Nature Cell Biology最新文献_第7页

Mitophagy protects against ferroptosis 有丝分裂可防止铁蛋白沉积症

IF 17.3 1区生物学

Nature Cell Biology Pub Date : 2024-09-12 DOI: 10.1038/s41556-024-01507-7

Petra Gross

引用次数: 0

Solid tumour-induced systemic immunosuppression involves dichotomous myeloid–B cell interactions 实体瘤诱导的全身免疫抑制涉及二分法髓系-B 细胞相互作用

IF 17.3 1区生物学

Nature Cell Biology Pub Date : 2024-09-12 DOI: 10.1038/s41556-024-01508-6

Xiaoxin Hao, Yichao Shen, Jun Liu, Angela Alexander, Ling Wu, Zhan Xu, Liqun Yu, Yang Gao, Fengshuo Liu, Hilda L. Chan, Che-Hsing Li, Yunfeng Ding, Weijie Zhang, David G. Edwards, Nan Chen, Azadeh Nasrazadani, Naoto T. Ueno, Bora Lim, Xiang H.-F. Zhang

{"title":"Solid tumour-induced systemic immunosuppression involves dichotomous myeloid–B cell interactions","authors":"Xiaoxin Hao, Yichao Shen, Jun Liu, Angela Alexander, Ling Wu, Zhan Xu, Liqun Yu, Yang Gao, Fengshuo Liu, Hilda L. Chan, Che-Hsing Li, Yunfeng Ding, Weijie Zhang, David G. Edwards, Nan Chen, Azadeh Nasrazadani, Naoto T. Ueno, Bora Lim, Xiang H.-F. Zhang","doi":"10.1038/s41556-024-01508-6","DOIUrl":"10.1038/s41556-024-01508-6","url":null,"abstract":"Solid tumours induce systemic immunosuppression that involves myeloid and T cells. B cell-related mechanisms remain relatively understudied. Here we discover two distinct patterns of tumour-induced B cell abnormality (TiBA; TiBA-1 and TiBA-2), both associated with abnormal myelopoiesis in the bone marrow. TiBA-1 probably results from the niche competition between pre-progenitor-B cells and myeloid progenitors, leading to a global reduction in downstream B cells. TiBA-2 is characterized by systemic accumulation of a unique early B cell population, driven by interaction with excessive neutrophils. Importantly, TiBA-2-associated early B cells foster the systemic accumulation of exhaustion-like T cells. Myeloid and B cells from the peripheral blood of patients with triple-negative breast cancer recapitulate the TiBA subtypes, and the distinct TiBA profile correlates with pathologic complete responses to standard-of-care immunotherapy. This study underscores the inter-patient diversity of tumour-induced systemic changes and emphasizes the need for treatments tailored to different B and myeloid cell abnormalities. Hao, Shen and colleagues identify and characterize two distinct types of myeloid–B cell interaction that may signal solid tumour-induced immunosuppression and can correlate with complete responses to immunotherapy in patients with breast cancer.","PeriodicalId":18977,"journal":{"name":"Nature Cell Biology","volume":"26 11","pages":"1971-1983"},"PeriodicalIF":17.3,"publicationDate":"2024-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142170869","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

Ferroptosis disseminates afar in development 铁蛋白沉积症在发育过程中四处扩散

IF 17.3 1区生物学

Nature Cell Biology Pub Date : 2024-09-12 DOI: 10.1038/s41556-024-01504-w

Zhe Wang

引用次数: 0

Profiling cell death in COVID-19 pathology 剖析 COVID-19 病理学中的细胞死亡

IF 17.3 1区生物学

Nature Cell Biology Pub Date : 2024-09-12 DOI: 10.1038/s41556-024-01505-9

Zhe Wang

引用次数: 0

The Polycomb system sustains promoters in a deep OFF state by limiting pre-initiation complex formation to counteract transcription 多角体系统通过限制启动前复合物的形成来抵消转录，从而使启动子处于深度关闭状态

IF 17.3 1区生物学

Nature Cell Biology Pub Date : 2024-09-11 DOI: 10.1038/s41556-024-01493-w

Aleksander T. Szczurek, Emilia Dimitrova, Jessica R. Kelley, Neil P. Blackledge, Robert J. Klose

