Pub Date : 2025-04-24DOI: 10.1016/j.devcel.2025.04.004
Wanxin Guo, Congcong Zhang, Qianjun Zhou, Tianxiang Chen, Xin Xu, Jianfeng Zhang, Xuewen Yu, Han Wu, Xiao Zhang, Lifang Ma, Kun Qian, Daniel J. Klionsky, Rui Kang, Guido Kroemer, Yongchun Yu, Daolin Tang, Jiayi Wang
Ferroptosis is a type of oxidative cell death, although its key metabolic processes remain incompletely understood. Here, we employ a comprehensive multiomics screening approach that identified cellular communication network factor 1 (CCN1) as a metabolic catalyst of ferroptosis. Upon ferroptosis induction, CCN1 relocates to mitochondrial complexes, facilitating electron transfer flavoprotein subunit alpha (ETFA)-dependent fatty acid β-oxidation. Compared with a traditional carnitine O-palmitoyltransferase 2 (CPT2)-ETFA pathway, the CCN1-ETFA pathway provides additional substrates for mitochondrial reactive oxygen species production, thereby stimulating ferroptosis through lipid peroxidation. A high-fat diet can enhance the anticancer efficacy of ferroptosis in lung cancer mouse models, depending on CCN1. Furthermore, primary lung cancer cells derived from patients with hypertriglyceridemia or high CCN1 expression demonstrate increased susceptibility to ferroptosis in vitro and in vivo. These findings do not only identify the metabolic role of mitochondrial CCN1 but also establish a strategy for enhancing ferroptosis-based anticancer therapies.
{"title":"Mitochondrial CCN1 drives ferroptosis via fatty acid β-oxidation","authors":"Wanxin Guo, Congcong Zhang, Qianjun Zhou, Tianxiang Chen, Xin Xu, Jianfeng Zhang, Xuewen Yu, Han Wu, Xiao Zhang, Lifang Ma, Kun Qian, Daniel J. Klionsky, Rui Kang, Guido Kroemer, Yongchun Yu, Daolin Tang, Jiayi Wang","doi":"10.1016/j.devcel.2025.04.004","DOIUrl":"https://doi.org/10.1016/j.devcel.2025.04.004","url":null,"abstract":"Ferroptosis is a type of oxidative cell death, although its key metabolic processes remain incompletely understood. Here, we employ a comprehensive multiomics screening approach that identified cellular communication network factor 1 (CCN1) as a metabolic catalyst of ferroptosis. Upon ferroptosis induction, CCN1 relocates to mitochondrial complexes, facilitating electron transfer flavoprotein subunit alpha (ETFA)-dependent fatty acid β-oxidation. Compared with a traditional carnitine O-palmitoyltransferase 2 (CPT2)-ETFA pathway, the CCN1-ETFA pathway provides additional substrates for mitochondrial reactive oxygen species production, thereby stimulating ferroptosis through lipid peroxidation. A high-fat diet can enhance the anticancer efficacy of ferroptosis in lung cancer mouse models, depending on CCN1. Furthermore, primary lung cancer cells derived from patients with hypertriglyceridemia or high CCN1 expression demonstrate increased susceptibility to ferroptosis <em>in vitro</em> and <em>in vivo</em>. These findings do not only identify the metabolic role of mitochondrial CCN1 but also establish a strategy for enhancing ferroptosis-based anticancer therapies.","PeriodicalId":11157,"journal":{"name":"Developmental cell","volume":"219 1","pages":""},"PeriodicalIF":11.8,"publicationDate":"2025-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143866994","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 : 2025-04-22DOI: 10.1016/j.devcel.2025.04.002
Kehui Zhu, Jinchao Chen, Long Zhao, Fangfang Lu, Jia Deng, Xuelei Lin, Chongsheng He, Doris Wagner, Jun Xiao
Crucial to plant development, ambient temperature triggers intricate mechanisms enabling adaptive responses to temperature variations. The precise coordination of chromatin modifications in shaping cell developmental fate under diverse temperatures remains elusive. Our study, integrating comprehensive transcriptome, epigenome profiling, and genetics, demonstrates that lower ambient temperature (16°C) partially restores developmental defects caused by H3K27me3 loss in prc2 mutants by specifically depositing H2A.Zub at ectopically expressed embryonic genes in Arabidopsis, such as ABA INSENSITIVE 3 (ABI3) and LEAFY COTYLEDON 1 (LEC1). This deposition leads to downregulation of these genes and compensates for H3K27me3 depletion. Polycomb-repressive complex 1 (PRC1)-catalyzed H2A.Zub and PRC2-catalyzed H3K27me3 play roles in silencing transcription of embryonic genes for post-germination development. Low-temperature-induced reduction of TOE1 protein level decelerates H2A.Z turnover at specific loci, sustaining repression of embryonic genes and alleviating requirement for PRC2-H3K27me3 at post-germination stage. Our findings offer mechanistic insights into the cooperative epigenetic layers, facilitating plant adaptation to varying environmental temperatures.
