首页 > 最新文献

Developmental cell最新文献

英文 中文
Common mechanisms regulate stem cell self-organization and symmetry breaking across various glandular epithelia 共同机制调节干细胞自组织和对称打破在各种腺上皮
IF 11.8 1区 生物学 Q1 CELL BIOLOGY Pub Date : 2025-10-06 DOI: 10.1016/j.devcel.2025.07.009
Brigida Novello, Cédric Blanpain
In this issue of Developmental Cell, Journot et al. identify a conserved mechanism promoting the development and lineage segregation of multipotent stem cells across different glandular epithelia. p63, YAP, and Notch control symmetry breaking, cell positioning, and cell-fate decision during development and regeneration, illustrating how spatial cues orchestrate tissue self-organization.
在本期的《发育细胞》中,Journot等人发现了一种保守的机制,可以促进多能干细胞在不同腺上皮中的发育和谱系分离。p63, YAP和Notch控制发育和再生过程中的对称性破坏,细胞定位和细胞命运决定,说明空间线索如何协调组织自组织。
{"title":"Common mechanisms regulate stem cell self-organization and symmetry breaking across various glandular epithelia","authors":"Brigida Novello, Cédric Blanpain","doi":"10.1016/j.devcel.2025.07.009","DOIUrl":"https://doi.org/10.1016/j.devcel.2025.07.009","url":null,"abstract":"In this issue of <em>Developmental Cell</em>, Journot et al. identify a conserved mechanism promoting the development and lineage segregation of multipotent stem cells across different glandular epithelia. p63, YAP, and Notch control symmetry breaking, cell positioning, and cell-fate decision during development and regeneration, illustrating how spatial cues orchestrate tissue self-organization.","PeriodicalId":11157,"journal":{"name":"Developmental cell","volume":"82 1","pages":""},"PeriodicalIF":11.8,"publicationDate":"2025-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145229360","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}
引用次数: 0
How glioblastoma stem cells turn inflammatory cues into tumor growth and immune suppression 胶质母细胞瘤干细胞如何将炎症信号转化为肿瘤生长和免疫抑制
IF 11.8 1区 生物学 Q1 CELL BIOLOGY Pub Date : 2025-10-06 DOI: 10.1016/j.devcel.2025.06.011
Wenhui Chen, Yanjie Shen, Guangshuai Jia
Chronic inflammation shapes the tumor microenvironment and influences cancer stem cell behavior. In this issue of Developmental Cell, Gu et al. identify TNFAIP6 as a key responder to tumor necrosis factor alpha (TNF-α) that promotes self-renewal of glioblastoma stem cells and reprograms pro-inflammatory macrophages toward an immunosuppressive phenotype, identifying a therapeutic vulnerability in glioblastoma.
慢性炎症塑造肿瘤微环境并影响癌症干细胞行为。在这一期的Developmental Cell中,Gu等人发现TNFAIP6是肿瘤坏死因子α (TNF-α)的关键应答者,它促进胶质母细胞瘤干细胞的自我更新,并将促炎巨噬细胞重编程为免疫抑制表型,从而确定了胶质母细胞瘤的治疗脆弱性。
{"title":"How glioblastoma stem cells turn inflammatory cues into tumor growth and immune suppression","authors":"Wenhui Chen, Yanjie Shen, Guangshuai Jia","doi":"10.1016/j.devcel.2025.06.011","DOIUrl":"https://doi.org/10.1016/j.devcel.2025.06.011","url":null,"abstract":"Chronic inflammation shapes the tumor microenvironment and influences cancer stem cell behavior. In this issue of <em>Developmental Cell</em>, Gu et al. identify TNFAIP6 as a key responder to tumor necrosis factor alpha (TNF-α) that promotes self-renewal of glioblastoma stem cells and reprograms pro-inflammatory macrophages toward an immunosuppressive phenotype, identifying a therapeutic vulnerability in glioblastoma.","PeriodicalId":11157,"journal":{"name":"Developmental cell","volume":"52 4 1","pages":""},"PeriodicalIF":11.8,"publicationDate":"2025-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145229361","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}
引用次数: 0
Kickstart the cell cycle with a sugar boost: mTOR brake on APC/C-CDH1 triggers a glycolytic pulse 通过糖的增加来启动细胞周期:APC/C-CDH1上的mTOR刹车触发糖酵解脉冲
IF 11.8 1区 生物学 Q1 CELL BIOLOGY Pub Date : 2025-10-06 DOI: 10.1016/j.devcel.2025.09.006
Fangxia Wang, Yuu Kimata
Cells exiting quiescence must simultaneously prepare for DNA replication and boost metabolism. Paul et al.1 now show that mitogen-activated mTOR transiently suppresses APC/C-CDH1, unleashing the glycolytic activator PFKFB3 to provide an energetic pulse that jump-starts proliferation before APC/C is reactivated.