{"title":"The Polycomb system sustains promoters in a deep OFF state by limiting pre-initiation complex formation to counteract transcription","authors":"Aleksander T. Szczurek, Emilia Dimitrova, Jessica R. Kelley, Neil P. Blackledge, Robert J. Klose","doi":"10.1038/s41556-024-01493-w","DOIUrl":"10.1038/s41556-024-01493-w","url":null,"abstract":"The Polycomb system has fundamental roles in regulating gene expression during mammalian development. However, how it controls transcription to enable gene repression has remained enigmatic. Here, using rapid degron-based depletion coupled with live-cell transcription imaging and single-particle tracking, we show how the Polycomb system controls transcription in single cells. We discover that the Polycomb system is not a constitutive block to transcription but instead sustains a long-lived deep promoter OFF state, which limits the frequency with which the promoter can enter into a transcribing state. We demonstrate that Polycomb sustains this deep promoter OFF state by counteracting the binding of factors that enable early transcription pre-initiation complex formation and show that this is necessary for gene repression. Together, these important discoveries provide a rationale for how the Polycomb system controls transcription and suggests a universal mechanism that could enable the Polycomb system to constrain transcription across diverse cellular contexts. Combining degron-based depletion with live-cell transcription imaging and single-particle tracking, Szczurek et al. show that Polycomb keeps promoters in an OFF state by restricting the formation of the pre-initiation complex.","PeriodicalId":18977,"journal":{"name":"Nature Cell Biology","volume":"26 10","pages":"1700-1711"},"PeriodicalIF":17.3,"publicationDate":"2024-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41556-024-01493-w.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142170870","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Ammonia-induced lysosomal and mitochondrial damage causes cell death of effector CD8+ T cells 氨诱导的溶酶体和线粒体损伤导致效应 CD8+ T 细胞死亡

IF 17.3 1区生物学

Nature Cell Biology Pub Date : 2024-09-11 DOI: 10.1038/s41556-024-01503-x

Huafeng Zhang, Jincheng Liu, Wu Yuan, Qian Zhang, Xiao Luo, Yonggang Li, Yue’e Peng, Jingyu Feng, Xiaoyu Liu, Jie Chen, Yabo Zhou, Jiadi Lv, Nannan Zhou, Jingwei Ma, Ke Tang, Bo Huang

{"title":"Ammonia-induced lysosomal and mitochondrial damage causes cell death of effector CD8+ T cells","authors":"Huafeng Zhang, Jincheng Liu, Wu Yuan, Qian Zhang, Xiao Luo, Yonggang Li, Yue’e Peng, Jingyu Feng, Xiaoyu Liu, Jie Chen, Yabo Zhou, Jiadi Lv, Nannan Zhou, Jingwei Ma, Ke Tang, Bo Huang","doi":"10.1038/s41556-024-01503-x","DOIUrl":"10.1038/s41556-024-01503-x","url":null,"abstract":"Ammonia is thought to be a cytotoxin and its increase in the blood impairs cell function. However, whether and how this toxin triggers cell death under pathophysiological conditions remains unclear. Here we show that ammonia induces a distinct form of cell death in effector T cells. We found that rapidly proliferating T cells use glutaminolysis to release ammonia in the mitochondria, which is then translocated to and stored in the lysosomes. Excessive ammonia accumulation increases lysosomal pH and results in the termination of lysosomal ammonia storage and ammonia reflux into mitochondria, leading to mitochondrial damage and cell death, which is characterized by lysosomal alkalization, mitochondrial swelling and impaired autophagic flux. Inhibition of glutaminolysis or blocking lysosomal alkalization prevents ammonia-induced T cell death and improves T cell-based antitumour immunotherapy. These findings identify a distinct form of cell death that differs from previously known mechanisms. Zhang, Liu and colleagues identify and characterize cell death in rapidly proliferating CD8+ T cells resulting from excessive ammonia accumulation and subsequent lysosomal dysfunction and mitochondrial damage.","PeriodicalId":18977,"journal":{"name":"Nature Cell Biology","volume":"26 11","pages":"1892-1902"},"PeriodicalIF":17.3,"publicationDate":"2024-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142170871","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

Inverse blebs operate as hydraulic pumps during mouse blastocyst formation 在小鼠胚泡形成过程中，反向出血作为液压泵起作用

IF 17.3 1区生物学

Nature Cell Biology Pub Date : 2024-09-11 DOI: 10.1038/s41556-024-01501-z

Markus F. Schliffka, Julien G. Dumortier, Diane Pelzer, Arghyadip Mukherjee, Jean-Léon Maître

