Pub Date : 2025-01-09DOI: 10.1016/j.devcel.2024.12.027
Anna Solé-Gil, Yuuki Sakai, Bruno Catarino, Victor A.S. Jones, Christopher E. Youngstrom, Joan Jordà-Segura, Chi-Lien Cheng, Liam Dolan, Barbara A. Ambrose, Kimitsune Ishizaki, Miguel A. Blázquez, Javier Agustí
Plants adapted to life on land by developing diverse anatomical features across lineages. The molecular basis of these innovations often involves the emergence of new genes or establishing new connections between conserved elements, though evidence for evolutionary genetic circuit rewiring remains scarce. Here, we show that the thermospermine-dependent pathway regulating vascular cell proliferation in Arabidopsis thaliana operates as two distinct modules with different functions in the bryophyte Marchantia polymorpha. One module controls dichotomous branching at meristems, while the other one modulates gemmae and rhizoid production in the thallus. Heterologous assays and comparative expression analyses reveal that the molecular links between these modules, forming a unified circuit in vascular plants, emerged early in tracheophyte evolution. Our results illustrate how the thermospermine-dependent circuit elements followed two divergent evolutionary trajectories in bryophytes and tracheophytes, eventually influencing distinct developmental processes.
{"title":"Divergent evolution of a thermospermine-dependent regulatory pathway in land plants","authors":"Anna Solé-Gil, Yuuki Sakai, Bruno Catarino, Victor A.S. Jones, Christopher E. Youngstrom, Joan Jordà-Segura, Chi-Lien Cheng, Liam Dolan, Barbara A. Ambrose, Kimitsune Ishizaki, Miguel A. Blázquez, Javier Agustí","doi":"10.1016/j.devcel.2024.12.027","DOIUrl":"https://doi.org/10.1016/j.devcel.2024.12.027","url":null,"abstract":"Plants adapted to life on land by developing diverse anatomical features across lineages. The molecular basis of these innovations often involves the emergence of new genes or establishing new connections between conserved elements, though evidence for evolutionary genetic circuit rewiring remains scarce. Here, we show that the thermospermine-dependent pathway regulating vascular cell proliferation in <em>Arabidopsis thaliana</em> operates as two distinct modules with different functions in the bryophyte <em>Marchantia polymorpha</em>. One module controls dichotomous branching at meristems, while the other one modulates gemmae and rhizoid production in the thallus. Heterologous assays and comparative expression analyses reveal that the molecular links between these modules, forming a unified circuit in vascular plants, emerged early in tracheophyte evolution. Our results illustrate how the thermospermine-dependent circuit elements followed two divergent evolutionary trajectories in bryophytes and tracheophytes, eventually influencing distinct developmental processes.","PeriodicalId":11157,"journal":{"name":"Developmental cell","volume":"470 1","pages":""},"PeriodicalIF":11.8,"publicationDate":"2025-01-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142937019","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
During pollen-stigma interaction, pollen coat protein B-class peptides (PCP-Bs) compete with stigmatic rapid alkalinization factor (RALF) for interaction with FERONIA/ANJEA receptor kinases (FER/ANJ), stimulating pollen hydration and germination. However, the molecular mechanism underlying PCP-Bs-induced, FER/ANJ-regulated compatible responses remains largely unknown. Through PCP-Bγ-induced phosphoproteomic analysis, we characterized a series of pollination-related signaling pathways regulated by FER/ANJ. Interestingly, on stigmatic papillary cells, pollen PCP-Bγ induced an elevation in cytosolic pH near the plasma membrane (PM), sustained by stigmatic RALF23/33 through regulation of the autoinhibited H+-ATPase 1/2 (AHA1/2) activity. We further found that RALFs/PCP-Bs and FER/ANJ regulated the pH alterations via phosphorylation of AHA1/2 C terminus. Furthermore, RALF23/33–FER/ANJ maintained the protonation of H197 in plasma membrane intrinsic proteins (PIPs), whereas PCP-B relieved the protonation through AHA activity. Altogether, this study reveals that pollen PCP-Bs trigger FER/ANJ-controlled compatible responses, particularly the opening of aquaporins via AHA-mediated pH changes, thereby facilitating pollen hydration in Arabidopsis.