{"title":"Dynamic control of H2A.Zub and H3K27me3 by ambient temperature during cell fate determination in Arabidopsis","authors":"Kehui Zhu, Jinchao Chen, Long Zhao, Fangfang Lu, Jia Deng, Xuelei Lin, Chongsheng He, Doris Wagner, Jun Xiao","doi":"10.1016/j.devcel.2025.04.002","DOIUrl":"https://doi.org/10.1016/j.devcel.2025.04.002","url":null,"abstract":"Crucial to plant development, ambient temperature triggers intricate mechanisms enabling adaptive responses to temperature variations. The precise coordination of chromatin modifications in shaping cell developmental fate under diverse temperatures remains elusive. Our study, integrating comprehensive transcriptome, epigenome profiling, and genetics, demonstrates that lower ambient temperature (16°C) partially restores developmental defects caused by H3K27me3 loss in <em>prc2</em> mutants by specifically depositing H2A.Zub at ectopically expressed embryonic genes in <em>Arabidopsis</em>, such as <em>ABA INSENSITIVE 3</em> (<em>ABI3</em>) and <em>LEAFY COTYLEDON 1</em> (<em>LEC1</em>). This deposition leads to downregulation of these genes and compensates for H3K27me3 depletion. Polycomb-repressive complex 1 (PRC1)-catalyzed H2A.Zub and PRC2-catalyzed H3K27me3 play roles in silencing transcription of embryonic genes for post-germination development. Low-temperature-induced reduction of TOE1 protein level decelerates H2A.Z turnover at specific loci, sustaining repression of embryonic genes and alleviating requirement for PRC2-H3K27me3 at post-germination stage. Our findings offer mechanistic insights into the cooperative epigenetic layers, facilitating plant adaptation to varying environmental temperatures.","PeriodicalId":11157,"journal":{"name":"Developmental cell","volume":"29 1","pages":""},"PeriodicalIF":11.8,"publicationDate":"2025-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143857780","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 : 2025-04-21DOI: 10.1016/j.devcel.2025.04.001
Danfeng Wang, Hongyan Guo, Xinru Gong, Lichao Chen, Huifang Lin, Shiping Wang, Tianpeng Feng, Yanyan Yi, Wan Wang, Shuhua Yang, Jie Le, Lixin Zhang, Jianru Zuo
In plants, stomata on the aerial epidermis play critical roles in various biological processes, including gas exchange, photosynthesis, transpiration, and immunity. Stomatal development is negatively and positively controlled by the mitogen-activated protein kinase (MAPK) cascade and nitric oxide (NO), respectively. However, the regulatory scheme of stomatal development by these signaling pathways remains elusive. Here, we show that NO-controlled stomatal development in Arabidopsis is genetically dependent on MPK3 and MPK6. Moreover, NO-controlled S-nitrosylation of MPK6 at cysteine (Cys)-201 inhibits its phosphorylation, resulting in the stabilization of SPEECHLESS (SPCH), a master regulator of stomatal lineage initiation, thereby promoting stomatal development. An MPK6C201S mutation confers NO insensitivity during stomatal development and stress responses. We propose that NO positively controls stomatal development and stress responses by inhibiting the MPK6 activity via S-nitrosylation, thus identifying a mechanism linking the coupled NO-MAPK signaling to specific biological outputs.
