrassi, L. (2021). Immune-tolerance to human iPS-derived neural progenitors xenografted into the immature cerebellum is overridden by species-specific differences in differentiation timing. Scientific Reports, 11(1), 651. https://doi.org/10.1038/s41598-020-79502-9 Cite
Scientists detailed an accurate, step-by-step workflow that includes in vitro microglia differentiation from human pluripotent stem cells, transplantation into the mouse brain and quantitative analysis of engraftment.
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Researchers took advantage of induced pluripotent stem cells to develop an induced human UC-derived organoid model and compared it with the induced human normal organoid model.
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Sarvestani, S. K., Signs, S., Hu, B., Yeu, Y., Feng, H., Ni, Y., Hill, D. R., Fisher, R. C., Ferrandon, S., DeHaan, R. K., Stiene, J., Cruise, M., Hwang, T. H., Shen, X., Spence, J. R., & Huang, E. H. (2021). Induced organoids derived from patients with ulcerative colitis recapitulate colitic reactivity. Nature Communications, 12(1), 262. https://doi.org/10.1038/s41467-020-20351-5 Cite
Investigators describe a protocol for the continuous patterning of hepatic, biliary and pancreatic structures from a 3D culture of human pluripotent stem cells.
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BlueRock Therapeutics, LLC. announced that the FDA has cleared their Investigational New Drug (IND) application to proceed with a Phase I study in patients with advanced Parkinson’s disease (PD). This is the first trial in the United States to study pluripotent stem cell-derived dopaminergic neurons in patients with PD.
[BlueRock Therapeutics, LLC.]
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Researchers leveraged chromatin run-on sequencing to define the landscape of active promoters, enhancers and gene bodies across distinct stages of directed differentiation of human pluripotent stem cells into small intestinal spheroids with regional specification.
[Nucleic Acids Research]
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Hung, Y.-H., Huang, S., Dame, M. K., Yu, Q., Yu, Q. C., Zeng, Y. A., Camp, J. G., Spence, J. R., & Sethupathy, P. (2021). Chromatin regulatory dynamics of early human small intestinal development using a directed differentiation model. Nucleic Acids Research, gkaa1204. https://doi.org/10.1093/nar/gkaa1204 Cite