细胞必须同时为DNA复制和促进新陈代谢做准备。Paul等人1现在表明,有丝分裂原激活的mTOR会短暂抑制APC/C- cdh1,释放糖酵解激活剂PFKFB3,在APC/C被重新激活之前提供一个能量脉冲,从而启动增殖。
{"title":"Kickstart the cell cycle with a sugar boost: mTOR brake on APC/C-CDH1 triggers a glycolytic pulse","authors":"Fangxia Wang, Yuu Kimata","doi":"10.1016/j.devcel.2025.09.006","DOIUrl":"https://doi.org/10.1016/j.devcel.2025.09.006","url":null,"abstract":"Cells exiting quiescence must simultaneously prepare for DNA replication and boost metabolism. Paul et al.<span><span><sup>1</sup></span></span> now show that mitogen-activated mTOR transiently suppresses APC/C-CDH1, unleashing the glycolytic activator PFKFB3 to provide an energetic pulse that jump-starts proliferation before APC/C is reactivated.","PeriodicalId":11157,"journal":{"name":"Developmental cell","volume":"75 1","pages":""},"PeriodicalIF":11.8,"publicationDate":"2025-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145229364","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}
引用次数: 0
TMK-PIN1 drives a short self-organizing circuit for auxin export and signaling in Arabidopsis TMK-PIN1驱动拟南芥中生长素输出和信号传导的短自组织电路
IF 11.8 1区 生物学 Q1 CELL BIOLOGY Pub Date : 2025-10-02 DOI: 10.1016/j.devcel.2025.09.009
Rongfeng Huang, Jiacheng Wang, Mingzeng Chang, Wenxin Tang, Yongqiang Yu, Yi Zhang, Yao Peng, Yanan Wang, Yihan Guo, Ting Lu, Yang Cao, Yewei Zhou, Qinglin Zhang, Yuehong Huang, Angxiao Wu, Luyan Ren, Michelle Gallei, Juan Dong, Haodong Chen, Jun He, Tongda Xu
The versatile and pivotal roles of the phytohormone auxin in regulating plant growth and development are typically linked to its directional transport, relying on the polarized PIN-FORMED (PIN) auxin exporters at the plasma membrane (PM). For decades, auxin has been proposed to promote PIN polarization, generating self-regulatory feedback mediating much of plant development, but mechanistic insight into this regulation is lacking. Here, we uncover an auxin-induced protein complex at the PM, containing auxin co-receptors transmembrane kinases (TMKs) and PIN1 auxin exporter, as the core machinery that underlies this feedback regulation. Auxin promotes PIN1 phosphorylation by TMKs, modulating PIN1 polarization and transport activity. We also provide evidence that PIN1-exported extracellular auxin is crucial for TMK activation and cell elongation, thus forming the simplest two-element self-regulatory feedback circuit. Thus, these findings offer direct mechanistic insights into a potential self-organizing circuit for auxin signaling and transport to ensure proper plant development in Arabidopsis.
植物激素生长素在调节植物生长发育中的关键作用通常与其定向运输有关,这种定向运输依赖于质膜(PM)上的极化PIN- formed (PIN)生长素出口蛋白。几十年来,生长素被认为促进PIN极化,产生自我调节反馈,介导了植物的大部分发育,但缺乏对这种调节的机制认识。在这里,我们在PM发现了生长素诱导的蛋白复合物,包含生长素共受体跨膜激酶(TMKs)和生长素输出PIN1,作为这种反馈调节的核心机制。生长素通过TMKs促进PIN1磷酸化,调节PIN1的极化和运输活性。我们还提供证据表明,pin1输出的细胞外生长素对TMK激活和细胞伸长至关重要,从而形成最简单的二元自我调节反馈回路。因此,这些发现为研究生长素信号和运输的潜在自组织回路提供了直接的机制见解,以确保拟南芥植物的正常发育。
{"title":"TMK-PIN1 drives a short self-organizing circuit for auxin export and signaling in Arabidopsis","authors":"Rongfeng Huang, Jiacheng Wang, Mingzeng Chang, Wenxin Tang, Yongqiang Yu, Yi Zhang, Yao Peng, Yanan Wang, Yihan Guo, Ting Lu, Yang Cao, Yewei Zhou, Qinglin Zhang, Yuehong Huang, Angxiao Wu, Luyan Ren, Michelle Gallei, Juan Dong, Haodong Chen, Jun He, Tongda Xu","doi":"10.1016/j.devcel.2025.09.009","DOIUrl":"https://doi.org/10.1016/j.devcel.2025.09.009","url":null,"abstract":"The versatile and pivotal roles of the phytohormone auxin in regulating plant growth and development are typically linked to its directional transport, relying on the polarized PIN-FORMED (PIN) auxin exporters at the plasma membrane (PM). For decades, auxin has been proposed to promote PIN polarization, generating self-regulatory feedback mediating much of plant development, but mechanistic insight into this regulation is lacking. Here, we uncover an auxin-induced protein complex at the PM, containing auxin co-receptors transmembrane kinases (TMKs) and PIN1 auxin exporter, as the core machinery that underlies this feedback regulation. Auxin promotes PIN1 phosphorylation by TMKs, modulating PIN1 polarization and transport activity. We also provide evidence that PIN1-exported extracellular auxin is crucial for TMK activation and cell elongation, thus forming the simplest two-element self-regulatory feedback circuit. Thus, these findings offer direct mechanistic insights into a potential self-organizing circuit for auxin signaling and transport to ensure proper plant development in <em>Arabidopsis</em>.","PeriodicalId":11157,"journal":{"name":"Developmental cell","volume":"214 1","pages":""},"PeriodicalIF":11.8,"publicationDate":"2025-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145204003","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}
引用次数: 0
Epidermal hydrodynamics controls water homeostasis of shoot meristems for plant adaptation to terrestrial environments 表皮水动力学控制着植物芽分生组织的水分稳态,以适应陆地环境
IF 11.8 1区 生物学 Q1 CELL BIOLOGY Pub Date : 2025-09-30 DOI: 10.1016/j.devcel.2025.09.007
Yimin Zhu, Xianmiao Zhu, Simin Bi, Dan Teng, Muhammad Tahir, Yangxuan Liu, Long Wang, Huanhuan Liu, Tingting Wen, Leyao Zhu, Zhenquan Li, Xing Chen, Minhua Zhang, Wenjuan Cai, Zhijun Liu, Mingyue Zheng, Yu Zhang, Ji-Ming Gong, Jia-Wei Wang, Zuhua He, Weibing Yang
