Enhanced differentiation of neural progenitor cells in Alzheimer’s disease into vulnerable immature neurons
Summary: Focusing on the early stages of Alzheimer’s disease (AD) holds great promise. However, the specific events in neural cells preceding AD onset remain elusive. To address this, we utilized human-induced pluripotent stem cells carrying APPswe mutation to explore the initial changes associated...
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| Format: | Article |
| Language: | English |
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Elsevier
2025-05-01
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| Series: | iScience |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2589004225007072 |
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| author | Joonho Cho Simsung Bae Juyeong Jeon Janis Transfeld Changyeob Lee Alexi Nott Fan Gao Jinsoo Seo |
| author_facet | Joonho Cho Simsung Bae Juyeong Jeon Janis Transfeld Changyeob Lee Alexi Nott Fan Gao Jinsoo Seo |
| author_sort | Joonho Cho |
| collection | DOAJ |
| description | Summary: Focusing on the early stages of Alzheimer’s disease (AD) holds great promise. However, the specific events in neural cells preceding AD onset remain elusive. To address this, we utilized human-induced pluripotent stem cells carrying APPswe mutation to explore the initial changes associated with AD progression. We observed enhanced neural activity and early neuronal differentiation in APPswe cerebral organoids cultured for one month. This phenomenon was also evident when neural progenitor cells (NPCs) were differentiated into neurons. Furthermore, transcriptomic analyses of NPCs and neurons confirmed altered expression of neurogenesis-related genes in APPswe NPCs. We also found that the upregulation of reactive oxygen species (ROS) is crucial for early neuronal differentiation in these cells. In addition, APPswe neurons remained immature after initial differentiation with increased susceptibility to toxicity, providing valuable insights into the premature exit from the neural progenitor state and the increased vulnerability of neural cells in AD. |
| format | Article |
| id | doaj-art-810fb4f6ed714b2f9c7f9ac1ebf8e8d4 |
| institution | Kabale University |
| issn | 2589-0042 |
| language | English |
| publishDate | 2025-05-01 |
| publisher | Elsevier |
| record_format | Article |
| series | iScience |
| spelling | doaj-art-810fb4f6ed714b2f9c7f9ac1ebf8e8d42025-08-20T03:48:32ZengElsevieriScience2589-00422025-05-0128511244610.1016/j.isci.2025.112446Enhanced differentiation of neural progenitor cells in Alzheimer’s disease into vulnerable immature neuronsJoonho Cho0Simsung Bae1Juyeong Jeon2Janis Transfeld3Changyeob Lee4Alexi Nott5Fan Gao6Jinsoo Seo7Department of Brain Sciences, DGIST, Daegu 42988, South KoreaDepartment of Brain Sciences, DGIST, Daegu 42988, South KoreaDepartment of Brain Sciences, DGIST, Daegu 42988, South KoreaUK Dementia Research Institute at Imperial College London, London, UK; Department of Brain Sciences, Imperial College London, London, UKDepartment of Brain Sciences, DGIST, Daegu 42988, South KoreaUK Dementia Research Institute at Imperial College London, London, UK; Department of Brain Sciences, Imperial College London, London, UKBioinformatics Resource Center, Beckman Institute of Caltech, Pasadena, CA 91125, USADepartment of Brain Sciences, DGIST, Daegu 42988, South Korea; Center for Synapse Diversity and Specificity, DGIST, Daegu 42988, South Korea; Department of Systems Biology, College of Life Science and Biotechnology, Yonsei University, Seoul 03722, South Korea; Corresponding authorSummary: Focusing on the early stages of Alzheimer’s disease (AD) holds great promise. However, the specific events in neural cells preceding AD onset remain elusive. To address this, we utilized human-induced pluripotent stem cells carrying APPswe mutation to explore the initial changes associated with AD progression. We observed enhanced neural activity and early neuronal differentiation in APPswe cerebral organoids cultured for one month. This phenomenon was also evident when neural progenitor cells (NPCs) were differentiated into neurons. Furthermore, transcriptomic analyses of NPCs and neurons confirmed altered expression of neurogenesis-related genes in APPswe NPCs. We also found that the upregulation of reactive oxygen species (ROS) is crucial for early neuronal differentiation in these cells. In addition, APPswe neurons remained immature after initial differentiation with increased susceptibility to toxicity, providing valuable insights into the premature exit from the neural progenitor state and the increased vulnerability of neural cells in AD.http://www.sciencedirect.com/science/article/pii/S2589004225007072molecular biologyneurosciencecell biology |
| spellingShingle | Joonho Cho Simsung Bae Juyeong Jeon Janis Transfeld Changyeob Lee Alexi Nott Fan Gao Jinsoo Seo Enhanced differentiation of neural progenitor cells in Alzheimer’s disease into vulnerable immature neurons iScience molecular biology neuroscience cell biology |
| title | Enhanced differentiation of neural progenitor cells in Alzheimer’s disease into vulnerable immature neurons |
| title_full | Enhanced differentiation of neural progenitor cells in Alzheimer’s disease into vulnerable immature neurons |
| title_fullStr | Enhanced differentiation of neural progenitor cells in Alzheimer’s disease into vulnerable immature neurons |
| title_full_unstemmed | Enhanced differentiation of neural progenitor cells in Alzheimer’s disease into vulnerable immature neurons |
| title_short | Enhanced differentiation of neural progenitor cells in Alzheimer’s disease into vulnerable immature neurons |
| title_sort | enhanced differentiation of neural progenitor cells in alzheimer s disease into vulnerable immature neurons |
| topic | molecular biology neuroscience cell biology |
| url | http://www.sciencedirect.com/science/article/pii/S2589004225007072 |
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