{"title":"Inverse blebs operate as hydraulic pumps during mouse blastocyst formation","authors":"Markus F. Schliffka, Julien G. Dumortier, Diane Pelzer, Arghyadip Mukherjee, Jean-Léon Maître","doi":"10.1038/s41556-024-01501-z","DOIUrl":"10.1038/s41556-024-01501-z","url":null,"abstract":"During preimplantation development, mouse embryos form a fluid-filled lumen. Pressurized fluid fractures cell–cell contacts and accumulates into pockets, which coarsen into a single lumen. How the embryo controls intercellular fluid movement during coarsening is unknown. Here we report inverse blebs growing into cells at adhesive contacts. Throughout the embryo we observed hundreds of inverse blebs, each filling with intercellular fluid and retracting within a minute. Inverse blebs grow due to pressure build-up resulting from fluid accumulation and cell–cell adhesion, which locally confines fluid. Inverse blebs retract due to actomyosin contraction, practically pushing fluid within the intercellular space. Importantly, inverse blebs occur infrequently at contacts formed by multiple cells, which effectively serve as fluid sinks. Manipulation of the embryo topology reveals that without sinks inverse blebs pump fluid into one another in futile cycles. We propose that inverse blebs operate as hydraulic pumps to promote luminal coarsening, thereby constituting an instrument used by cells to control fluid movement. Schliffka et al. show that in the early mouse embryo, hemispherical intrusions, or inverse blebs, grow into cells at cell–cell adhesion sites in response to luminal fluid accumulation and pressure build-up, and may serve as pumps moving fluid into hydraulic sinks.","PeriodicalId":18977,"journal":{"name":"Nature Cell Biology","volume":"26 10","pages":"1669-1677"},"PeriodicalIF":17.3,"publicationDate":"2024-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142170873","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

Perturbing TET2 condensation promotes aberrant genome-wide DNA methylation and curtails leukaemia cell growth 扰乱 TET2 凝聚可促进全基因组 DNA 甲基化异常并抑制白血病细胞生长

IF 17.3 1区生物学

Nature Cell Biology Pub Date : 2024-09-09 DOI: 10.1038/s41556-024-01496-7

Lei Guo, Tingting Hong, Yi-Tsang Lee, Xue Hu, Guokai Pan, Rongjie Zhao, Yuhan Yang, Jingwen Yang, Xiaoli Cai, Logan Rivera, Jie Liang, Rui Wang, Yaling Dou, Srikanth Kodali, Wenbo Li, Leng Han, Bruno Di Stefano, Yubin Zhou, Jia Li, Yun Huang

{"title":"Perturbing TET2 condensation promotes aberrant genome-wide DNA methylation and curtails leukaemia cell growth","authors":"Lei Guo, Tingting Hong, Yi-Tsang Lee, Xue Hu, Guokai Pan, Rongjie Zhao, Yuhan Yang, Jingwen Yang, Xiaoli Cai, Logan Rivera, Jie Liang, Rui Wang, Yaling Dou, Srikanth Kodali, Wenbo Li, Leng Han, Bruno Di Stefano, Yubin Zhou, Jia Li, Yun Huang","doi":"10.1038/s41556-024-01496-7","DOIUrl":"10.1038/s41556-024-01496-7","url":null,"abstract":"The ten-eleven translocation (TET) family of dioxygenases maintain stable local DNA demethylation during cell division and lineage specification. As the major catalytic product of TET enzymes, 5-hydroxymethylcytosine is selectively enriched at specific genomic regions, such as enhancers, in a tissue-dependent manner. However, the mechanisms underlying this selectivity remain unresolved. Here we unveil a low-complexity insert domain within TET2 that facilitates its biomolecular condensation with epigenetic modulators, such as UTX and MLL4. This co-condensation fosters a permissive chromatin environment for precise DNA demethylation. Disrupting low-complexity insert-mediated condensation alters the genomic binding of TET2 to cause promiscuous DNA demethylation and genome reorganization. These changes influence the expression of key genes implicated in leukaemogenesis to curtail leukaemia cell proliferation. Collectively, this study establishes the pivotal role of TET2 condensation in orchestrating precise DNA demethylation and gene transcription to support tumour cell growth. Guo, Hong et al. report that TET2 condensation maintains proper DNA demethylation at specific genomic loci, which can be targeted to alter gene expression and impair leukaemia growth.","PeriodicalId":18977,"journal":{"name":"Nature Cell Biology","volume":"26 12","pages":"2154-2167"},"PeriodicalIF":17.3,"publicationDate":"2024-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142158752","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

A size filter at the Golgi regulates apical membrane protein sorting 高尔基体上的尺寸过滤器调节顶端膜蛋白分拣