{"title":"PCP-B peptides and CrRLK1L receptor kinases control pollination via pH gating of aquaporins in Arabidopsis","authors":"Zhiwen Liu, Xiaonan Chu, Weiwei Ren, Lijun Cheng, Chen Liu, Congcong Wang, Sihan Gao, Shaojun Dai, Chao Li","doi":"10.1016/j.devcel.2024.12.026","DOIUrl":"https://doi.org/10.1016/j.devcel.2024.12.026","url":null,"abstract":"During pollen-stigma interaction, pollen coat protein B-class peptides (PCP-Bs) compete with stigmatic rapid alkalinization factor (RALF) for interaction with FERONIA/ANJEA receptor kinases (FER/ANJ), stimulating pollen hydration and germination. However, the molecular mechanism underlying PCP-Bs-induced, FER/ANJ-regulated compatible responses remains largely unknown. Through PCP-Bγ-induced phosphoproteomic analysis, we characterized a series of pollination-related signaling pathways regulated by FER/ANJ. Interestingly, on stigmatic papillary cells, pollen PCP-Bγ induced an elevation in cytosolic pH near the plasma membrane (PM), sustained by stigmatic RALF23/33 through regulation of the autoinhibited H<sup>+</sup>-ATPase 1/2 (AHA1/2) activity. We further found that RALFs/PCP-Bs and FER/ANJ regulated the pH alterations via phosphorylation of AHA1/2 C terminus. Furthermore, RALF23/33–FER/ANJ maintained the protonation of H197 in plasma membrane intrinsic proteins (PIPs), whereas PCP-B relieved the protonation through AHA activity. Altogether, this study reveals that pollen PCP-Bs trigger FER/ANJ-controlled compatible responses, particularly the opening of aquaporins via AHA-mediated pH changes, thereby facilitating pollen hydration in <em>Arabidopsis</em>.","PeriodicalId":11157,"journal":{"name":"Developmental cell","volume":"15 1","pages":""},"PeriodicalIF":11.8,"publicationDate":"2025-01-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142937030","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Recent advancements in pluripotent stem cell and synthetic tissue technology have brought significant breakthroughs in studying early embryonic development, particularly within the first trimester of development in humans. However, during fetal stage development, investigating further biological events represents a major challenge, partly due to the evolving complexity and continued interaction across multiple organ systems. To bridge this gap, we propose an “in toto” biological framework that leverages a triad of technologies: synthetic tissues, intravital microscopy, and computer vision to capture in vivo cellular morphodynamics, conceptualized as single-cell choreography. This perspective will discuss the inherent challenges in capturing such complexities and explore engineering technologies to delve into the less-explored phase of human development. We also propose reframing the organ-centric to a system-centric paradigm, as such a framework broadens the value of the in vivo-embedded synthetic-tissue-based approach for interrogating the multifaceted interplay of human developmental processes during this crucial stage.
