Microglia-containing cerebral organoids derived from induced pluripotent stem cells for the study of neurological diseases
Summary: Microglia play an important role in neuroinflammation and neurodegeneration. Here, we report an approach for generating microglia-containing cerebral organoids derived from human pluripotent stem cells involving the supplementation of growth factors (FGF, EGF, heparin) and 10% CO2 culture c...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2023-03-01
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| Series: | iScience |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2589004223003449 |
| _version_ | 1811154752016220160 |
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| author | Yiling Hong Xu Dong Lawrence Chang Chen Xie Mariann Chang Jose S. Aguilar Jimmy Lin Juncheng Lin Qingshun Q. Li |
| author_facet | Yiling Hong Xu Dong Lawrence Chang Chen Xie Mariann Chang Jose S. Aguilar Jimmy Lin Juncheng Lin Qingshun Q. Li |
| author_sort | Yiling Hong |
| collection | DOAJ |
| description | Summary: Microglia play an important role in neuroinflammation and neurodegeneration. Here, we report an approach for generating microglia-containing cerebral organoids derived from human pluripotent stem cells involving the supplementation of growth factors (FGF, EGF, heparin) and 10% CO2 culture conditions. Using this platform, Western Pacific Amyotrophic Lateral Sclerosis and Parkinsonism–Dementia Complex (ALS-PDC) cerebral organoids were generated from patient-derived induced pluripotent stem cells (iPSCs). These ALS-PDC-affected organoids had more reactive astrocytes and M1 microglia, and had fewer M2 microglia than their unaffected counterparts, leading to impaired microglia-mediated phagocytosis. RNA-seq analysis of ALS-PDC and control organoids indicated that the most significant changes were microglia- and astrocyte-related genes (IFITM1/2, TGF-β, and GFAP). The most significantly downregulated pathway was type I interferon signaling. Interferon-gamma supplementation increased IFITM expression, enhanced microglia-mediated phagocytosis, and reduced beta-amyloid accumulation in ALS-PDC-affected network. The results demonstrated the feasibility of using microglia-containing organoids for the study of neurodegenerative diseases. |
| first_indexed | 2024-04-10T04:21:16Z |
| format | Article |
| id | doaj.art-f1826793d6c046af945c1b95aa333f33 |
| institution | Directory Open Access Journal |
| issn | 2589-0042 |
| language | English |
| last_indexed | 2024-04-10T04:21:16Z |
| publishDate | 2023-03-01 |
| publisher | Elsevier |
| record_format | Article |
| series | iScience |
| spelling | doaj.art-f1826793d6c046af945c1b95aa333f332023-03-11T04:20:17ZengElsevieriScience2589-00422023-03-01263106267Microglia-containing cerebral organoids derived from induced pluripotent stem cells for the study of neurological diseasesYiling Hong0Xu Dong1Lawrence Chang2Chen Xie3Mariann Chang4Jose S. Aguilar5Jimmy Lin6Juncheng Lin7Qingshun Q. Li8College of Veterinary Medicine, Western University of Health Sciences, Pomona, CA 91766-1854, USA; Corresponding authorGraduate College of Biomedical Sciences, Western University of Health Sciences, Pomona, CA 91766-1854, USAGraduate College of Biomedical Sciences, Western University of Health Sciences, Pomona, CA 91766-1854, USACollege of Veterinary Medicine, Western University of Health Sciences, Pomona, CA 91766-1854, USACollege of Veterinary Medicine, Western University of Health Sciences, Pomona, CA 91766-1854, USACollege of Veterinary Medicine, Western University of Health Sciences, Pomona, CA 91766-1854, USAGraduate College of Biomedical Sciences, Western University of Health Sciences, Pomona, CA 91766-1854, USAGraduate College of Biomedical Sciences, Western University of Health Sciences, Pomona, CA 91766-1854, USAGraduate College of Biomedical Sciences, Western University of Health Sciences, Pomona, CA 91766-1854, USA; Biomedical Sciences, College of Dental Medicine, Western University of Health Sciences, Pomona, CA 91766-1854, USASummary: Microglia play an important role in neuroinflammation and neurodegeneration. Here, we report an approach for generating microglia-containing cerebral organoids derived from human pluripotent stem cells involving the supplementation of growth factors (FGF, EGF, heparin) and 10% CO2 culture conditions. Using this platform, Western Pacific Amyotrophic Lateral Sclerosis and Parkinsonism–Dementia Complex (ALS-PDC) cerebral organoids were generated from patient-derived induced pluripotent stem cells (iPSCs). These ALS-PDC-affected organoids had more reactive astrocytes and M1 microglia, and had fewer M2 microglia than their unaffected counterparts, leading to impaired microglia-mediated phagocytosis. RNA-seq analysis of ALS-PDC and control organoids indicated that the most significant changes were microglia- and astrocyte-related genes (IFITM1/2, TGF-β, and GFAP). The most significantly downregulated pathway was type I interferon signaling. Interferon-gamma supplementation increased IFITM expression, enhanced microglia-mediated phagocytosis, and reduced beta-amyloid accumulation in ALS-PDC-affected network. The results demonstrated the feasibility of using microglia-containing organoids for the study of neurodegenerative diseases.http://www.sciencedirect.com/science/article/pii/S2589004223003449NeuroscienceImmunologyCell biologyStem cells research |
| spellingShingle | Yiling Hong Xu Dong Lawrence Chang Chen Xie Mariann Chang Jose S. Aguilar Jimmy Lin Juncheng Lin Qingshun Q. Li Microglia-containing cerebral organoids derived from induced pluripotent stem cells for the study of neurological diseases iScience Neuroscience Immunology Cell biology Stem cells research |
| title | Microglia-containing cerebral organoids derived from induced pluripotent stem cells for the study of neurological diseases |
| title_full | Microglia-containing cerebral organoids derived from induced pluripotent stem cells for the study of neurological diseases |
| title_fullStr | Microglia-containing cerebral organoids derived from induced pluripotent stem cells for the study of neurological diseases |
| title_full_unstemmed | Microglia-containing cerebral organoids derived from induced pluripotent stem cells for the study of neurological diseases |
| title_short | Microglia-containing cerebral organoids derived from induced pluripotent stem cells for the study of neurological diseases |
| title_sort | microglia containing cerebral organoids derived from induced pluripotent stem cells for the study of neurological diseases |
| topic | Neuroscience Immunology Cell biology Stem cells research |
| url | http://www.sciencedirect.com/science/article/pii/S2589004223003449 |
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