hESCs‐derived Organoids Achieve Liver Zonation Features through LSEC Modulation
Abstract Liver zonation, essential for diverse physiological functions, is lacking in existing organoid models, hindering their ability to recapitulate liver development and pathogenesis. Addressing this gap, this work explores the feasibility of achieving zonated organoid by co‐culturing human embr...
Saved in:
| Main Authors: | , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Wiley
2025-05-01
|
| Series: | Advanced Science |
| Subjects: | |
| Online Access: | https://doi.org/10.1002/advs.202411667 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1849694196909211648 |
|---|---|
| author | Yuying Zhang Chenyan Huang Lei Sun Lyu Zhou Yudi Niu Kaini Liang Bingjie Wu Peng Zhao Zhiqiang Liu Xiaolin Zhou Peng Zhang Jianchen Wu Jie Na Yanan Du |
| author_facet | Yuying Zhang Chenyan Huang Lei Sun Lyu Zhou Yudi Niu Kaini Liang Bingjie Wu Peng Zhao Zhiqiang Liu Xiaolin Zhou Peng Zhang Jianchen Wu Jie Na Yanan Du |
| author_sort | Yuying Zhang |
| collection | DOAJ |
| description | Abstract Liver zonation, essential for diverse physiological functions, is lacking in existing organoid models, hindering their ability to recapitulate liver development and pathogenesis. Addressing this gap, this work explores the feasibility of achieving zonated organoid by co‐culturing human embryonic stem cells (hESCs) derived hepatocytes (HEP) with hESCs derived liver sinusoidal endothelial cells (LSECs) exhibiting characteristics of either the liver lobule's pericentral (PC) or periportal (PP) regions. Introducing zonated LSECs with variable WNT2 signaling subtly regulate hepatocyte zonation, resulting in noticeable metabolic function changes. Considering the lipid metabolism variations in PC and PP organoids, this work constructs biomimetic zonated metabolic dysfunction‐associated steatotic liver disease (MASLD) organoids and revealed that glucagon‐like peptide‐1 receptor agonist (GLP‐1RA) directly target LSECs, indicating potential therapeutic mechanisms of GLP‐1RA in MAFLD alleviation. This study highlights the crucial role of non‐parenchymal cells in organoids for recapitulating niche heterogeneity, offering further insights for drug discovery and in vitro modeling of organ heterogeneity. |
| format | Article |
| id | doaj-art-422b6d3abcd94e64a5b71bbfd63d2510 |
| institution | DOAJ |
| issn | 2198-3844 |
| language | English |
| publishDate | 2025-05-01 |
| publisher | Wiley |
| record_format | Article |
| series | Advanced Science |
| spelling | doaj-art-422b6d3abcd94e64a5b71bbfd63d25102025-08-20T03:20:10ZengWileyAdvanced Science2198-38442025-05-011220n/an/a10.1002/advs.202411667hESCs‐derived Organoids Achieve Liver Zonation Features through LSEC ModulationYuying Zhang0Chenyan Huang1Lei Sun2Lyu Zhou3Yudi Niu4Kaini Liang5Bingjie Wu6Peng Zhao7Zhiqiang Liu8Xiaolin Zhou9Peng Zhang10Jianchen Wu11Jie Na12Yanan Du13School of Biomedical Engineering, Tsinghua‐Peking Center for Life Sciences Tsinghua University Beijing 100084 ChinaDepartment of Molecular Biology Princeton University Princeton NJ 08544 USASchool of Biomedical Engineering, Tsinghua‐Peking Center for Life Sciences Tsinghua University Beijing 100084 ChinaSchool of Biomedical Engineering, Tsinghua‐Peking Center for Life Sciences Tsinghua University Beijing 100084 ChinaSchool of Biomedical Engineering, Tsinghua‐Peking Center for Life Sciences Tsinghua University Beijing 100084 ChinaSchool of Biomedical Engineering, Tsinghua‐Peking Center for Life Sciences Tsinghua University Beijing 100084 ChinaSchool of Biomedical Engineering, Tsinghua‐Peking Center for Life Sciences Tsinghua University Beijing 100084 ChinaSchool of Biomedical Engineering, Tsinghua‐Peking Center for Life Sciences Tsinghua University Beijing 100084 ChinaSchool of Biomedical Engineering, Tsinghua‐Peking Center for Life Sciences Tsinghua University Beijing 100084 ChinaInstitution of Medical Science University of Toronto Toronto Ontario M5S1A8 CanadaBeijing Key Laboratory for Genetics of Birth Defects, Beijing Pediatric Research Institute, MOE Key