{"title":"In toto biological framework: Modeling interconnectedness during human development","authors":"Yosuke Yoneyama, Yunheng Wu, Kensaku Mori, Takanori Takebe","doi":"10.1016/j.devcel.2024.09.027","DOIUrl":"https://doi.org/10.1016/j.devcel.2024.09.027","url":null,"abstract":"Recent advancements in pluripotent stem cell and synthetic tissue technology have brought significant breakthroughs in studying early embryonic development, particularly within the first trimester of development in humans. However, during fetal stage development, investigating further biological events represents a major challenge, partly due to the evolving complexity and continued interaction across multiple organ systems. To bridge this gap, we propose an “<em>in toto</em>” biological framework that leverages a triad of technologies: synthetic tissues, intravital microscopy, and computer vision to capture <em>in vivo</em> cellular morphodynamics, conceptualized as single-cell choreography. This perspective will discuss the inherent challenges in capturing such complexities and explore engineering technologies to delve into the less-explored phase of human development. We also propose reframing the organ-centric to a system-centric paradigm, as such a framework broadens the value of the <em>in vivo</em>-embedded synthetic-tissue-based approach for interrogating the multifaceted interplay of human developmental processes during this crucial stage.","PeriodicalId":11157,"journal":{"name":"Developmental cell","volume":"27 1","pages":""},"PeriodicalIF":11.8,"publicationDate":"2025-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142929709","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-01-06DOI: 10.1016/j.devcel.2024.12.008
Marcus Ruscetti
Understanding the impact of senescence on disease is limited by the lack of tools to lineage label senescent cells. In a recent Cell issue, Zhao et al. create mouse models to genetically manipulate and trace p16+ cells, identifying contrasting roles for senescent macrophages and endothelial cells (ECs) in liver fibrosis.
{"title":"Lineage tracing senescence in vivo shows not all senescent cells are created equal","authors":"Marcus Ruscetti","doi":"10.1016/j.devcel.2024.12.008","DOIUrl":"https://doi.org/10.1016/j.devcel.2024.12.008","url":null,"abstract":"Understanding the impact of senescence on disease is limited by the lack of tools to lineage label senescent cells. In a recent <em>Cell</em> issue, Zhao et al. create mouse models to genetically manipulate and trace p16<sup>+</sup> cells, identifying contrasting roles for senescent macrophages and endothelial cells (ECs) in liver fibrosis.","PeriodicalId":11157,"journal":{"name":"Developmental cell","volume":"34 1","pages":""},"PeriodicalIF":11.8,"publicationDate":"2025-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142929389","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-01-06DOI: 10.1016/j.devcel.2024.12.006
Marianne Montemurro, Bruno Monier, Magali Suzanne
Tumors evolve through the acquisition of increasingly aggressive traits associated with dysplasia. This progression is accompanied by alterations in tumor mechanical properties, especially through extracellular matrix remodeling. However, the contribution of pre-tumoral tissue mechanics to tumor aggressiveness remains poorly known in vivo. Here, we show that adherens junction tension in pre-tumoral tissues dictates subsequent tumor evolution in Drosophila. Increased cell contractility, observed in aggressive tumors before any sign of tissue overgrowth, proved sufficient to trigger dysplasia in normally hyperplastic tumors. In addition, high contractility precedes any changes in cell polarity and contributes to tumor evolution through cell death induction, which favors cell-cell junction weakening. Overall, our results highlight the need to re-evaluate the roles of tumoral cell death and identify pre-tumoral cell mechanics as an unsuspected early marker and key trigger of tumor aggressiveness.