{"title":"Nitric oxide controls stomatal development and stress responses by inhibiting MPK6 phosphorylation via S-nitrosylation in Arabidopsis","authors":"Danfeng Wang, Hongyan Guo, Xinru Gong, Lichao Chen, Huifang Lin, Shiping Wang, Tianpeng Feng, Yanyan Yi, Wan Wang, Shuhua Yang, Jie Le, Lixin Zhang, Jianru Zuo","doi":"10.1016/j.devcel.2025.04.001","DOIUrl":"https://doi.org/10.1016/j.devcel.2025.04.001","url":null,"abstract":"In plants, stomata on the aerial epidermis play critical roles in various biological processes, including gas exchange, photosynthesis, transpiration, and immunity. Stomatal development is negatively and positively controlled by the mitogen-activated protein kinase (MAPK) cascade and nitric oxide (NO), respectively. However, the regulatory scheme of stomatal development by these signaling pathways remains elusive. Here, we show that NO-controlled stomatal development in <em>Arabidopsis</em> is genetically dependent on <em>MPK3</em> and <em>MPK6</em>. Moreover, NO-controlled <em>S</em>-nitrosylation of MPK6 at cysteine (Cys)-201 inhibits its phosphorylation, resulting in the stabilization of SPEECHLESS (SPCH), a master regulator of stomatal lineage initiation, thereby promoting stomatal development. An <em>MPK6</em><sup><em>C201S</em></sup> mutation confers NO insensitivity during stomatal development and stress responses. We propose that NO positively controls stomatal development and stress responses by inhibiting the MPK6 activity via <em>S</em>-nitrosylation, thus identifying a mechanism linking the coupled NO-MAPK signaling to specific biological outputs.","PeriodicalId":11157,"journal":{"name":"Developmental cell","volume":"56 1","pages":""},"PeriodicalIF":11.8,"publicationDate":"2025-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143853191","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 : 2025-04-21DOI: 10.1016/j.devcel.2025.03.014
Nicholas R. Smith, Nicole R. Giske, Sidharth K. Sengupta, Patrick Conley, John R. Swain, Ashvin Nair, Kathryn L. Fowler, Christopher Klocke, Yeon Jung Yoo, Ashley N. Anderson, Nasim Sanati, Kristof Torkenczy, Andrew C. Adey, Jared M. Fischer, Guanming Wu, Melissa H. Wong
Intestinal epithelial development and homeostasis critically rely upon balanced stem cell proliferation, involving slow-cycling/label-retaining and active-cycling/canonical Wnt-dependent intestinal stem cell (ISC) subtypes. ISC regulation during development remains poorly understood but has important implications for establishing key mechanisms governing tissue maintenance. Herein, we identify Bmi1+ cells as functional stem cells present in early murine intestinal development, prior to Lgr5-expressing ISCs. Lineage tracing and single-cell RNA sequencing identify that Bmi1+ ISCs can trace to Lgr5+ ISCs and other differentiated lineages. Initially highly proliferative, Bmi1+ ISCs transition to slow-cycling states as Lgr5+ ISCs emerge. Non-canonical Wnt signaling regulates the proliferative Bmi1+ cell state. These findings highlight the dynamic interplay between stem cell populations and the opposing Wnt pathways that govern proliferation—ultimately having implications for tissue development, homeostasis, regeneration, and tumorigenesis. Understanding these fundamental developmental mechanisms is critical for understanding adult intestinal maintenance.
