Rotating culture regulates the formation of HepaRG-derived liver organoids via YAP translocation
Abstract Background Liver organoid serves as an alternative model for liver pathophysiology in carbohydrate or lipid metabolism and xenobiotic metabolism transformation. Biomechanical cues including spaceflight mission can affect liver organoid construction and their related functions, but their und...
Saved in:
| Main Authors: | , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
BMC
2024-11-01
|
| Series: | BMC Biology |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12915-024-02062-1 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1846164858873053184 |
|---|---|
| author | Shaoyu Zhong Lu Zheng Yi Wu Shujin Sun Qing Luo Guanbin Song Dongyuan Lü Mian Long |
| author_facet | Shaoyu Zhong Lu Zheng Yi Wu Shujin Sun Qing Luo Guanbin Song Dongyuan Lü Mian Long |
| author_sort | Shaoyu Zhong |
| collection | DOAJ |
| description | Abstract Background Liver organoid serves as an alternative model for liver pathophysiology in carbohydrate or lipid metabolism and xenobiotic metabolism transformation. Biomechanical cues including spaceflight mission can affect liver organoid construction and their related functions, but their underlying mechanisms are not fully understood yet. Here, a rotating cell culture device, namely Rotating Flat Chamber (RFC), was specifically designed for adhering cells or cell aggregated to elucidate the effects of altered gravity vector on HepaRG-derived liver organoids construction. Results The organoids so formed under RFC presented the fast growth rate and large projection area. Meanwhile, the expressions of two pluripotency markers of SOX9 and CD44 were enhanced. This finding was positively correlated with the increased YAP expression and nuclear translocation as well as the elevated α4β6-integrin expression. Inhibition of YAP expression and nuclear translocation decreased the expression of SOX9 and CD44 under RFC, thereby attenuating the pluripotency of HepaRG-derived liver organoids. Conclusions In conclusion, we proposed a novel liver organoid construction method using rotating culture, by which the pluripotency of liver organoids so constructed is mediated by α4β6-integrin and YAP translocation. This work furthered the understanding in how the gravity vector orientation affects the construction of liver organoids and the related mechanotransductive pathways. |
| format | Article |
| id | doaj-art-546ebd79c0b34e848b6a116b1e6f01f1 |
| institution | Kabale University |
| issn | 1741-7007 |
| language | English |
| publishDate | 2024-11-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Biology |
| spelling | doaj-art-546ebd79c0b34e848b6a116b1e6f01f12024-11-17T12:48:51ZengBMCBMC Biology1741-70072024-11-0122111510.1186/s12915-024-02062-1Rotating culture regulates the formation of HepaRG-derived liver organoids via YAP translocationShaoyu Zhong0Lu Zheng1Yi Wu2Shujin Sun3Qing Luo4Guanbin Song5Dongyuan Lü6Mian Long7Center for Biomechanics and Bioengineering, Beijing Key Laboratory of Engineered Construction and Mechanobiology and Key Laboratory of Microgravity (National Microgravity Laboratory), Institute of Mechanics, Chinese Academy of SciencesCenter for Biomechanics and Bioengineering, Beijing Key Laboratory of Engineered Construction and Mechanobiology and Key Laboratory of Microgravity (National Microgravity Laboratory), Institute of Mechanics, Chinese Academy of SciencesCenter for Biomechanics and Bioengineering, Beijing Key Laboratory of Engineered Construction and Mechanobiology and Key Laboratory of Microgravity (National Microgravity Laboratory), Institute of Mechanics, Chinese Academy of SciencesCenter for Biomechanics and Bioengineering, Beijing Key Laboratory of Engineered Construction and Mechanobiology and Key Laboratory of Microgravity (National Microgravity Laboratory), Institute of Mechanics, Chinese Academy of SciencesKey Laboratory of Biorheological Science and Technology, Ministry of Education, College of Bioengineering, Chongqing UniversityKey Laboratory of Biorheological Science and