Academic Journal
Generation of locus coeruleus norepinephrine neurons from human pluripotent stem cells
| العنوان: | Generation of locus coeruleus norepinephrine neurons from human pluripotent stem cells |
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| المؤلفون: | Tao, Yunlong, Li, Xueyan, Dong, Qiping, Kong, Linghai, Petersen, Andrew J., Yan, Yuanwei, Xu, Ke, Zima, Seth, Li, Yanru, Schmidt, Danielle K., Ayala, Melvin, Mathivanan, Sakthikumar, Sousa, Andre M. M., Chang, Qiang, Zhang, Su-Chun |
| المساهمون: | U.S. Department of Health & Human Services | NIH | National Institute of Neurological Disorders and Stroke, U.S. Department of Health & Human Services | NIH | Eunice Kennedy Shriver National Institute of Child Health and Human Development |
| المصدر: | Nature Biotechnology ; ISSN 1087-0156 1546-1696 |
| بيانات النشر: | Springer Science and Business Media LLC |
| سنة النشر: | 2023 |
| الوصف: | Central norepinephrine (NE) neurons, located mainly in the locus coeruleus (LC), are implicated in diverse psychiatric and neurodegenerative diseases and are an emerging target for drug discovery. To facilitate their study, we developed a method to generate 40–60% human LC-NE neurons from human pluripotent stem cells. The approach depends on our identification of ACTIVIN A in regulating LC-NE transcription factors in dorsal rhombomere 1 (r1) progenitors. In vitro generated human LC-NE neurons display extensive axonal arborization; release and uptake NE; and exhibit pacemaker activity, calcium oscillation and chemoreceptor activity in response to CO 2 . Single-nucleus RNA sequencing (snRNA-seq) analysis at multiple timepoints confirmed NE cell identity and revealed the differentiation trajectory from hindbrain progenitors to NE neurons via an ASCL1 -expressing precursor stage. LC-NE neurons engineered with an NE sensor reliably reported extracellular levels of NE. The availability of functional human LC-NE neurons enables investigation of their roles in psychiatric and neurodegenerative diseases and provides a tool for therapeutics development. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| DOI: | 10.1038/s41587-023-01977-4 |
| الاتاحة: | http://dx.doi.org/10.1038/s41587-023-01977-4 https://www.nature.com/articles/s41587-023-01977-4.pdf https://www.nature.com/articles/s41587-023-01977-4 |
| Rights: | https://creativecommons.org/licenses/by/4.0 ; https://creativecommons.org/licenses/by/4.0 |
| رقم الانضمام: | edsbas.A555B748 |
| قاعدة البيانات: | BASE |
| DOI: | 10.1038/s41587-023-01977-4 |
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