{"title":"Dual states of murine Bmi1-expressing intestinal stem cells drive epithelial development utilizing non-canonical Wnt signaling","authors":"Nicholas R. Smith, Nicole R. Giske, Sidharth K. Sengupta, Patrick Conley, John R. Swain, Ashvin Nair, Kathryn L. Fowler, Christopher Klocke, Yeon Jung Yoo, Ashley N. Anderson, Nasim Sanati, Kristof Torkenczy, Andrew C. Adey, Jared M. Fischer, Guanming Wu, Melissa H. Wong","doi":"10.1016/j.devcel.2025.03.014","DOIUrl":"https://doi.org/10.1016/j.devcel.2025.03.014","url":null,"abstract":"Intestinal epithelial development and homeostasis critically rely upon balanced stem cell proliferation, involving slow-cycling/label-retaining and active-cycling/canonical Wnt-dependent intestinal stem cell (ISC) subtypes. ISC regulation during development remains poorly understood but has important implications for establishing key mechanisms governing tissue maintenance. Herein, we identify Bmi1<sup>+</sup> cells as functional stem cells present in early murine intestinal development, prior to Lgr5-expressing ISCs. Lineage tracing and single-cell RNA sequencing identify that Bmi1<sup>+</sup> ISCs can trace to Lgr5<sup>+</sup> ISCs and other differentiated lineages. Initially highly proliferative, Bmi1<sup>+</sup> ISCs transition to slow-cycling states as Lgr5<sup>+</sup> ISCs emerge. Non-canonical Wnt signaling regulates the proliferative Bmi1<sup>+</sup> cell state. These findings highlight the dynamic interplay between stem cell populations and the opposing Wnt pathways that govern proliferation—ultimately having implications for tissue development, homeostasis, regeneration, and tumorigenesis. Understanding these fundamental developmental mechanisms is critical for understanding adult intestinal maintenance.","PeriodicalId":11157,"journal":{"name":"Developmental cell","volume":"10 1","pages":""},"PeriodicalIF":11.8,"publicationDate":"2025-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143853192","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 : 2025-04-21DOI: 10.1016/j.devcel.2025.03.013
Alisdair R. Fernie, Feng Zhu
Metabolic immunity is a powerful mechanism by which plants defend themselves. In a recent issue of Science, Miao et al. identify that erucamide, a primary fatty amide resulting from the condensation of the carboxy group of erucic acid with ammonia present in many plant species, inhibits type III injectisome assembly as an ancient conserved defense mechanism.
{"title":"Chemical disarmament in plant defense: Erucamide blocks bacterial type III injectisome assembly","authors":"Alisdair R. Fernie, Feng Zhu","doi":"10.1016/j.devcel.2025.03.013","DOIUrl":"https://doi.org/10.1016/j.devcel.2025.03.013","url":null,"abstract":"Metabolic immunity is a powerful mechanism by which plants defend themselves. In a recent issue of <em>Science</em>, Miao et al. identify that erucamide, a primary fatty amide resulting from the condensation of the carboxy group of erucic acid with ammonia present in many plant species, inhibits type III injectisome assembly as an ancient conserved defense mechanism.","PeriodicalId":11157,"journal":{"name":"Developmental cell","volume":"268 1","pages":""},"PeriodicalIF":11.8,"publicationDate":"2025-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143853182","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 : 2025-04-21DOI: 10.1016/j.devcel.2025.03.015
Laura L. Thomas, Devavrat M. Bodas, Geraldine Seydoux
In this issue of Developmental Cell, Huang et al. generate a library of C. elegans strains to systematically characterize germ granule composition. This survey catalogs condensate proteins in an intact organism using endogenous tags and sets the stage for future studies of condensate composition and function.
