Cold-induced FOXO1 nuclear transport aids cold survival and tissue storage
Abstract Cold-induced injuries severely limit opportunities and outcomes of hypothermic therapies and organ preservation, calling for better understanding of cold adaptation. Here, by surveying cold-altered chromatin accessibility and integrated CUT&Tag/RNA-seq analyses in human stem cells, we r...
| Main Authors: | , , , , , , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Nature Portfolio
2024-04-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-024-47095-w |
| _version_ | 1797219764333969408 |
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| author | Xiaomei Zhang Lihao Ge Guanghui Jin Yasong Liu Qingfen Yu Weizhao Chen Liang Chen Tao Dong Kiyoharu J. Miyagishima Juan Shen Jinghong Yang Guo Lv Yan Xu Qing Yang Linsen Ye Shuhong Yi Hua Li Qi Zhang Guihua Chen Wei Liu Yang Yang Wei Li Jingxing Ou |
| author_facet | Xiaomei Zhang Lihao Ge Guanghui Jin Yasong Liu Qingfen Yu Weizhao Chen Liang Chen Tao Dong Kiyoharu J. Miyagishima Juan Shen Jinghong Yang Guo Lv Yan Xu Qing Yang Linsen Ye Shuhong Yi Hua Li Qi Zhang Guihua Chen Wei Liu Yang Yang Wei Li Jingxing Ou |
| author_sort | Xiaomei Zhang |
| collection | DOAJ |
| description | Abstract Cold-induced injuries severely limit opportunities and outcomes of hypothermic therapies and organ preservation, calling for better understanding of cold adaptation. Here, by surveying cold-altered chromatin accessibility and integrated CUT&Tag/RNA-seq analyses in human stem cells, we reveal forkhead box O1 (FOXO1) as a key transcription factor for autonomous cold adaptation. Accordingly, we find a nonconventional, temperature-sensitive FOXO1 transport mechanism involving the nuclear pore complex protein RANBP2, SUMO-modification of transporter proteins Importin-7 and Exportin-1, and a SUMO-interacting motif on FOXO1. Our conclusions are supported by cold survival experiments with human cell models and zebrafish larvae. Promoting FOXO1 nuclear entry by the Exportin-1 inhibitor KPT-330 enhances cold tolerance in pre-diabetic obese mice, and greatly prolongs the shelf-life of human and mouse pancreatic tissues and islets. Transplantation of mouse islets cold-stored for 14 days reestablishes normoglycemia in diabetic mice. Our findings uncover a regulatory network and potential therapeutic targets to boost spontaneous cold adaptation. |
| first_indexed | 2024-04-24T12:38:50Z |
| format | Article |
| id | doaj.art-d998e4517370496592792e959647a452 |
| institution | Directory Open Access Journal |
| issn | 2041-1723 |
| language | English |
| last_indexed | 2024-04-24T12:38:50Z |
| publishDate | 2024-04-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj.art-d998e4517370496592792e959647a4522024-04-07T11:23:57ZengNature PortfolioNature Communications2041-17232024-04-0115111710.1038/s41467-024-47095-wCold-induced FOXO1 nuclear transport aids cold survival and tissue storageXiaomei Zhang0Lihao Ge1Guanghui Jin2Yasong Liu3Qingfen Yu4Weizhao Chen5Liang Chen6Tao Dong7Kiyoharu J. Miyagishima8Juan Shen9Jinghong Yang10Guo Lv11Yan Xu12Qing Yang13Linsen Ye14Shuhong Yi15Hua Li16Qi Zhang17Guihua Chen18Wei Liu19Yang Yang20Wei Li21Jingxing Ou22Department of Hepatic Surgery and Liver transplantation Center of the Third Affiliated Hospital, Organ Transplantation Institute, Sun Yat-sen UniversityInstitute of Psychiatry and Neuroscience, Xinxiang Medical UniversityDepartment of Hepatic Surgery and Liver transplantation Center of the Third Affiliated Hospital, Organ Transplantation Institute, Sun Yat-sen UniversityDepartment of Hepatic Surgery and Liver transplantation Center of the Third Affiliated Hospital, Organ Transplantation Institute, Sun Yat-sen UniversityDepartment of Neurology, The Third Affiliated Hospital of Sun Yat-sen UniversityDepartment of Hepatic Surgery and Liver transplantation Center of the Third Affiliated Hospital, Organ Transplantation Institute, Sun Yat-sen UniversityDepartment of Hepatic Surgery and Liver transplantation Center of the Third Affiliated Hospital, Organ Transplantation Institute, Sun Yat-sen UniversityDepartment of Hepatic Surgery and Liver transplantation Center of the Third Affiliated