Nature Cell Biology最新文献_第4页

Retinoid-enhanced human gastruloids 维甲酸增强型人类胃泌素

IF 17.3 1区生物学

Nature Cell Biology Pub Date : 2024-10-10 DOI: 10.1038/s41556-024-01517-5

Alexandra Schauer, Jesse V. Veenvliet

引用次数: 0

Spatial and functional separation of mTORC1 signalling in response to different amino acid sources mTORC1 信号对不同氨基酸源的响应在空间和功能上的分离

IF 21.3 1区生物学

Nature Cell Biology Pub Date : 2024-10-09 DOI: 10.1038/s41556-024-01523-7

Stephanie A. Fernandes, Danai-Dimitra Angelidaki, Julian Nüchel, Jiyoung Pan, Peter Gollwitzer, Yoav Elkis, Filippo Artoni, Sabine Wilhelm, Marija Kovacevic-Sarmiento, Constantinos Demetriades

{"title":"Spatial and functional separation of mTORC1 signalling in response to different amino acid sources","authors":"Stephanie A. Fernandes, Danai-Dimitra Angelidaki, Julian Nüchel, Jiyoung Pan, Peter Gollwitzer, Yoav Elkis, Filippo Artoni, Sabine Wilhelm, Marija Kovacevic-Sarmiento, Constantinos Demetriades","doi":"10.1038/s41556-024-01523-7","DOIUrl":"https://doi.org/10.1038/s41556-024-01523-7","url":null,"abstract":"Amino acid (AA) availability is a robust determinant of cell growth through controlling mechanistic/mammalian target of rapamycin complex 1 (mTORC1) activity. According to the predominant model in the field, AA sufficiency drives the recruitment and activation of mTORC1 on the lysosomal surface by the heterodimeric Rag GTPases, from where it coordinates the majority of cellular processes. Importantly, however, the teleonomy of the proposed lysosomal regulation of mTORC1 and where mTORC1 acts on its effector proteins remain enigmatic. Here, by using multiple pharmacological and genetic means to perturb the lysosomal AA-sensing and protein recycling machineries, we describe the spatial separation of mTORC1 regulation and downstream functions in mammalian cells, with lysosomal and non-lysosomal mTORC1 phosphorylating distinct substrates in response to different AA sources. Moreover, we reveal that a fraction of mTOR localizes at lysosomes owing to basal lysosomal proteolysis that locally supplies new AAs, even in cells grown in the presence of extracellular nutrients, whereas cytoplasmic mTORC1 is regulated by exogenous AAs. Overall, our study substantially expands our knowledge about the topology of mTORC1 regulation by AAs and hints at the existence of distinct, Rag- and lysosome-independent mechanisms that control its activity at other subcellular locations. Given the importance of mTORC1 signalling and AA sensing for human ageing and disease, our findings will probably pave the way towards the identification of function-specific mTORC1 regulators and thus highlight more effective targets for drug discovery against conditions with dysregulated mTORC1 activity in the future.","PeriodicalId":18977,"journal":{"name":"Nature Cell Biology","volume":null,"pages":null},"PeriodicalIF":21.3,"publicationDate":"2024-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142385116","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

Blood-generating heart-forming organoids recapitulate co-development of the human haematopoietic system and the embryonic heart 造血心脏形成器官再现了人类造血系统和胚胎心脏的共同发育过程

IF 21.3 1区生物学

Nature Cell Biology Pub Date : 2024-10-08 DOI: 10.1038/s41556-024-01526-4

Miriana Dardano, Felix Kleemiß, Maike Kosanke, Dorina Lang, Liam Wilson, Annika Franke, Jana Teske, Akshatha Shivaraj, Jeanne de la Roche, Martin Fischer, Lucas Lange, Axel Schambach, Lika Drakhlis, Robert Zweigerdt