{"title":"The mechanical state of pre-tumoral epithelia controls subsequent Drosophila tumor aggressiveness","authors":"Marianne Montemurro, Bruno Monier, Magali Suzanne","doi":"10.1016/j.devcel.2024.12.006","DOIUrl":"https://doi.org/10.1016/j.devcel.2024.12.006","url":null,"abstract":"Tumors evolve through the acquisition of increasingly aggressive traits associated with dysplasia. This progression is accompanied by alterations in tumor mechanical properties, especially through extracellular matrix remodeling. However, the contribution of pre-tumoral tissue mechanics to tumor aggressiveness remains poorly known <em>in vivo</em>. Here, we show that adherens junction tension in pre-tumoral tissues dictates subsequent tumor evolution in <em>Drosophila</em>. Increased cell contractility, observed in aggressive tumors before any sign of tissue overgrowth, proved sufficient to trigger dysplasia in normally hyperplastic tumors. In addition, high contractility precedes any changes in cell polarity and contributes to tumor evolution through cell death induction, which favors cell-cell junction weakening. Overall, our results highlight the need to re-evaluate the roles of tumoral cell death and identify pre-tumoral cell mechanics as an unsuspected early marker and key trigger of tumor aggressiveness.","PeriodicalId":11157,"journal":{"name":"Developmental cell","volume":"21 1","pages":""},"PeriodicalIF":11.8,"publicationDate":"2025-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142929708","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-01-06DOI: 10.1016/j.devcel.2024.12.024
Sofia Brito, Hyojin Heo, Jinyoung Kim, Byungsun Cha, Youngdo Jeong, Wooseon Choi, Chandani Shrestha, Gang Hyoung Lee, Sun Ju Park, Ki Bok Yoon, Kentaro Oh-Hashi, Sung Tae Kim, Sehyun Chae, Sung Kweon Cho, Byung Mook Weon, Jiyoon Kim, Bum-Ho Bin
Golgi abnormalities have been linked to aging and age-related diseases, yet the underlying causes and functional consequences remain poorly understood. This study identifies the interaction between age-associated zinc deficiency and Golgi stress as a critical factor in cellular aging. Senescent Golgi bodies from human fibroblasts show a fragmented Golgi structure, associated with a decreased interaction of the zinc-dependent Golgi-stacking protein complex Golgin45-GRASP55. Golgi stress is increased, and functions such as glycosylation and vesicle transport are impaired. These disturbances promote Golgi and perinuclear microtubule disassembly and subsequent mislocalization of intracellular proteins associated with cellular signaling and epigenetic control. Pharmacological induction of Golgi stress or zinc deficiency, or ablation of the Golgi-associated zinc transporter gene Zip13 in mouse fibroblasts, replicate the characteristics of cellular senescence, emphasizing the critical role of Golgi-zinc homeostasis. These findings highlight the importance of adequate zinc intake and suggest targeting Golgi dysfunction as a therapeutic strategy for alleviating age-related cellular decline.
{"title":"Age-associated interplay between zinc deficiency and Golgi stress hinders microtubule-dependent cellular signaling and epigenetic control","authors":"Sofia Brito, Hyojin Heo, Jinyoung Kim, Byungsun Cha, Youngdo Jeong, Wooseon Choi, Chandani Shrestha, Gang Hyoung Lee, Sun Ju Park, Ki Bok Yoon, Kentaro Oh-Hashi, Sung Tae Kim, Sehyun Chae, Sung Kweon Cho, Byung Mook Weon, Jiyoon Kim, Bum-Ho Bin","doi":"10.1016/j.devcel.2024.12.024","DOIUrl":"https://doi.org/10.1016/j.devcel.2024.12.024","url":null,"abstract":"Golgi abnormalities have been linked to aging and age-related diseases, yet the underlying causes and functional consequences remain poorly understood. This study identifies the interaction between age-associated zinc deficiency and Golgi stress as a critical factor in cellular aging. Senescent Golgi bodies from human fibroblasts show a fragmented Golgi structure, associated with a decreased interaction of the zinc-dependent Golgi-stacking protein complex Golgin45-GRASP55. Golgi stress is increased, and functions such as glycosylation and vesicle transport are impaired. These disturbances promote Golgi and perinuclear microtubule disassembly and subsequent mislocalization of intracellular proteins associated with cellular signaling and epigenetic control. Pharmacological induction of Golgi stress or zinc deficiency, or ablation of the Golgi-associated zinc transporter gene <em>Zip13</em> in mouse fibroblasts, replicate the characteristics of cellular senescence, emphasizing the critical role of Golgi-zinc homeostasis. These findings highlight the importance of adequate zinc intake and suggest targeting Golgi dysfunction as a therapeutic strategy for alleviating age-related cellular decline.","PeriodicalId":11157,"journal":{"name":"Developmental cell","volume":"19 1","pages":""},"PeriodicalIF":11.8,"publicationDate":"2025-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142929388","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-01-06DOI: 10.1016/j.devcel.2024.12.029
Kawthar F. Alashoor, Salim Al-Babili
The phytohormone strigolactone (SL) regulates various developmental processes and plant adaptation to nutrient availability, which in turn regulates strigolactone biosynthesis. In the recent issue of Cell, Hu et al.1 advance the understanding of the interaction of the SL receptor complex and reveal exciting insights into the nitrogen-dependent regulation of SL signaling and SL-dependent tillering in rice.