Water uptake and redistribution represent a significant challenge for plant colonization of land. While vascular plants have evolved specialized structures for water transport, how water homeostasis is maintained in meristematic tissues remains elusive. Here, we show that the Arabidopsis shoot meristem develops within a high-humidity niche. The homeodomain leucine zipper (HD-ZIP) transcription factor ARABIDOPSIS THALIANA MERISTEM LAYER 1 (ATML1) and its regulatory target PIP2;5 establish a water conduit across L1 cells to facilitate hydraulic exchange with the surrounding microenvironment. The ATML1-PIP2;5 module regulates stem cell activity in response to humidity fluctuations and is associated with local adaptation to arid climates in natural populations. Transcriptional activation of water flux by class IV homeodomain-leucine zipper (C4HDZ) proteins predates the emergence of vascular systems, contributing to hydraulic response in the liverwort Marchantia polymorpha. Our results reveal an evolutionarily conserved epidermal hydraulic pathway that integrates developmental patterning with environmental sensing, highlighting a fundamental role for the shoot meristem in shaping plant adaptation in terrestrial habitats.
水分的吸收和再分配是植物在陆地上定植的一个重大挑战。虽然维管植物已经进化出专门的水运输结构,但如何在分生组织中维持水的稳态仍然是一个谜。在这里,我们表明拟南芥茎分生组织在高湿生态位中发育。同源结构域亮氨酸拉链(HD-ZIP)转录因子拟南芥分生系统层1 (ATML1)及其调控靶点PIP25 .在L1细胞间建立水管,促进与周围微环境的水力交换。ATML1-PIP2;5模块调节干细胞活动以应对湿度波动,并与自然种群对干旱气候的局部适应有关。IV类同源结构域亮氨酸拉链(C4HDZ)蛋白对水通量的转录激活早于血管系统的出现,有助于多形地草的水力反应。我们的研究结果揭示了一个进化上保守的表皮水力通路,它将发育模式与环境感知结合在一起,突出了茎分生组织在塑造植物适应陆地栖息地的基本作用。
{"title":"Epidermal hydrodynamics controls water homeostasis of shoot meristems for plant adaptation to terrestrial environments","authors":"Yimin Zhu, Xianmiao Zhu, Simin Bi, Dan Teng, Muhammad Tahir, Yangxuan Liu, Long Wang, Huanhuan Liu, Tingting Wen, Leyao Zhu, Zhenquan Li, Xing Chen, Minhua Zhang, Wenjuan Cai, Zhijun Liu, Mingyue Zheng, Yu Zhang, Ji-Ming Gong, Jia-Wei Wang, Zuhua He, Weibing Yang","doi":"10.1016/j.devcel.2025.09.007","DOIUrl":"https://doi.org/10.1016/j.devcel.2025.09.007","url":null,"abstract":"Water uptake and redistribution represent a significant challenge for plant colonization of land. While vascular plants have evolved specialized structures for water transport, how water homeostasis is maintained in meristematic tissues remains elusive. Here, we show that the <em>Arabidopsis</em> shoot meristem develops within a high-humidity niche. The homeodomain leucine zipper (HD-ZIP) transcription factor ARABIDOPSIS THALIANA MERISTEM LAYER 1 (ATML1) and its regulatory target <em>PIP2;5</em> establish a water conduit across L1 cells to facilitate hydraulic exchange with the surrounding microenvironment. The ATML1-PIP2;5 module regulates stem cell activity in response to humidity fluctuations and is associated with local adaptation to arid climates in natural populations. Transcriptional activation of water flux by class IV homeodomain-leucine zipper (C4HDZ) proteins predates the emergence of vascular systems, contributing to hydraulic response in the liverwort <em>Marchantia polymorpha</em>. Our results reveal an evolutionarily conserved epidermal hydraulic pathway that integrates developmental patterning with environmental sensing, highlighting a fundamental role for the shoot meristem in shaping plant adaptation in terrestrial habitats.","PeriodicalId":11157,"journal":{"name":"Developmental cell","volume":"11 1","pages":""},"PeriodicalIF":11.8,"publicationDate":"2025-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145189272","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}
引用次数: 0
Human pluripotent stem cell-derived fetal hepatic stellate cells promote vascularization and maturation in liver organoids 人多能干细胞衍生的胎儿肝星状细胞促进肝类器官的血管化和成熟
IF 11.8 1区 生物学 Q1 CELL BIOLOGY Pub Date : 2025-09-29 DOI: 10.1016/j.devcel.2025.09.002
Xia Yang, Yun-Zhong Nie, Chun Lu, Yang Li, Yoshihito Hayashi, Riana Plummer, Na Luo, Qinglin Li, Toshiharu Kasai, Takashi Okumura, Yumiko Isobe, Kiyoshi Yamaguchi, Yoichi Furukawa, Yan Li, Hideki Taniguchi
Human-induced pluripotent stem cell (hiPSC)-derived liver organoids (LOs) are valuable for studying human liver organogenesis but face challenges in faithfully recapitulating certain processes, like vasculogenesis, due to the lack of specific cell components. Hepatic stellate cells (HSCs), which are liver-specific pericytes and might be crucial for liver vasculogenesis, remain underutilized in developmental studies because of their disease-related status and inefficient generation process. Here, we present an efficient method for generating hiPSC-derived HSCs (hiPSC-HSCs) resembling the transcriptomic profiles of fetal human HSCs. These hiPSC-HSCs exhibit exceptional expandability (>105-fold) while maintaining essential cellular features. Additionally, in entirely hiPSC-derived LOs consisting of HSCs, hepatic endoderm, and endothelial cells, hiPSC-HSCs play a vital role in LO maturation and vascularization, both in vitro and in vivo. This work represents a significant advancement in understanding HSC roles in human liver development, and LOs containing hiPSC-HSCs hold potential in modeling congenital human liver diseases.