{"title":"Blood-generating heart-forming organoids recapitulate co-development of the human haematopoietic system and the embryonic heart","authors":"Miriana Dardano, Felix Kleemiß, Maike Kosanke, Dorina Lang, Liam Wilson, Annika Franke, Jana Teske, Akshatha Shivaraj, Jeanne de la Roche, Martin Fischer, Lucas Lange, Axel Schambach, Lika Drakhlis, Robert Zweigerdt","doi":"10.1038/s41556-024-01526-4","DOIUrl":"https://doi.org/10.1038/s41556-024-01526-4","url":null,"abstract":"Despite the biomedical importance of haematopoietic stem cells and haematopoietic progenitor cells, their in vitro stabilization in a developmental context has not been achieved due to limited knowledge of signals and markers specifying the multiple haematopoietic waves as well as ethically restricted access to the human embryo. Thus, an in vitro approach resembling aspects of haematopoietic development in the context of neighbouring tissues is of interest. Our established human pluripotent stem cell-derived heart-forming organoids (HFOs) recapitulate aspects of heart, vasculature and foregut co-development. Modulating HFO differentiation, we here report the generation of blood-generating HFOs. While maintaining a functional ventricular-like heart anlagen, blood-generating HFOs comprise a mesenchyme-embedded haemogenic endothelial layer encompassing multiple haematopoietic derivatives and haematopoietic progenitor cells with erythro-myeloid and lymphoid potential, reflecting aspects of primitive and definitive haematopoiesis. The model enables the morphologically structured co-development of cardiac, endothelial and multipotent haematopoietic tissues equivalent to the intra-embryonic haematopoietic region in vivo, promoting research on haematopoiesis in vitro.","PeriodicalId":18977,"journal":{"name":"Nature Cell Biology","volume":null,"pages":null},"PeriodicalIF":21.3,"publicationDate":"2024-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142384362","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

ARF1 compartments direct cargo flow via maturation into recycling endosomes ARF1 区室通过成熟为循环内体引导货物流动

IF 21.3 1区生物学

Nature Cell Biology Pub Date : 2024-10-04 DOI: 10.1038/s41556-024-01518-4

Alexander Stockhammer, Petia Adarska, Vini Natalia, Anja Heuhsen, Antonia Klemt, Gresy Bregu, Shelly Harel, Carmen Rodilla-Ramirez, Carissa Spalt, Ece Özsoy, Paula Leupold, Alica Grindel, Eleanor Fox, Joy Orezimena Mejedo, Amin Zehtabian, Helge Ewers, Dmytro Puchkov, Volker Haucke, Francesca Bottanelli

{"title":"ARF1 compartments direct cargo flow via maturation into recycling endosomes","authors":"Alexander Stockhammer, Petia Adarska, Vini Natalia, Anja Heuhsen, Antonia Klemt, Gresy Bregu, Shelly Harel, Carmen Rodilla-Ramirez, Carissa Spalt, Ece Özsoy, Paula Leupold, Alica Grindel, Eleanor Fox, Joy Orezimena Mejedo, Amin Zehtabian, Helge Ewers, Dmytro Puchkov, Volker Haucke, Francesca Bottanelli","doi":"10.1038/s41556-024-01518-4","DOIUrl":"https://doi.org/10.1038/s41556-024-01518-4","url":null,"abstract":"Cellular membrane homoeostasis is maintained via a tightly regulated membrane and cargo flow between organelles of the endocytic and secretory pathways. Adaptor protein complexes (APs), which are recruited to membranes by the small GTPase ARF1, facilitate cargo selection and incorporation into trafficking intermediates. According to the classical model, small vesicles would facilitate bi-directional long-range transport between the Golgi, endosomes and plasma membrane. Here we revisit the intracellular organization of the vesicular transport machinery using a combination of CRISPR-Cas9 gene editing, live-cell high temporal (fast confocal) or spatial (stimulated emission depletion) microscopy as well as correlative light and electron microscopy. We characterize tubulo-vesicular ARF1 compartments that harbour clathrin and different APs. Our findings reveal two functionally different classes of ARF1 compartments, each decorated by a different combination of APs. Perinuclear ARF1 compartments facilitate Golgi export of secretory cargo, while peripheral ARF1 compartments are involved in endocytic recycling downstream of early endosomes. Contrary to the classical model of long-range vesicle shuttling, we observe that ARF1 compartments shed ARF1 and mature into recycling endosomes. This maturation process is impaired in the absence of AP-1 and results in trafficking defects. Collectively, these data highlight a crucial role for ARF1 compartments in post-Golgi sorting.","PeriodicalId":18977,"journal":{"name":"Nature Cell Biology","volume":null,"pages":null},"PeriodicalIF":21.3,"publicationDate":"2024-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142370043","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