{"title":"Nuage in color: Systematic protein tagging shows the compositional complexity of germ granules","authors":"Laura L. Thomas, Devavrat M. Bodas, Geraldine Seydoux","doi":"10.1016/j.devcel.2025.03.015","DOIUrl":"https://doi.org/10.1016/j.devcel.2025.03.015","url":null,"abstract":"In this issue of <em>Developmental Cell</em>, Huang et al. generate a library of <em>C. elegans</em> strains to systematically characterize germ granule composition. This survey catalogs condensate proteins in an intact organism using endogenous tags and sets the stage for future studies of condensate composition and function.","PeriodicalId":11157,"journal":{"name":"Developmental cell","volume":"4 1","pages":""},"PeriodicalIF":11.8,"publicationDate":"2025-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143853193","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 : 2025-04-21DOI: 10.1016/j.devcel.2025.03.012
Eva Benková
In this issue of Developmental Cell, Lee et al. identify a pivotal role for glutathione (GSH) in plant regeneration, a vital biological process enabling plants to regrow tissues and organs after injury. Applying single-cell RNA sequencing (scRNA-seq) and live imaging, the authors demonstrate that GSH, released upon tissue damage, accelerates cell-cycle transitions, particularly shortening the G1 phase, thereby facilitating efficient organ regeneration.
{"title":"Unlocking plant regeneration: The role for glutathione","authors":"Eva Benková","doi":"10.1016/j.devcel.2025.03.012","DOIUrl":"https://doi.org/10.1016/j.devcel.2025.03.012","url":null,"abstract":"In this issue of <em>Developmental Cell</em>, Lee et al. identify a pivotal role for glutathione (GSH) in plant regeneration, a vital biological process enabling plants to regrow tissues and organs after injury. Applying single-cell RNA sequencing (scRNA-seq) and live imaging, the authors demonstrate that GSH, released upon tissue damage, accelerates cell-cycle transitions, particularly shortening the G1 phase, thereby facilitating efficient organ regeneration.","PeriodicalId":11157,"journal":{"name":"Developmental cell","volume":"82 1","pages":""},"PeriodicalIF":11.8,"publicationDate":"2025-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143853168","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 : 2025-04-21DOI: 10.1016/j.devcel.2025.03.016
Tsunetoshi Nakatani, Tamas Schauer, Mrinmoy Pal, Andreas Ettinger, Luis Altamirano-Pacheco, Julia Zorn, David M. Gilbert, Maria-Elena Torres-Padilla
Cells must duplicate their genome before they divide to ensure equal transmission of genetic information. The genome is replicated with a defined temporal order, replication timing (RT), which is cell-type specific and linked to 3D-genome organization. During mammalian development, RT is initially not well defined and becomes progressively consolidated from the 4-cell stage. However, the molecular regulators are unknown. Here, by combining loss-of-function analysis with genome-wide investigation of RT in mouse embryos, we identify Rap1 interacting factor 1 (RIF1) as a regulator of the progressive consolidation of RT. Embryos without RIF1 show DNA replication features of an early, more totipotent state. RIF1 regulates the progressive stratification of RT values and its depletion leads to global RT changes and a more heterogeneous RT program. Developmental RT changes are disentangled from changes in transcription and nuclear organization, specifically nuclear lamina association. Our work provides molecular understanding of replication and genome organization at the beginning of mammalian development.