人类诱导多能干细胞(hiPSC)衍生的肝类器官(LOs)对于研究人类肝脏器官发生具有重要价值,但由于缺乏特定的细胞成分,在忠实再现某些过程(如血管发生)方面面临挑战。肝星状细胞(HSCs)是肝脏特异性周细胞,可能对肝脏血管形成至关重要,但由于其疾病相关状态和低效的生成过程,在发育研究中仍未得到充分利用。在这里,我们提出了一种高效的方法来生成hipsc衍生的造血干细胞(hipsc - hsc),类似于胎儿人造血干细胞的转录组谱。这些hipsc - hsc在保持基本细胞特征的同时表现出卓越的可扩展性(105倍)。此外,在由造血干细胞、肝内胚层和内皮细胞组成的完全由hipsc衍生的LO中,hipsc - hsc在LO成熟和血管化中起着至关重要的作用,无论是在体外还是在体内。这项工作在理解HSC在人类肝脏发育中的作用方面取得了重大进展,并且含有hipsc -HSC的LOs在模拟先天性人类肝脏疾病方面具有潜力。
{"title":"Human pluripotent stem cell-derived fetal hepatic stellate cells promote vascularization and maturation in liver organoids","authors":"Xia Yang, Yun-Zhong Nie, Chun Lu, Yang Li, Yoshihito Hayashi, Riana Plummer, Na Luo, Qinglin Li, Toshiharu Kasai, Takashi Okumura, Yumiko Isobe, Kiyoshi Yamaguchi, Yoichi Furukawa, Yan Li, Hideki Taniguchi","doi":"10.1016/j.devcel.2025.09.002","DOIUrl":"https://doi.org/10.1016/j.devcel.2025.09.002","url":null,"abstract":"Human-induced pluripotent stem cell (hiPSC)-derived liver organoids (LOs) are valuable for studying human liver organogenesis but face challenges in faithfully recapitulating certain processes, like vasculogenesis, due to the lack of specific cell components. Hepatic stellate cells (HSCs), which are liver-specific pericytes and might be crucial for liver vasculogenesis, remain underutilized in developmental studies because of their disease-related status and inefficient generation process. Here, we present an efficient method for generating hiPSC-derived HSCs (hiPSC-HSCs) resembling the transcriptomic profiles of fetal human HSCs. These hiPSC-HSCs exhibit exceptional expandability (&gt;10<sup>5</sup>-fold) while maintaining essential cellular features. Additionally, in entirely hiPSC-derived LOs consisting of HSCs, hepatic endoderm, and endothelial cells, hiPSC-HSCs play a vital role in LO maturation and vascularization, both <em>in vitro</em> and <em>in vivo</em>. This work represents a significant advancement in understanding HSC roles in human liver development, and LOs containing hiPSC-HSCs hold potential in modeling congenital human liver diseases.","PeriodicalId":11157,"journal":{"name":"Developmental cell","volume":"4 1","pages":""},"PeriodicalIF":11.8,"publicationDate":"2025-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145183020","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}
引用次数: 0
Non-cell-autonomous tumor promotion in DICER1 cancer predisposition 非细胞自主肿瘤促进DICER1癌症易感性
IF 11.8 1区 生物学 Q1 CELL BIOLOGY Pub Date : 2025-09-29 DOI: 10.1016/j.devcel.2025.09.001
Randolph K. Larsen, Jason A. Hanna, Hongjian Jin, Kristin B. Reed, Darden W. Kimbrough, Kyna Vuong, Jongchan Hwang, Grace E. Adkins, Jack D. Hopkins, Bradley T. Stevens, Myron K. Evans, Casey G. Langdon, Catherine J. Drummond, Matthew R. Garcia, Kristin B. Wiggins, Amy R. Iverson, David Finkelstein, Patrick A. Schreiner, Jason W. Rosch, Jerold E. Rehg, Mark E. Hatley
DICER1-related tumors are characterized by germline loss-of-function mutations in one DICER1 allele (DICER1+/−) and a somatic “second hit” mutation in the remaining DICER1 allele. Whether the germline DICER1+/− mutation participates in tumorigenesis is unknown. We show that germline heterozygous loss of Dicer1 promotes tumor formation via aberrant neutrophil function in spontaneous and allograft mouse models of rhabdomyosarcoma. Germline heterozygous deletion of Dicer1 decreased tumor latency and increased tumor penetrance, while conditional heterozygous deletion in tumor cells did not, illustrating that non-cell-autonomous contributions were required for tumor promotion. We show that Dicer1+/− murine and human tumors were enriched for neutrophils and that tumor-bearing mice had abundant circulating neutrophil extracellular traps (NETs). Genetically and pharmacologically preventing NET release reduced tumor promotion in Dicer1+/− mice, suggesting NETs promote tumor growth. These findings demonstrate that germline DICER1+/− mutations promote tumor growth and suggest that targeting neutrophils/NET release may reduce cancer risk in DICER1+/− individuals.