Hospital, Organ Transplantation Institute, Sun Yat-sen UniversityRetinal Neurophysiology Section, National Eye Institute, National Institutes of HealthGuangdong Key Laboratory of Liver Disease Research, the Third Affiliated Hospital of Sun Yat-sen UniversityDepartment of Hepatic Surgery and Liver transplantation Center of the Third Affiliated Hospital, Organ Transplantation Institute, Sun Yat-sen UniversityGuangdong province engineering laboratory for transplantation medicineCell-gene Therapy Translational Medicine Research Center, the Third Affiliated Hospital of Sun Yat-sen UniversityDepartment of Hepatic Surgery and Liver transplantation Center of the Third Affiliated Hospital, Organ Transplantation Institute, Sun Yat-sen UniversityDepartment of Hepatic Surgery and Liver transplantation Center of the Third Affiliated Hospital, Organ Transplantation Institute, Sun Yat-sen UniversityDepartment of Hepatic Surgery and Liver transplantation Center of the Third Affiliated Hospital, Organ Transplantation Institute, Sun Yat-sen UniversityDepartment of Hepatic Surgery and Liver transplantation Center of the Third Affiliated Hospital, Organ Transplantation Institute, Sun Yat-sen UniversityGuangdong Key Laboratory of Liver Disease Research, the Third Affiliated Hospital of Sun Yat-sen UniversityDepartment of Hepatic Surgery and Liver transplantation Center of the Third Affiliated Hospital, Organ Transplantation Institute, Sun Yat-sen UniversityGuangdong Key Laboratory of Liver Disease Research, the Third Affiliated Hospital of Sun Yat-sen UniversityDepartment of Hepatic Surgery and Liver transplantation Center of the Third Affiliated Hospital, Organ Transplantation Institute, Sun Yat-sen UniversityRetinal Neurophysiology Section, National Eye Institute, National Institutes of HealthDepartment of Hepatic Surgery and Liver transplantation Center of the Third Affiliated Hospital, Organ Transplantation Institute, Sun Yat-sen UniversityAbstract Cold-induced injuries severely limit opportunities and outcomes of hypothermic therapies and organ preservation, calling for better understanding of cold adaptation. Here, by surveying cold-altered chromatin accessibility and integrated CUT&Tag/RNA-seq analyses in human stem cells, we reveal forkhead box O1 (FOXO1) as a key transcription factor for autonomous cold adaptation. Accordingly, we find a nonconventional, temperature-sensitive FOXO1 transport mechanism involving the nuclear pore complex protein RANBP2, SUMO-modification of transporter proteins Importin-7 and Exportin-1, and a SUMO-interacting motif on FOXO1. Our conclusions are supported by cold survival experiments with human cell models and zebrafish larvae. Promoting FOXO1 nuclear entry by the Exportin-1 inhibitor KPT-330 enhances cold tolerance in pre-diabetic obese mice, and greatly prolongs the shelf-life of human and mouse pancreatic tissues and islets. Transplantation of mouse islets cold-stored for 14 days reestablishes normoglycemia in diabetic mice. Our findings uncover a regulatory network and potential therapeutic targets to boost spontaneous cold adaptation.https://doi.org/10.1038/s41467-024-47095-w |
| spellingShingle | Xiaomei Zhang Lihao Ge Guanghui Jin Yasong Liu Qingfen Yu Weizhao Chen Liang Chen Tao Dong Kiyoharu J. Miyagishima Juan Shen Jinghong Yang Guo Lv Yan Xu Qing Yang Linsen Ye Shuhong Yi Hua Li Qi Zhang Guihua Chen Wei Liu Yang Yang Wei Li Jingxing Ou Cold-induced FOXO1 nuclear transport aids cold survival and tissue storage Nature Communications |
| title | Cold-induced FOXO1 nuclear transport aids cold survival and tissue storage |
| title_full | Cold-induced FOXO1 nuclear transport aids cold survival and tissue storage |
| title_fullStr | Cold-induced FOXO1 nuclear transport aids cold survival and tissue storage |
| title_full_unstemmed | Cold-induced FOXO1 nuclear transport aids cold survival and tissue storage |
| title_short | Cold-induced FOXO1 nuclear transport aids cold survival and tissue storage |
| title_sort | cold induced foxo1 nuclear transport aids cold survival and tissue storage |
| url | https://doi.org/10.1038/s41467-024-47095-w |
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