{"title":"RIF1 controls replication timing in early mouse embryos independently of lamina-associated nuclear organization","authors":"Tsunetoshi Nakatani, Tamas Schauer, Mrinmoy Pal, Andreas Ettinger, Luis Altamirano-Pacheco, Julia Zorn, David M. Gilbert, Maria-Elena Torres-Padilla","doi":"10.1016/j.devcel.2025.03.016","DOIUrl":"https://doi.org/10.1016/j.devcel.2025.03.016","url":null,"abstract":"Cells must duplicate their genome before they divide to ensure equal transmission of genetic information. The genome is replicated with a defined temporal order, replication timing (RT), which is cell-type specific and linked to 3D-genome organization. During mammalian development, RT is initially not well defined and becomes progressively consolidated from the 4-cell stage. However, the molecular regulators are unknown. Here, by combining loss-of-function analysis with genome-wide investigation of RT in mouse embryos, we identify Rap1 interacting factor 1 (RIF1) as a regulator of the progressive consolidation of RT. Embryos without RIF1 show DNA replication features of an early, more totipotent state. RIF1 regulates the progressive stratification of RT values and its depletion leads to global RT changes and a more heterogeneous RT program. Developmental RT changes are disentangled from changes in transcription and nuclear organization, specifically nuclear lamina association. Our work provides molecular understanding of replication and genome organization at the beginning of mammalian development.","PeriodicalId":11157,"journal":{"name":"Developmental cell","volume":"108 1","pages":""},"PeriodicalIF":11.8,"publicationDate":"2025-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143853190","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 hypothalamus, an “ancient” subcortical brain structure, maintains physiological homeostasis and controls native behaviors. The evolution of homeostatic regulation and behavioral control in mammals may rely on adaptable neuronal identity establishment but conserved neural patterning mechanisms during neurodevelopment. Here, we combined single-cell, single-nucleus, and spatial transcriptomic datasets to map the spatial patterning of diverse progenitor domains and reconstruct their neurogenic lineages in the developing human and mouse hypothalamus. While the regional organizers orchestrating neural patterning are conserved between primates and rodents, we identified a human-enriched neuronal subtype and found a substantial increase in neuromodulatory gene expression among human neurons. Furthermore, cross-species comparison demonstrated a potential redistribution of two neuroendocrine neuronal subtypes and a shift in inter-transmitter and transmitter-peptide coupling within hypothalamic dopamine neurons. Together, our study lays a critical foundation for understanding cellular development and evolution of the mammalian hypothalamus.
{"title":"Transcriptional conservation and evolutionary divergence of cell types across mammalian hypothalamus development","authors":"Zhen-Hua Chen, Taotao Bruce Pan, Yu-Hong Zhang, Ben Wang, Xue-Lian Sun, Meixi Gao, Yang Sun, Mingrui Xu, Shuhui Han, Xiang Shi, Felipe Correa-da-Silva, Chenlu Yang, Junfu Guo, Haoda Wu, Yu Zheng Li, Xiu-Qin Liu, Fei Gao, Zhiheng Xu, Shengjin Xu, Xin Liu, Qing-Feng Wu","doi":"10.1016/j.devcel.2025.03.009","DOIUrl":"https://doi.org/10.1016/j.devcel.2025.03.009","url":null,"abstract":"The hypothalamus, an “ancient” subcortical brain structure, maintains physiological homeostasis and controls native behaviors. The evolution of homeostatic regulation and behavioral control in mammals may rely on adaptable neuronal identity establishment but conserved neural patterning mechanisms during neurodevelopment. Here, we combined single-cell, single-nucleus, and spatial transcriptomic datasets to map the spatial patterning of diverse progenitor domains and reconstruct their neurogenic lineages in the developing human and mouse hypothalamus. While the regional organizers orchestrating neural patterning are conserved between primates and rodents, we identified a human-enriched neuronal subtype and found a substantial increase in neuromodulatory gene expression among human neurons. Furthermore, cross-species comparison demonstrated a potential redistribution of two neuroendocrine neuronal subtypes and a shift in inter-transmitter and transmitter-peptide coupling within hypothalamic dopamine neurons. Together, our study lays a critical foundation for understanding cellular development and evolution of the mammalian hypothalamus.","PeriodicalId":11157,"journal":{"name":"Developmental cell","volume":"92 1","pages":""},"PeriodicalIF":11.8,"publicationDate":"2025-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143798387","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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