Targeting Conserved Pathways in 3D Spheroid Formation of Diverse Cell Types for Translational Application: Enhanced Functional and Antioxidant Capacity
Three-dimensional (3D) in vitro spheroid/organoid culture increasingly appears to better mimic physiological states than standard 2D systems. The biological consequence of 3D spheroids, however, differs for different cell types: for pluripotent embryonic stem cells (ESCs), differentiation and loss o...
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| Format: | Article |
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MDPI AG
2023-08-01
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| Series: | Cells |
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| Online Access: | https://www.mdpi.com/2073-4409/12/16/2050 |
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| author | Chia-Chi Chang Shih-Sheng Jiang Fang-Yu Tsai Pei-Ju Hsu Chen-Chan Hsieh Li-Tzu Wang Men-Luh Yen B. Linju Yen |
| author_facet | Chia-Chi Chang Shih-Sheng Jiang Fang-Yu Tsai Pei-Ju Hsu Chen-Chan Hsieh Li-Tzu Wang Men-Luh Yen B. Linju Yen |
| author_sort | Chia-Chi Chang |
| collection | DOAJ |
| description | Three-dimensional (3D) in vitro spheroid/organoid culture increasingly appears to better mimic physiological states than standard 2D systems. The biological consequence of 3D spheroids, however, differs for different cell types: for pluripotent embryonic stem cells (ESCs), differentiation and loss of stemness occur, while the converse is true for somatic and cancer cells. Despite such diverse consequences, there are likely conserved mechanisms governing 3D spheroid formation across cell types that are unknown but could be efficiently targeted for translational application. To elucidate such processes, we performed transcriptome analysis with functional validation on 2D- and 3D-cultured mouse ESCs, mesenchymal stromal/stem cells (MSCs), and cancer cells. At both the transcriptomic and functional levels, 3D spheroid formation resulted in commitment towards known cell-specific functional outcomes. Surprisingly in all cell types, downregulation of the cholesterol synthesis pathway was found during 3D spheroid formation, with modulation concomitantly affecting 3D spheroid formation and cell-specific consequences; similar results were seen with human cell types. Furthermore, improved antioxidant capacity after 3D spheroid formation across cell types was further enhanced with modulation of the pathway. These findings demonstrate the profound cell-specific consequences and the translational value of understanding conserved mechanisms across diverse cell types after 3D spheroid formation. |
| first_indexed | 2024-03-11T00:03:35Z |
| format | Article |
| id | doaj.art-a061d485acd244bcbe966e468b6c785b |
| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-11T00:03:35Z |
| publishDate | 2023-08-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cells |
| spelling | doaj.art-a061d485acd244bcbe966e468b6c785b2023-11-19T00:36:42ZengMDPI AGCells2073-44092023-08-011216205010.3390/cells12162050Targeting Conserved Pathways in 3D Spheroid Formation of Diverse Cell Types for Translational Application: Enhanced Functional and Antioxidant CapacityChia-Chi Chang0Shih-Sheng Jiang1Fang-Yu Tsai2Pei-Ju Hsu3Chen-Chan Hsieh4Li-Tzu Wang5Men-Luh Yen6B. Linju Yen7Graduate Institute of Life Sciences, National Defense Medical Center (NDMC), Taipei 114, TaiwanNational Institute of Cancer Research, NHRI, Zhunan 350, TaiwanNational Institute of Cancer Research, NHRI, Zhunan 350, TaiwanRegenerative Medicine Research Group, Institute of Cellular & System Medicine, National Health Research Institutes (NHRI), Zhunan 350, TaiwanRegenerative Medicine Research Group, Institute of Cellular & System Medicine, National Health Research Institutes (NHRI), Zhunan 350, TaiwanDepartment of Obstetrics/Gynecology, National Taiwan University (NTU) Hospital & College of Medicine, Taipei 100, TaiwanDepartment of Obstetrics/Gynecology, National Taiwan University (NTU) Hospital & College of Medicine, Taipei 100, TaiwanGraduate Institute of Life Sciences, National Defense Medical Center (NDMC), Taipei 114, TaiwanThree-dimensional (3D) in vitro spheroid/organoid culture increasingly appears to better mimic physiological states than standard 2D systems. The biological consequence of 3D spheroids, however, differs for different cell types: for pluripotent embryonic stem cells (ESCs), differentiation and loss of stemness occur, while the converse is true for somatic and cancer cells. Despite such diverse consequences, there are likely conserved mechanisms governing 3D spheroid formation across cell types that are unknown but could be efficiently targeted for translational application. To elucidate such processes, we performed transcriptome analysis with functional validation on 2D- and 3D-cultured mouse ESCs, mesenchymal stromal/stem cells (MSCs), and cancer cells. At both the transcriptomic and functional levels, 3D spheroid formation resulted in commitment towards known cell-specific functional outcomes. Surprisingly in all cell types, downregulation of the cholesterol synthesis pathway was found during 3D spheroid formation, with modulation concomitantly affecting 3D spheroid formation and cell-specific consequences; similar results were seen with human cell types. Furthermore, improved antioxidant capacity after 3D spheroid formation across cell types was further enhanced with modulation of the pathway. These findings demonstrate the profound cell-specific consequences and the translational value of understanding conserved mechanisms across diverse cell types after 3D spheroid formation.https://www.mdpi.com/2073-4409/12/16/2050three-dimensional (3D) spheroid formationpluripotent stem cellsmesenchymal stem cellscancer cellscholesterol synthesiscytoskeleton modification |
| spellingShingle | Chia-Chi Chang Shih-Sheng Jiang Fang-Yu Tsai Pei-Ju Hsu Chen-Chan Hsieh Li-Tzu Wang Men-Luh Yen B. Linju Yen Targeting Conserved Pathways in 3D Spheroid Formation of Diverse Cell Types for Translational Application: Enhanced Functional and Antioxidant Capacity Cells three-dimensional (3D) spheroid formation pluripotent stem cells mesenchymal stem cells cancer cells cholesterol synthesis cytoskeleton modification |
| title | Targeting Conserved Pathways in 3D Spheroid Formation of Diverse Cell Types for Translational Application: Enhanced Functional and Antioxidant Capacity |
| title_full | Targeting Conserved Pathways in 3D Spheroid Formation of Diverse Cell Types for Translational Application: Enhanced Functional and Antioxidant Capacity |
| title_fullStr | Targeting Conserved Pathways in 3D Spheroid Formation of Diverse Cell Types for Translational Application: Enhanced Functional and Antioxidant Capacity |
| title_full_unstemmed | Targeting Conserved Pathways in 3D Spheroid Formation of Diverse Cell Types for Translational Application: Enhanced Functional and Antioxidant Capacity |
| title_short | Targeting Conserved Pathways in 3D Spheroid Formation of Diverse Cell Types for Translational Application: Enhanced Functional and Antioxidant Capacity |
| title_sort | targeting conserved pathways in 3d spheroid formation of diverse cell types for translational application enhanced functional and antioxidant capacity |
| topic | three-dimensional (3D) spheroid formation pluripotent stem cells mesenchymal stem cells cancer cells cholesterol synthesis cytoskeleton modification |
| url | https://www.mdpi.com/2073-4409/12/16/2050 |
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