Technology, Ministry of Education, College of Bioengineering, Chongqing UniversityCenter for Biomechanics and Bioengineering, Beijing Key Laboratory of Engineered Construction and Mechanobiology and Key Laboratory of Microgravity (National Microgravity Laboratory), Institute of Mechanics, Chinese Academy of SciencesCenter for Biomechanics and Bioengineering, Beijing Key Laboratory of Engineered Construction and Mechanobiology and Key Laboratory of Microgravity (National Microgravity Laboratory), Institute of Mechanics, Chinese Academy of SciencesAbstract Background Liver organoid serves as an alternative model for liver pathophysiology in carbohydrate or lipid metabolism and xenobiotic metabolism transformation. Biomechanical cues including spaceflight mission can affect liver organoid construction and their related functions, but their underlying mechanisms are not fully understood yet. Here, a rotating cell culture device, namely Rotating Flat Chamber (RFC), was specifically designed for adhering cells or cell aggregated to elucidate the effects of altered gravity vector on HepaRG-derived liver organoids construction. Results The organoids so formed under RFC presented the fast growth rate and large projection area. Meanwhile, the expressions of two pluripotency markers of SOX9 and CD44 were enhanced. This finding was positively correlated with the increased YAP expression and nuclear translocation as well as the elevated α4β6-integrin expression. Inhibition of YAP expression and nuclear translocation decreased the expression of SOX9 and CD44 under RFC, thereby attenuating the pluripotency of HepaRG-derived liver organoids. Conclusions In conclusion, we proposed a novel liver organoid construction method using rotating culture, by which the pluripotency of liver organoids so constructed is mediated by α4β6-integrin and YAP translocation. This work furthered the understanding in how the gravity vector orientation affects the construction of liver organoids and the related mechanotransductive pathways.https://doi.org/10.1186/s12915-024-02062-1Liver organoidsHepaRG cellsRotating Flat ChamberRotating cultureYAPMechanotransduction |
| spellingShingle | Shaoyu Zhong Lu Zheng Yi Wu Shujin Sun Qing Luo Guanbin Song Dongyuan Lü Mian Long Rotating culture regulates the formation of HepaRG-derived liver organoids via YAP translocation BMC Biology Liver organoids HepaRG cells Rotating Flat Chamber Rotating culture YAP Mechanotransduction |
| title | Rotating culture regulates the formation of HepaRG-derived liver organoids via YAP translocation |
| title_full | Rotating culture regulates the formation of HepaRG-derived liver organoids via YAP translocation |
| title_fullStr | Rotating culture regulates the formation of HepaRG-derived liver organoids via YAP translocation |
| title_full_unstemmed | Rotating culture regulates the formation of HepaRG-derived liver organoids via YAP translocation |
| title_short | Rotating culture regulates the formation of HepaRG-derived liver organoids via YAP translocation |
| title_sort | rotating culture regulates the formation of heparg derived liver organoids via yap translocation |
| topic | Liver organoids HepaRG cells Rotating Flat Chamber Rotating culture YAP Mechanotransduction |
| url | https://doi.org/10.1186/s12915-024-02062-1 |
| work_keys_str_mv | AT shaoyuzhong rotatingcultureregulatestheformationofhepargderivedliverorganoidsviayaptranslocation AT luzheng rotatingcultureregulatestheformationofhepargderivedliverorganoidsviayaptranslocation AT yiwu rotatingcultureregulatestheformationofhepargderivedliverorganoidsviayaptranslocation AT shujinsun rotatingcultureregulatestheformationofhepargderivedliverorganoidsviayaptranslocation AT qingluo rotatingcultureregulatestheformationofhepargderivedliverorganoidsviayaptranslocation AT guanbinsong rotatingcultureregulatestheformationofhepargderivedliverorganoidsviayaptranslocation AT dongyuanlu rotatingcultureregulatestheformationofhepargderivedliverorganoidsviayaptranslocation AT mianlong rotatingcultureregulatestheformationofhepargderivedliverorganoidsviayaptranslocation |