DICER1相关肿瘤的特征是一个DICER1等位基因(DICER1+/−)的种系功能丧失突变和其余DICER1等位基因的体细胞“二次打击”突变。种系DICER1+/−突变是否参与肿瘤发生尚不清楚。我们发现,在自发性和同种异体移植小鼠横纹肌肉瘤模型中,种系杂合缺失Dicer1通过异常中性粒细胞功能促进肿瘤形成。种系杂合缺失Dicer1会降低肿瘤潜伏期,增加肿瘤外显率,而肿瘤细胞中的条件杂合缺失则不会,说明肿瘤促进需要非细胞自主贡献。我们发现Dicer1+/−小鼠和人类肿瘤富含中性粒细胞,荷瘤小鼠具有丰富的循环中性粒细胞胞外陷阱(NETs)。从遗传学和药理学上阻止NET的释放可减少Dicer1+/−小鼠的肿瘤促进,表明NET促进肿瘤生长。这些发现表明生殖系DICER1+/ -突变促进肿瘤生长,并提示靶向中性粒细胞/NET释放可能降低DICER1+/ -个体的癌症风险。
{"title":"Non-cell-autonomous tumor promotion in DICER1 cancer predisposition","authors":"Randolph K. Larsen, Jason A. Hanna, Hongjian Jin, Kristin B. Reed, Darden W. Kimbrough, Kyna Vuong, Jongchan Hwang, Grace E. Adkins, Jack D. Hopkins, Bradley T. Stevens, Myron K. Evans, Casey G. Langdon, Catherine J. Drummond, Matthew R. Garcia, Kristin B. Wiggins, Amy R. Iverson, David Finkelstein, Patrick A. Schreiner, Jason W. Rosch, Jerold E. Rehg, Mark E. Hatley","doi":"10.1016/j.devcel.2025.09.001","DOIUrl":"https://doi.org/10.1016/j.devcel.2025.09.001","url":null,"abstract":"DICER1-related tumors are characterized by germline loss-of-function mutations in one <em>DICER1</em> allele (<em>DICER1</em><sup><em>+/−</em></sup>) and a somatic “second hit” mutation in the remaining <em>DICER1</em> allele. Whether the germline <em>DICER1</em><sup><em>+/−</em></sup> mutation participates in tumorigenesis is unknown. We show that germline heterozygous loss of <em>Dicer1</em> promotes tumor formation via aberrant neutrophil function in spontaneous and allograft mouse models of rhabdomyosarcoma. Germline heterozygous deletion of <em>Dicer1</em> decreased tumor latency and increased tumor penetrance, while conditional heterozygous deletion in tumor cells did not, illustrating that non-cell-autonomous contributions were required for tumor promotion. We show that <em>Dicer1</em><sup><em>+/−</em></sup> murine and human tumors were enriched for neutrophils and that tumor-bearing mice had abundant circulating neutrophil extracellular traps (NETs). Genetically and pharmacologically preventing NET release reduced tumor promotion in <em>Dicer1</em><sup><em>+/−</em></sup> mice, suggesting NETs promote tumor growth. These findings demonstrate that germline <em>DICER1</em><sup><em>+/−</em></sup> mutations promote tumor growth and suggest that targeting neutrophils/NET release may reduce cancer risk in <em>DICER1</em><sup><em>+/−</em></sup> individuals.","PeriodicalId":11157,"journal":{"name":"Developmental cell","volume":"118 1","pages":""},"PeriodicalIF":11.8,"publicationDate":"2025-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145183195","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}
引用次数: 0
Lmo3-expressing peri-isthmus progenitor cells sustain renewal and repair of the mammalian intestinal telocyte niche 表达lmo3的峡周祖细胞维持哺乳动物肠远端细胞生态位的更新和修复
IF 11.8 1区 生物学 Q1 CELL BIOLOGY Pub Date : 2025-09-26 DOI: 10.1016/j.devcel.2025.09.004
Daxin Jiang, Guoli Zhu, Yongchao Zhang, Jiawen Wang, Nannan Qian, Zhen Jin, Qingyu Sun, Haimeng Yu, Kebei Tang, Tao Cai, Fengchao Wang, Rongwen Xi
Intestinal telocytes that reside immediately beneath the intestinal epithelium exert niche-supporting roles for intestinal stem cells and their progenies. They are heterogeneous cells compartmentalized along the crypt-villus axis, but the mechanisms governing the maintenance of this telocyte population remain unclear. Here, we identify a distinct population of subepithelial mesenchymal cells in the developing mouse embryo, marked by LIM Domain Only 3 (Lmo3), as the cellular origin of post-natal intestinal telocytes. The Lmo3+ cells emerge prior to villus formation at embryonic day 13.5, and after birth, they progressively acquire a spatial confinement to the intestinal isthmus region, where they persist as long-lived, slow-cycling cells, supplying both peri-villus and peri-crypt telocytes. Further, we show that Lmo3+ cells respond rapidly to tissue damage, becoming activated to promote repair of the telocyte niche. Therefore, a quiescent and damage-responsive progenitor cell population marked by Lmo3 maintains the intestinal telocyte niche.