{"title":"How structural interactions and receptor phosphorylation shape strigolactone signaling in rice","authors":"Kawthar F. Alashoor, Salim Al-Babili","doi":"10.1016/j.devcel.2024.12.029","DOIUrl":"https://doi.org/10.1016/j.devcel.2024.12.029","url":null,"abstract":"The phytohormone strigolactone (SL) regulates various developmental processes and plant adaptation to nutrient availability, which in turn regulates strigolactone biosynthesis. In the recent issue of <em>Cell</em>, Hu et al.<span><span><sup>1</sup></span></span> advance the understanding of the interaction of the SL receptor complex and reveal exciting insights into the nitrogen-dependent regulation of SL signaling and SL-dependent tillering in rice.","PeriodicalId":11157,"journal":{"name":"Developmental cell","volume":"100 1","pages":""},"PeriodicalIF":11.8,"publicationDate":"2025-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142929711","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-01-06DOI: 10.1016/j.devcel.2024.12.017
Robert G. Kelly
Addition of epithelial progenitor cells drives progressive extension of the heart tube during cardiac morphogenesis. In this issue of Developmental Cell, Arriagada et al. (2024) refine our understanding of how these cells condition and interact with the underlying extracellular matrix, demonstrating that autonomous fibronectin synthesis controls their apicobasal polarity and deployment to the heart.
{"title":"Matrix interactions regulate epithelial polarity and cohesion in the second heart field","authors":"Robert G. Kelly","doi":"10.1016/j.devcel.2024.12.017","DOIUrl":"https://doi.org/10.1016/j.devcel.2024.12.017","url":null,"abstract":"Addition of epithelial progenitor cells drives progressive extension of the heart tube during cardiac morphogenesis. In this issue of <em>Developmental Cell,</em> Arriagada et al. (2024) refine our understanding of how these cells condition and interact with the underlying extracellular matrix, demonstrating that autonomous fibronectin synthesis controls their apicobasal polarity and deployment to the heart.","PeriodicalId":11157,"journal":{"name":"Developmental cell","volume":"34 1","pages":""},"PeriodicalIF":11.8,"publicationDate":"2025-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142929725","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-01-06DOI: 10.1016/j.devcel.2024.12.021
Zhimin Li, Ziqi Liang, Huan Qi, Xing Luo, Min Wang, Zhuo Du, Weixiang Guo
Lactate has emerged as a central metabolic fuel and an important signaling molecule. Its availability participates in various brain functions. Although lactate homeostasis is vital for adult hippocampal neurogenesis and cognition, it is still unknown how shuttles lactate across the plasma membrane of neural stem cells (NSCs) to control their activity and neurogenic potential. In this study, we show that monocarboxylate transporter (MCT)1 and MCT2, respectively, control efflux and influx of lactate in the murine NSCs, thereby maintaining intracellular lactate homeostasis. Mechanistically, lactate shuttling links histone lactylation to govern NSC proliferation through MDM2-p53 signaling pathway. Notably, genetic ablation of MCT2 from NSCs or pharmacological inhibition of MDM2-P53 interaction prevents voluntary running-induced NSC proliferation in the murine adult hippocampus. Taken together, our findings demonstrate that lactate shuttling controls histone lactylation, which acts as a nexus for controlling adult hippocampal neurogenesis.