IF 17.3 1区生物学

Nature Cell Biology Pub Date : 2024-09-05 DOI: 10.1038/s41556-024-01500-0

Christian de Caestecker, Ian G. Macara

{"title":"A size filter at the Golgi regulates apical membrane protein sorting","authors":"Christian de Caestecker, Ian G. Macara","doi":"10.1038/s41556-024-01500-0","DOIUrl":"10.1038/s41556-024-01500-0","url":null,"abstract":"Despite decades of research, apical sorting of epithelial membrane proteins remains incompletely understood. We noted that apical cytoplasmic domains are smaller than those of basolateral proteins; however, the reason for this discrepancy is unknown. Here we used a synthetic biology approach to investigate whether a size barrier at the Golgi apparatus might hinder apical sorting of proteins with large cytoplasmic tails. We focused on Crb3, Ace2 and Muc1 as representative apical proteins with short cytoplasmic tails. By incorporating a streptavidin-binding peptide, these proteins can be trapped in the endoplasmic reticulum until addition of biotin, which triggers synchronous release to the Golgi and subsequent transport to the apical cortex. Strikingly, increasing the size of their cytoplasmic domains caused partial mislocalization to the basolateral cortex and significantly delayed Golgi departure. Moreover, N-glycosylation of ‘large’ Crb3 was delayed, and ‘small’ Crb3 segregated into spatially distinct Golgi regions. Biologically, Crb3 forms a complex through its cytoplasmic tail with the Pals1 protein, which could also delay departure, but although associated at the endoplasmic reticulum and Golgi, Pals1 disassociated before Crb3 departure. Notably, a non-dissociable mutant Pals1 hampered the exit of Crb3. We conclude that, unexpectedly, a size filter at the Golgi facilitates apical sorting of proteins with small cytoplasmic domains and that timely release of Pals1, to reduce cytoplasmic domain size, is essential for normal Crb3 sorting. de Caestecker and Macara study apical sorting of proteins with varying cytoplasmic tail length in epithelial cells. They propose that a size filter at the Golgi facilitates apical sorting of proteins with small cytoplasmic domains.","PeriodicalId":18977,"journal":{"name":"Nature Cell Biology","volume":"26 10","pages":"1678-1690"},"PeriodicalIF":17.3,"publicationDate":"2024-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142138031","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

Wnt-deficient and hypoxic environment orchestrates squamous reprogramming of human pancreatic ductal adenocarcinoma Wnt缺陷和缺氧环境协调人类胰腺导管腺癌的鳞状重塑

IF 17.3 1区生物学

Nature Cell Biology Pub Date : 2024-09-04 DOI: 10.1038/s41556-024-01498-5

Hiroki Tamagawa, Masayuki Fujii, Kazuhiro Togasaki, Takashi Seino, Shintaro Kawasaki, Ai Takano, Kohta Toshimitsu, Sirirat Takahashi, Yuki Ohta, Mami Matano, Kenta Kawasaki, Yujiro Machida, Shigeki Sekine, Akihito Machinaga, Ken Sasai, Yuzo Kodama, Nobuyuki Kakiuchi, Seishi Ogawa, Tomonori Hirano, Hiroshi Seno, Minoru Kitago, Yuko Kitagawa, Eisuke Iwasaki, Takanori Kanai, Toshiro Sato

{"title":"Wnt-deficient and hypoxic environment orchestrates squamous reprogramming of human pancreatic ductal adenocarcinoma","authors":"Hiroki Tamagawa, Masayuki Fujii, Kazuhiro Togasaki, Takashi Seino, Shintaro Kawasaki, Ai Takano, Kohta Toshimitsu, Sirirat Takahashi, Yuki Ohta, Mami Matano, Kenta Kawasaki, Yujiro Machida, Shigeki Sekine, Akihito Machinaga, Ken Sasai, Yuzo Kodama, Nobuyuki Kakiuchi, Seishi Ogawa, Tomonori Hirano, Hiroshi Seno, Minoru Kitago, Yuko Kitagawa, Eisuke Iwasaki, Takanori Kanai, Toshiro Sato","doi":"10.1038/s41556-024-01498-5","DOIUrl":"10.1038/s41556-024-01498-5","url":null,"abstract":"Human pancreatic cancer is characterized by the molecular diversity encompassing native duct-like and squamous cell-like identities, but mechanisms underlying squamous transdifferentiation have remained elusive. To comprehensively capture the molecular diversity of human pancreatic cancer, we here profiled 65 patient-derived pancreatic cancer organoid lines, including six adenosquamous carcinoma lines. H3K27me3-mediated erasure of the ductal lineage specifiers and hijacking of the TP63-driven squamous-cell programme drove squamous-cell commitment, providing survival benefit in a Wnt-deficient environment and hypoxic conditions. Gene engineering of normal pancreatic duct organoids revealed that GATA6 loss and a Wnt-deficient environment, in concert with genetic or hypoxia-mediated inactivation of KDM6A, facilitate squamous reprogramming, which in turn enhances environmental fitness. EZH2 inhibition counterbalanced the epigenetic bias and curbed the growth of adenosquamous cancer organoids. Our results demonstrate how an adversarial microenvironment dictates the molecular and histological evolution of human pancreatic cancer and provide insights into the principles and significance of lineage conversion in human cancer. Tamagawa, Fujii et al. demonstrate that squamous differentiation in human pancreatic cancer can be attributed to TP63-mediated lineage conversion and epigenetic reprogramming that depends upon a hypoxic and Wnt-defective niche.","PeriodicalId":18977,"journal":{"name":"Nature Cell Biology","volume":"26 10","pages":"1759-1772"},"PeriodicalIF":17.3,"publicationDate":"2024-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142130879","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