位于肠上皮下的肠远端细胞对肠干细胞及其后代发挥着生态位支持作用。它们是沿隐窝绒毛轴划分的异质细胞,但控制这种远端细胞群维持的机制尚不清楚。在这里,我们在发育中的小鼠胚胎中发现了一个独特的上皮下间充质细胞群体,以LIM结构域仅3 (Lmo3)为标志,作为出生后肠远端细胞的细胞起源。Lmo3+细胞在胚胎第13.5天绒毛形成之前就出现了,出生后,它们逐渐获得了肠峡区的空间限制,在那里它们作为长寿命、慢循环的细胞持续存在,供应绒毛周围和隐窝周围的远端细胞。此外,我们发现Lmo3+细胞对组织损伤反应迅速,被激活以促进远端细胞生态位的修复。因此,由Lmo3标记的静止和损伤应答的祖细胞群维持了肠远端细胞的生态位。
{"title":"Lmo3-expressing peri-isthmus progenitor cells sustain renewal and repair of the mammalian intestinal telocyte niche","authors":"Daxin Jiang, Guoli Zhu, Yongchao Zhang, Jiawen Wang, Nannan Qian, Zhen Jin, Qingyu Sun, Haimeng Yu, Kebei Tang, Tao Cai, Fengchao Wang, Rongwen Xi","doi":"10.1016/j.devcel.2025.09.004","DOIUrl":"https://doi.org/10.1016/j.devcel.2025.09.004","url":null,"abstract":"Intestinal telocytes that reside immediately beneath the intestinal epithelium exert niche-supporting roles for intestinal stem cells and their progenies. They are heterogeneous cells compartmentalized along the crypt-villus axis, but the mechanisms governing the maintenance of this telocyte population remain unclear. Here, we identify a distinct population of subepithelial mesenchymal cells in the developing mouse embryo, marked by <em>LIM Domain Only 3</em> (<em>Lmo3</em>), as the cellular origin of post-natal intestinal telocytes. The <em>Lmo3</em><sup><em>+</em></sup> cells emerge prior to villus formation at embryonic day 13.5, and after birth, they progressively acquire a spatial confinement to the intestinal isthmus region, where they persist as long-lived, slow-cycling cells, supplying both peri-villus and peri-crypt telocytes. Further, we show that <em>Lmo3</em><sup>+</sup> cells respond rapidly to tissue damage, becoming activated to promote repair of the telocyte niche. Therefore, a quiescent and damage-responsive progenitor cell population marked by <em>Lmo3</em> maintains the intestinal telocyte niche.","PeriodicalId":11157,"journal":{"name":"Developmental cell","volume":"94 1","pages":""},"PeriodicalIF":11.8,"publicationDate":"2025-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145141185","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}
引用次数: 0
Cryo-EM structure and dynamic basis of phosphate uptake by PHT1 in rice 水稻PHT1吸收磷素的低温电镜结构和动态基础
IF 11.8 1区 生物学 Q1 CELL BIOLOGY Pub Date : 2025-09-25 DOI: 10.1016/j.devcel.2025.09.003
Zhangmeng Du, Zeyuan Guan, Hai Liu, Jie Zhang, Haitao He, Zhiwen Zheng, Wenhui Zhang, Lihuan Jiang, Jiaqi Zuo, Yan Liu, Beijing Wan, Haifu Tu, Faming Dong, Xuelei Lai, Lizhong Xiong, Ping Yin, Shaowu Xue, Yanke Chen, Zhu Liu
Phosphorus is an essential macronutrient for plants, primarily absorbed from the soil as inorganic phosphate (Pi) through root-located Pi transporters. Despite decades of research into these transporters as targets for developing Pi-efficient crops, their mechanisms for Pi import remain poorly understood. Here, we present the cryo-electron microscopy (cryo-EM) structures of the rice Pi importer OsPHT1;11 in both Pi-bound and unbound forms, characterize its conformational dynamics, and demonstrate how these dynamics contribute to its transport function. Pi is recognized through conserved residues found in plants, with its translocation facilitated by a typical alternating-access mechanism. Single-molecule fluorescence resonance energy transfer (smFRET) analyses show that this transporter undergoes dynamic conformational fluctuations, which are differentially linked to its Pi transport capability, with a predominance of extracellular open conformations favoring Pi transport, while more populated intracellular open conformations hinder it. These findings highlight key conformational determinants of transport activity and provide mechanistic insights into Pi uptake in plants.
