Comprehensive Characterization of Bihormonal Cells and Endocrine Cell Lineages in Mammalian Pancreatic Islets
Abstract Understanding the role and prevalence of bihormonal cells in pancreatic islets and their potential in β‐cell restoration is critical but remains ambiguous. Using genetically engineered mouse strains with specific fluorescent markers and advanced imaging flow cytometry, it is found that biho...
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Wiley
2025-08-01
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| Series: | Advanced Science |
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| Online Access: | https://doi.org/10.1002/advs.202416326 |
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| author | Xin‐Xin Yu Peng Peng Yi‐Ning Wang Mao‐Yang He Shuang He Chen‐Tao Jin Liu Yang Xi Wang Jia‐Xi Zheng Jie Gao Cheng‐Ran Xu |
| author_facet | Xin‐Xin Yu Peng Peng Yi‐Ning Wang Mao‐Yang He Shuang He Chen‐Tao Jin Liu Yang Xi Wang Jia‐Xi Zheng Jie Gao Cheng‐Ran Xu |
| author_sort | Xin‐Xin Yu |
| collection | DOAJ |
| description | Abstract Understanding the role and prevalence of bihormonal cells in pancreatic islets and their potential in β‐cell restoration is critical but remains ambiguous. Using genetically engineered mouse strains with specific fluorescent markers and advanced imaging flow cytometry, it is found that bihormonal cells are exceedingly rare. Single‐cell RNA sequencing reveals that Gcg+Ppy+ and Gcg+Ins+ bihormonal cells closely resemble α‐cells or PP‐cells and α‐cells, respectively, indicating they are neither unique lineages nor transitional states. Dual‐recombinase lineage tracing further demonstrates that embryonic Gcg+Ins+ cells resolve into monohormonal α‐cells. Applying these insights, the scarcity of bihormonal cells in diabetic mouse models is confirmed, suggesting a limited role in β‐cell regeneration. By excluding bihormonal influences, endocrine cell classification is redefined in mouse and human islets through gene coexpression network analysis, identifying distinct subtypes and regulatory modules while uncovering species‐specific differences. Additionally, two unique δ‐cell subpopulations are identified in human islets. Collectively, this study provides a comprehensive characterization of bihormonal cells, refines endocrine cell taxonomy, and underscores the translational challenges in modeling human islet biology in mice. |
| format | Article |
| id | doaj-art-24c47f8acd1344ed90db8bbf0f5a2436 |
| institution | Kabale University |
| issn | 2198-3844 |
| language | English |
| publishDate | 2025-08-01 |
| publisher | Wiley |
| record_format | Article |
| series | Advanced Science |
| spelling | doaj-art-24c47f8acd1344ed90db8bbf0f5a24362025-08-20T11:56:10ZengWileyAdvanced Science2198-38442025-08-011230n/an/a10.1002/advs.202416326Comprehensive Characterization of Bihormonal Cells and Endocrine Cell Lineages in Mammalian Pancreatic IsletsXin‐Xin Yu0Peng Peng1Yi‐Ning Wang2Mao‐Yang He3Shuang He4Chen‐Tao Jin5Liu Yang6Xi Wang7Jia‐Xi Zheng8Jie Gao9Cheng‐Ran Xu10State Key Laboratory of Female Fertility Promotion Department of Medical Genetics School of Basic Medical Sciences Peking University Beijing 100191 ChinaState Key Laboratory of Female Fertility Promotion Department of Medical Genetics School of Basic Medical Sciences Peking University Beijing 100191 ChinaState Key Laboratory of Female Fertility Promotion Department of Medical Genetics School of Basic Medical Sciences Peking University Beijing 100191 ChinaState Key Laboratory of Female Fertility Promotion Department of Medical Genetics School of Basic Medical Sciences Peking University Beijing 100191 ChinaPeking‐Tsinghua Center for Life Sciences Peking University Beijing 100871 ChinaState Key Laboratory of Female Fertility Promotion Department of Medical Genetics School of Basic Medical Sciences Peking University Beijing 100191 ChinaState Key Laboratory of Female Fertility Promotion Department of Medical Genetics School of Basic Medical Sciences Peking University Beijing 100191 ChinaState Key Laboratory of Female Fertility Promotion Department of Medical Genetics School of Basic Medical Sciences Peking University Beijing 100191 ChinaDepartment of Hepatobiliary Surgery Peking University People's Hospital Beijing 100044 ChinaDepartment of Hepatobiliary Surgery Peking University People's Hospital Beijing 100044 ChinaState Key Laboratory of Female Fertility Promotion Department of Medical Genetics School of Basic Medical Sciences Peking University Beijing 100191 ChinaAbstract Understanding the role and prevalence of bihormonal cells in pancreatic islets and their potential in β‐cell restoration is critical but remains ambiguous. Using genetically engineered mouse strains with specific fluorescent markers and advanced imaging flow cytometry, it is found that bihormonal cells are exceedingly rare. Single‐cell RNA sequencing reveals that Gcg+Ppy+ and Gcg+Ins+ bihormonal cells closely resemble α‐cells or PP‐cells and α‐cells, respectively, indicating they are neither unique lineages nor transitional states. Dual‐recombinase lineage tracing further demonstrates that embryonic Gcg+Ins+ cells resolve into monohormonal α‐cells. Applying these insights, the scarcity of bihormonal cells in diabetic mouse models is confirmed, suggesting a limited role in β‐cell regeneration. By excluding bihormonal influences, endocrine cell classification is redefined in mouse and human islets through gene coexpression network analysis, identifying distinct subtypes and regulatory modules while uncovering species‐specific differences. Additionally, two unique δ‐cell subpopulations are identified in human islets. Collectively, this study provides a comprehensive characterization of bihormonal cells, refines endocrine cell taxonomy, and underscores the translational challenges in modeling human islet biology in mice.https://doi.org/10.1002/advs.202416326δ‐cell subpopulationsbihormonal cellsendocrine cell heterogeneitygene coexpression networkimaging flow cytometrypancreatic islets |
| spellingShingle | Xin‐Xin Yu Peng Peng Yi‐Ning Wang Mao‐Yang He Shuang He Chen‐Tao Jin Liu Yang Xi Wang Jia‐Xi Zheng Jie Gao Cheng‐Ran Xu Comprehensive Characterization of Bihormonal Cells and Endocrine Cell Lineages in Mammalian Pancreatic Islets Advanced Science δ‐cell subpopulations bihormonal cells endocrine cell heterogeneity gene coexpression network imaging flow cytometry pancreatic islets |
| title | Comprehensive Characterization of Bihormonal Cells and Endocrine Cell Lineages in Mammalian Pancreatic Islets |
| title_full | Comprehensive Characterization of Bihormonal Cells and Endocrine Cell Lineages in Mammalian Pancreatic Islets |
| title_fullStr | Comprehensive Characterization of Bihormonal Cells and Endocrine Cell Lineages in Mammalian Pancreatic Islets |
| title_full_unstemmed | Comprehensive Characterization of Bihormonal Cells and Endocrine Cell Lineages in Mammalian Pancreatic Islets |
| title_short | Comprehensive Characterization of Bihormonal Cells and Endocrine Cell Lineages in Mammalian Pancreatic Islets |
| title_sort | comprehensive characterization of bihormonal cells and endocrine cell lineages in mammalian pancreatic islets |
| topic | δ‐cell subpopulations bihormonal cells endocrine cell heterogeneity gene coexpression network imaging flow cytometry pancreatic islets |
| url | https://doi.org/10.1002/advs.202416326 |
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