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de Majo M, Koontz M, Marsan E, Salinas N, Ramsey A, Kuo YM, Seo K, Li H, Dräger N, Leng K, Gonzales SL, Kurnellas M, Miyaoka Y, Klim JR, Kampmann M, Ward ME, Huang EJ, Ullian EM. Granulin loss of function in human mature brain organoids implicates astrocytes in TDP-43 pathology. Stem Cell Reports. 2023 Mar 14;18(3):706-719. Epub 2023 Feb 23 PubMed.
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In this study, the authors differentiated progranulin-deficient iPSCs into 3D organoids that contain both neurons and astrocytes, and observed TDP-43 pathology. Interestingly, progranulin-deficient astrocytes drive TDP-43 pathology. These observations are important, because this in-vitro experimental system recapitulates TDP-43 pathology. Hence it offers an opportunity to investigate the underlying mechanisms, in particular, the contributions of astrocytes to TDP-43 pathology found in various neurodegenerative diseases.
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