磷是植物必需的大量营养元素,主要通过根系转运体以无机磷酸盐的形式从土壤中吸收。尽管对这些转运体作为开发高效Pi作物的目标进行了数十年的研究,但它们进口Pi的机制仍然知之甚少。在这里,我们展示了水稻Pi进口商OsPHT1的低温电镜(cryo-EM)结构;11在pi束缚和非束缚形式下,表征其构象动力学,并证明这些动力学如何促进其传递功能。Pi是通过在植物中发现的保守残基来识别的,它的易位是通过典型的交替通路机制来促进的。单分子荧光共振能量转移(smFRET)分析表明,这种转运体经历了动态构象波动,这与它的Pi转运能力有不同的联系,细胞外开放构象的优势有利于Pi转运,而更多的细胞内开放构象阻碍了Pi转运。这些发现突出了运输活性的关键构象决定因素,并为植物的Pi摄取提供了机制见解。
{"title":"Cryo-EM structure and dynamic basis of phosphate uptake by PHT1 in rice","authors":"Zhangmeng Du, Zeyuan Guan, Hai Liu, Jie Zhang, Haitao He, Zhiwen Zheng, Wenhui Zhang, Lihuan Jiang, Jiaqi Zuo, Yan Liu, Beijing Wan, Haifu Tu, Faming Dong, Xuelei Lai, Lizhong Xiong, Ping Yin, Shaowu Xue, Yanke Chen, Zhu Liu","doi":"10.1016/j.devcel.2025.09.003","DOIUrl":"https://doi.org/10.1016/j.devcel.2025.09.003","url":null,"abstract":"Phosphorus is an essential macronutrient for plants, primarily absorbed from the soil as inorganic phosphate (Pi) through root-located Pi transporters. Despite decades of research into these transporters as targets for developing Pi-efficient crops, their mechanisms for Pi import remain poorly understood. Here, we present the cryo-electron microscopy (cryo-EM) structures of the rice Pi importer OsPHT1;11 in both Pi-bound and unbound forms, characterize its conformational dynamics, and demonstrate how these dynamics contribute to its transport function. Pi is recognized through conserved residues found in plants, with its translocation facilitated by a typical alternating-access mechanism. Single-molecule fluorescence resonance energy transfer (smFRET) analyses show that this transporter undergoes dynamic conformational fluctuations, which are differentially linked to its Pi transport capability, with a predominance of extracellular open conformations favoring Pi transport, while more populated intracellular open conformations hinder it. These findings highlight key conformational determinants of transport activity and provide mechanistic insights into Pi uptake in plants.","PeriodicalId":11157,"journal":{"name":"Developmental cell","volume":"193 1","pages":""},"PeriodicalIF":11.8,"publicationDate":"2025-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145140955","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}
引用次数: 0
Maternal CENP-C restores centromere symmetry in mammalian zygotes to ensure proper chromosome segregation 母体CENP-C恢复哺乳动物受精卵的着丝粒对称性,以确保适当的染色体分离
IF 11.8 1区 生物学 Q1 CELL BIOLOGY Pub Date : 2025-09-24 DOI: 10.1016/j.devcel.2025.08.017
Catherine A. Tower, Gabriel Manske, Emily L. Ferrell, Dilara N. Anbarci, Kelsey Jorgensen, Binbin Ma, Mansour Aboelenain, Rajesh Ranjan, Saikat Chakraborty, Lindsay Moritz, Arunika Das, Michele Boiani, Ben E. Black, Shawn Chavez, Erica E. Marsh, Ariella Shikanov, Karen Schindler, Xin Chen, Saher Sue Hammoud
Across metazoan species, the centromere-specific histone variant CENP-A is essential for accurate chromosome segregation, yet its regulation during the mammalian parental-to-zygote transition is poorly understood. To address this, we generated a CENP-A-mScarlet mouse model that revealed sex-specific dynamics: mature sperm retain 10% of the CENP-A levels present in MII oocytes. However, this difference is resolved in zygotes prior to the first mitosis, using maternally inherited cytoplasmic CENP-A. Notably, the increase in CENP-A at paternal centromeres is independent of sensing CENP-A asymmetry or the presence of maternal chromosomes. Instead, CENP-A equalization relies on the asymmetric recruitment of maternal CENP-C to paternal centromeres. Depletion of maternal CENP-A decreases total CENP-A in both pronuclei without disrupting equalization. In contrast, reducing maternal CENP-C or disruption of its dimerization function impairs CENP-A equalization and chromosome segregation. Therefore, maternal CENP-C acts as a key epigenetic regulator that resets centromeric symmetry at fertilization to preserve genome integrity.