{"title":"Lactate shuttling links histone lactylation to adult hippocampal neurogenesis in mice","authors":"Zhimin Li, Ziqi Liang, Huan Qi, Xing Luo, Min Wang, Zhuo Du, Weixiang Guo","doi":"10.1016/j.devcel.2024.12.021","DOIUrl":"https://doi.org/10.1016/j.devcel.2024.12.021","url":null,"abstract":"Lactate has emerged as a central metabolic fuel and an important signaling molecule. Its availability participates in various brain functions. Although lactate homeostasis is vital for adult hippocampal neurogenesis and cognition, it is still unknown how shuttles lactate across the plasma membrane of neural stem cells (NSCs) to control their activity and neurogenic potential. In this study, we show that monocarboxylate transporter (MCT)1 and MCT2, respectively, control efflux and influx of lactate in the murine NSCs, thereby maintaining intracellular lactate homeostasis. Mechanistically, lactate shuttling links histone lactylation to govern NSC proliferation through MDM2-p53 signaling pathway. Notably, genetic ablation of MCT2 from NSCs or pharmacological inhibition of MDM2-P53 interaction prevents voluntary running-induced NSC proliferation in the murine adult hippocampus. Taken together, our findings demonstrate that lactate shuttling controls histone lactylation, which acts as a nexus for controlling adult hippocampal neurogenesis.","PeriodicalId":11157,"journal":{"name":"Developmental cell","volume":"42 1","pages":""},"PeriodicalIF":11.8,"publicationDate":"2025-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142929424","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
The intestinal microbiota is a key environmental factor in the development of colorectal cancer (CRC). Here, we report that, in the context of mild colonic inflammation, the microbiota protects against colorectal tumorigenesis in mice. This protection is achieved by microbial suppression of the long non-coding RNA (lncRNA) Snhg9. Snhg9 promotes tumor growth through inhibition of the tumor suppressor p53. Snhg9 suppresses p53 activity by dissociating the p53 deacetylase sirtuin 1 (SIRT1) from the cell cycle and apoptosis regulator 2 (CCAR2). Consequently, the depletion of the microbiota by antibiotics causes upregulation of Snhg9 and accelerates CRC progression. Moreover, Snhg9 is functionally conserved. Human SNHG9 promotes tumor growth via the same mechanism as mouse Snhg9, despite their low sequence similarity.
{"title":"Gut microbiota protect against colorectal tumorigenesis through lncRNA Snhg9","authors":"Meng Wang, Kailin Liu, Wu Bao, Bingqing Hang, Xianjiong Chen, Xinyi Zhu, Guifang Li, Lihong Liu, Haoyi Xiang, Hai Hu, Yanhui Lu, Zhangfa Song, Jiaxin Chen, Yuhao Wang","doi":"10.1016/j.devcel.2024.12.013","DOIUrl":"https://doi.org/10.1016/j.devcel.2024.12.013","url":null,"abstract":"The intestinal microbiota is a key environmental factor in the development of colorectal cancer (CRC). Here, we report that, in the context of mild colonic inflammation, the microbiota protects against colorectal tumorigenesis in mice. This protection is achieved by microbial suppression of the long non-coding RNA (lncRNA) <em>Snhg9</em>. <em>Snhg9</em> promotes tumor growth through inhibition of the tumor suppressor p53. <em>Snhg9</em> suppresses p53 activity by dissociating the p53 deacetylase sirtuin 1 (SIRT1) from the cell cycle and apoptosis regulator 2 (CCAR2). Consequently, the depletion of the microbiota by antibiotics causes upregulation of <em>Snhg9</em> and accelerates CRC progression. Moreover, <em>Snhg9</em> is functionally conserved. Human <em>SNHG9</em> promotes tumor growth via the same mechanism as mouse <em>Snhg9</em>, despite their low sequence similarity.","PeriodicalId":11157,"journal":{"name":"Developmental cell","volume":"155 1","pages":""},"PeriodicalIF":11.8,"publicationDate":"2025-01-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142917748","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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