Generation of self-organized autonomic ganglion organoids from fibroblasts
Summary: Neural organoids have been shown to serve as powerful tools for studying the mechanism of neural development and diseases as well as for screening drugs and developing cell-based therapeutics. Somatic cells have previously been reprogrammed into scattered autonomic ganglion (AG) neurons but...
| Main Authors: | , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2023-03-01
|
| Series: | iScience |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2589004223003188 |
| _version_ | 1811160168209055744 |
|---|---|
| author | Shuting Liu Kangjian Xiang Fa Yuan Mengqing Xiang |
| author_facet | Shuting Liu Kangjian Xiang Fa Yuan Mengqing Xiang |
| author_sort | Shuting Liu |
| collection | DOAJ |
| description | Summary: Neural organoids have been shown to serve as powerful tools for studying the mechanism of neural development and diseases as well as for screening drugs and developing cell-based therapeutics. Somatic cells have previously been reprogrammed into scattered autonomic ganglion (AG) neurons but not AG organoids. Here we have identified a combination of triple transcription factors (TFs) Ascl1, Phox2a/b, and Hand2 (APH) capable of efficiently reprogramming mouse fibroblasts into self-organized and networked induced AG (iAG) organoids, and characterized them by immunostaining, qRT-PCR, patch-clamping, and scRNA-seq approaches. The iAG neurons exhibit molecular properties, subtype diversity, and electrophysiological characteristics of autonomic neurons. Moreover, they can integrate into the superior cervical ganglia following transplantation and innervate and control the beating rate of co-cultured ventricular myocytes. Thus, iAG organoids may provide a valuable tool to study the pathogenesis of autonomic nervous system diseases and screen for drugs, as well as a source for cell-based therapies. |
| first_indexed | 2024-04-10T05:53:02Z |
| format | Article |
| id | doaj.art-8cfac95ede4344168711bd9d82c69c43 |
| institution | Directory Open Access Journal |
| issn | 2589-0042 |
| language | English |
| last_indexed | 2024-04-10T05:53:02Z |
| publishDate | 2023-03-01 |
| publisher | Elsevier |
| record_format | Article |
| series | iScience |
| spelling | doaj.art-8cfac95ede4344168711bd9d82c69c432023-03-04T04:23:41ZengElsevieriScience2589-00422023-03-01263106241Generation of self-organized autonomic ganglion organoids from fibroblastsShuting Liu0Kangjian Xiang1Fa Yuan2Mengqing Xiang3State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangdong Provincial Key Laboratory of Ophthalmology and Visual Science, Guangzhou 510060, China; Corresponding authorState Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangdong Provincial Key Laboratory of Ophthalmology and Visual Science, Guangzhou 510060, ChinaState Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangdong Provincial Key Laboratory of Ophthalmology and Visual Science, Guangzhou 510060, ChinaState Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangdong Provincial Key Laboratory of Ophthalmology and Visual Science, Guangzhou 510060, China; Guangdong Provincial Key Laboratory of Brain Function and Disease, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510080, China; Corresponding authorSummary: Neural organoids have been shown to serve as powerful tools for studying the mechanism of neural development and diseases as well as for screening drugs and developing cell-based therapeutics. Somatic cells have previously been reprogrammed into scattered autonomic ganglion (AG) neurons but not AG organoids. Here we have identified a combination of triple transcription factors (TFs) Ascl1, Phox2a/b, and Hand2 (APH) capable of efficiently reprogramming mouse fibroblasts into self-organized and networked induced AG (iAG) organoids, and characterized them by immunostaining, qRT-PCR, patch-clamping, and scRNA-seq approaches. The iAG neurons exhibit molecular properties, subtype diversity, and electrophysiological characteristics of autonomic neurons. Moreover, they can integrate into the superior cervical ganglia following transplantation and innervate and control the beating rate of co-cultured ventricular myocytes. Thus, iAG organoids may provide a valuable tool to study the pathogenesis of autonomic nervous system diseases and screen for drugs, as well as a source for cell-based therapies.http://www.sciencedirect.com/science/article/pii/S2589004223003188Molecular neuroscienceCellular neuroscience |
| spellingShingle | Shuting Liu Kangjian Xiang Fa Yuan Mengqing Xiang Generation of self-organized autonomic ganglion organoids from fibroblasts iScience Molecular neuroscience Cellular neuroscience |
| title | Generation of self-organized autonomic ganglion organoids from fibroblasts |
| title_full | Generation of self-organized autonomic ganglion organoids from fibroblasts |
| title_fullStr | Generation of self-organized autonomic ganglion organoids from fibroblasts |
| title_full_unstemmed | Generation of self-organized autonomic ganglion organoids from fibroblasts |
| title_short | Generation of self-organized autonomic ganglion organoids from fibroblasts |
| title_sort | generation of self organized autonomic ganglion organoids from fibroblasts |
| topic | Molecular neuroscience Cellular neuroscience |
| url | http://www.sciencedirect.com/science/article/pii/S2589004223003188 |
| work_keys_str_mv | AT shutingliu generationofselforganizedautonomicganglionorganoidsfromfibroblasts AT kangjianxiang generationofselforganizedautonomicganglionorganoidsfromfibroblasts AT fayuan generationofselforganizedautonomicganglionorganoidsfromfibroblasts AT mengqingxiang generationofselforganizedautonomicganglionorganoidsfromfibroblasts |