在后生动物物种中,着丝粒特异性组蛋白变体CENP-A对于准确的染色体分离至关重要,但其在哺乳动物亲本到受精卵转变过程中的调控作用尚不清楚。为了解决这个问题,我们建立了一个揭示性别特异性动态的CENP-A- mscarlet小鼠模型:成熟精子保留了MII卵母细胞中存在的10%的CENP-A水平。然而,这种差异在第一次有丝分裂之前在受精卵中被解决,使用母体遗传的细胞质CENP-A。值得注意的是,父本着丝粒中CENP-A的增加与感知CENP-A不对称或母体染色体的存在无关。相反,CENP-A的均衡依赖于母体CENP-C向父亲着丝粒的不对称募集。母体CENP-A的耗竭减少了两个原核的总CENP-A,但不破坏平衡。相反,母体CENP-C的减少或其二聚化功能的破坏会损害CENP-A的均衡和染色体分离。因此,母体的CENP-C作为一个关键的表观遗传调节因子,在受精时重置着丝粒对称性,以保持基因组的完整性。
{"title":"Maternal CENP-C restores centromere symmetry in mammalian zygotes to ensure proper chromosome segregation","authors":"Catherine A. Tower, Gabriel Manske, Emily L. Ferrell, Dilara N. Anbarci, Kelsey Jorgensen, Binbin Ma, Mansour Aboelenain, Rajesh Ranjan, Saikat Chakraborty, Lindsay Moritz, Arunika Das, Michele Boiani, Ben E. Black, Shawn Chavez, Erica E. Marsh, Ariella Shikanov, Karen Schindler, Xin Chen, Saher Sue Hammoud","doi":"10.1016/j.devcel.2025.08.017","DOIUrl":"https://doi.org/10.1016/j.devcel.2025.08.017","url":null,"abstract":"Across metazoan species, the centromere-specific histone variant CENP-A is essential for accurate chromosome segregation, yet its regulation during the mammalian parental-to-zygote transition is poorly understood. To address this, we generated a CENP-A-mScarlet mouse model that revealed sex-specific dynamics: mature sperm retain 10% of the CENP-A levels present in MII oocytes. However, this difference is resolved in zygotes prior to the first mitosis, using maternally inherited cytoplasmic CENP-A. Notably, the increase in CENP-A at paternal centromeres is independent of sensing CENP-A asymmetry or the presence of maternal chromosomes. Instead, CENP-A equalization relies on the asymmetric recruitment of maternal CENP-C to paternal centromeres. Depletion of maternal CENP-A decreases total CENP-A in both pronuclei without disrupting equalization. In contrast, reducing maternal CENP-C or disruption of its dimerization function impairs CENP-A equalization and chromosome segregation. Therefore, maternal CENP-C acts as a key epigenetic regulator that resets centromeric symmetry at fertilization to preserve genome integrity.","PeriodicalId":11157,"journal":{"name":"Developmental cell","volume":"11 1","pages":""},"PeriodicalIF":11.8,"publicationDate":"2025-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145127337","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}
引用次数: 0
期刊
Developmental cell
全部 Acc. Chem. Res. ACS Applied Bio Materials ACS Appl. Electron. Mater. ACS Appl. Energy Mater. ACS Appl. Mater. Interfaces ACS Appl. Nano Mater. ACS Appl. Polym. Mater. ACS BIOMATER-SCI ENG ACS Catal. ACS Cent. Sci. ACS Chem. Biol. ACS Chemical Health & Safety ACS Chem. Neurosci. ACS Comb. Sci. ACS Earth Space Chem. ACS Energy Lett. ACS Infect. Dis. ACS Macro Lett. ACS Mater. Lett. ACS Med. Chem. Lett. ACS Nano ACS Omega ACS Photonics ACS Sens. ACS Sustainable Chem. Eng. ACS Synth. Biol. Anal. Chem. BIOCHEMISTRY-US Bioconjugate Chem. BIOMACROMOLECULES Chem. Res. Toxicol. Chem. Rev. Chem. Mater. CRYST GROWTH DES ENERG FUEL Environ. Sci. Technol. Environ. Sci. Technol. Lett. Eur. J. Inorg. Chem. IND ENG CHEM RES Inorg. Chem. J. Agric. Food. Chem. J. Chem. Eng. Data J. Chem. Educ. J. Chem. Inf. Model. J. Chem. Theory Comput. J. Med. Chem. J. Nat. Prod. J PROTEOME RES J. Am. Chem. Soc. LANGMUIR MACROMOLECULES Mol. Pharmaceutics Nano Lett. Org. Lett. ORG PROCESS RES DEV ORGANOMETALLICS J. Org. Chem. J. Phys. Chem. J. Phys. Chem. A J. Phys. Chem. B J. Phys. Chem. C J. Phys. Chem. Lett. Analyst Anal. Methods Biomater. Sci. Catal. Sci. Technol. Chem. Commun. Chem. Soc. Rev. CHEM EDUC RES PRACT CRYSTENGCOMM Dalton Trans. Energy Environ. Sci. ENVIRON SCI-NANO ENVIRON SCI-PROC IMP ENVIRON SCI-WAT RES Faraday Discuss. Food Funct. Green Chem. Inorg. Chem. Front. Integr. Biol. J. Anal. At. Spectrom. J. Mater. Chem. A J. Mater. Chem. B J. Mater. Chem. C Lab Chip Mater. Chem. Front. Mater. Horiz. MEDCHEMCOMM Metallomics Mol. Biosyst. Mol. Syst. Des. Eng. Nanoscale Nanoscale Horiz. Nat. Prod. Rep. New J. Chem. Org. Biomol. Chem. Org. Chem. Front. PHOTOCH PHOTOBIO SCI PCCP Polym. Chem.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
0
微信
客服QQ
Book学术公众号 扫码关注我们
反馈
×
意见反馈
请填写您的意见或建议
请填写您的手机或邮箱
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
现在去查看 取消
×
提示
确定
Book学术官方微信
Book学术文献互助
Book学术文献互助群
群 号:604180095
Book学术
文献互助 智能选刊 最新文献 互助须知 联系我们:info@booksci.cn
Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。
Copyright © 2023 Book学术 All rights reserved.
ghs 京公网安备 11010802042870号 京ICP备2023020795号-1