Laboratory of Major Diseases in Children; Rare Disease Center, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health Beijing 100045 ChinaSchool of Basic Medical Science, Tsinghua Medicine Tsinghua University Beijing 100084 ChinaSchool of Basic Medical Science, Tsinghua Medicine Tsinghua University Beijing 100084 ChinaSchool of Biomedical Engineering, Tsinghua‐Peking Center for Life Sciences Tsinghua University Beijing 100084 ChinaAbstract Liver zonation, essential for diverse physiological functions, is lacking in existing organoid models, hindering their ability to recapitulate liver development and pathogenesis. Addressing this gap, this work explores the feasibility of achieving zonated organoid by co‐culturing human embryonic stem cells (hESCs) derived hepatocytes (HEP) with hESCs derived liver sinusoidal endothelial cells (LSECs) exhibiting characteristics of either the liver lobule's pericentral (PC) or periportal (PP) regions. Introducing zonated LSECs with variable WNT2 signaling subtly regulate hepatocyte zonation, resulting in noticeable metabolic function changes. Considering the lipid metabolism variations in PC and PP organoids, this work constructs biomimetic zonated metabolic dysfunction‐associated steatotic liver disease (MASLD) organoids and revealed that glucagon‐like peptide‐1 receptor agonist (GLP‐1RA) directly target LSECs, indicating potential therapeutic mechanisms of GLP‐1RA in MAFLD alleviation. This study highlights the crucial role of non‐parenchymal cells in organoids for recapitulating niche heterogeneity, offering further insights for drug discovery and in vitro modeling of organ heterogeneity.https://doi.org/10.1002/advs.202411667GLP‐1RhESCs‐derived LSECliver zonationMAFLDPEGMA‐grafted PDMS microwell chipzonated organoids |
| spellingShingle | Yuying Zhang Chenyan Huang Lei Sun Lyu Zhou Yudi Niu Kaini Liang Bingjie Wu Peng Zhao Zhiqiang Liu Xiaolin Zhou Peng Zhang Jianchen Wu Jie Na Yanan Du hESCs‐derived Organoids Achieve Liver Zonation Features through LSEC Modulation Advanced Science GLP‐1R hESCs‐derived LSEC liver zonation MAFLD PEGMA‐grafted PDMS microwell chip zonated organoids |
| title | hESCs‐derived Organoids Achieve Liver Zonation Features through LSEC Modulation |
| title_full | hESCs‐derived Organoids Achieve Liver Zonation Features through LSEC Modulation |
| title_fullStr | hESCs‐derived Organoids Achieve Liver Zonation Features through LSEC Modulation |
| title_full_unstemmed | hESCs‐derived Organoids Achieve Liver Zonation Features through LSEC Modulation |
| title_short | hESCs‐derived Organoids Achieve Liver Zonation Features through LSEC Modulation |
| title_sort | hescs derived organoids achieve liver zonation features through lsec modulation |
| topic | GLP‐1R hESCs‐derived LSEC liver zonation MAFLD PEGMA‐grafted PDMS microwell chip zonated organoids |
| url | https://doi.org/10.1002/advs.202411667 |
| work_keys_str_mv | AT yuyingzhang hescsderivedorganoidsachieveliverzonationfeaturesthroughlsecmodulation AT chenyanhuang hescsderivedorganoidsachieveliverzonationfeaturesthroughlsecmodulation AT leisun hescsderivedorganoidsachieveliverzonationfeaturesthroughlsecmodulation AT lyuzhou hescsderivedorganoidsachieveliverzonationfeaturesthroughlsecmodulation AT yudiniu hescsderivedorganoidsachieveliverzonationfeaturesthroughlsecmodulation AT kainiliang hescsderivedorganoidsachieveliverzonationfeaturesthroughlsecmodulation AT bingjiewu hescsderivedorganoidsachieveliverzonationfeaturesthroughlsecmodulation AT pengzhao hescsderivedorganoidsachieveliverzonationfeaturesthroughlsecmodulation AT zhiqiangliu hescsderivedorganoidsachieveliverzonationfeaturesthroughlsecmodulation AT xiaolinzhou hescsderivedorganoidsachieveliverzonationfeaturesthroughlsecmodulation AT pengzhang hescsderivedorganoidsachieveliverzonationfeaturesthroughlsecmodulation AT jianchenwu hescsderivedorganoidsachieveliverzonationfeaturesthroughlsecmodulation AT jiena hescsderivedorganoidsachieveliverzonationfeaturesthroughlsecmodulation AT yanandu hescsderivedorganoidsachieveliverzonationfeaturesthroughlsecmodulation |