Recording morphogen signals reveals mechanisms underlying gastruloid symmetry breaking 记录形态发生器信号揭示胃肠对称破缺的内在机制

IF 21.3 1区生物学

Nature Cell Biology Pub Date : 2024-10-02 DOI: 10.1038/s41556-024-01521-9

Harold M. McNamara, Sabrina C. Solley, Britt Adamson, Michelle M. Chan, Jared E. Toettcher

{"title":"Recording morphogen signals reveals mechanisms underlying gastruloid symmetry breaking","authors":"Harold M. McNamara, Sabrina C. Solley, Britt Adamson, Michelle M. Chan, Jared E. Toettcher","doi":"10.1038/s41556-024-01521-9","DOIUrl":"https://doi.org/10.1038/s41556-024-01521-9","url":null,"abstract":"Aggregates of stem cells can break symmetry and self-organize into embryo-like structures with complex morphologies and gene expression patterns. Mechanisms including reaction-diffusion Turing patterns and cell sorting have been proposed to explain symmetry breaking but distinguishing between these candidate mechanisms of self-organization requires identifying which early asymmetries evolve into subsequent tissue patterns and cell fates. Here we use synthetic ‘signal-recording’ gene circuits to trace the evolution of signalling patterns in gastruloids, three-dimensional stem cell aggregates that form an anterior–posterior axis and structures resembling the mammalian primitive streak and tailbud. We find that cell sorting rearranges patchy domains of Wnt activity into a single pole that defines the gastruloid anterior–posterior axis. We also trace the emergence of Wnt domains to earlier heterogeneity in Nodal activity even before Wnt activity is detectable. Our study defines a mechanism through which aggregates of stem cells can form a patterning axis even in the absence of external spatial cues.","PeriodicalId":18977,"journal":{"name":"Nature Cell Biology","volume":null,"pages":null},"PeriodicalIF":21.3,"publicationDate":"2024-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142362786","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

The role of PINK1–Parkin in mitochondrial quality control PINK1-Parkin 在线粒体质量控制中的作用

IF 17.3 1区生物学

Nature Cell Biology Pub Date : 2024-10-02 DOI: 10.1038/s41556-024-01513-9

Derek P. Narendra, Richard J. Youle

引用次数: 0

RNAs kiss and translate in germ granules RNA 在胚芽颗粒中接吻和翻译

IF 21.3 1区生物学

Nature Cell Biology Pub Date : 2024-10-01 DOI: 10.1038/s41556-024-01502-y

Ameya P. Jalihal, Zachary M. Geisterfer, Amy S. Gladfelter

引用次数: 0

HERD-1 mediates multiphase condensate immiscibility to regulate small RNA-driven transgenerational epigenetic inheritance HERD-1介导多相凝结物不溶性，调节小核糖核酸驱动的转代表观遗传

IF 21.3 1区生物学

Nature Cell Biology Pub Date : 2024-10-01 DOI: 10.1038/s41556-024-01514-8

Changfeng Zhao, Shiyu Cai, Ruona Shi, Xinru Li, Boyuan Deng, Ruofei Li, Shuhan Yang, Jing Huang, Yonglin Liang, Pu Lu, Zhongping Yuan, Haoxiang Jia, Zongjin Jiang, Xiaofei Zhang, Scott Kennedy, Gang Wan

{"title":"HERD-1 mediates multiphase condensate immiscibility to regulate small RNA-driven transgenerational epigenetic inheritance","authors":"Changfeng Zhao, Shiyu Cai, Ruona Shi, Xinru Li, Boyuan Deng, Ruofei Li, Shuhan Yang, Jing Huang, Yonglin Liang, Pu Lu, Zhongping Yuan, Haoxiang Jia, Zongjin Jiang, Xiaofei Zhang, Scott Kennedy, Gang Wan","doi":"10.1038/s41556-024-01514-8","DOIUrl":"https://doi.org/10.1038/s41556-024-01514-8","url":null,"abstract":"Biomolecular condensates, such as the nucleolus, stress granules/processing bodies and germ granules, are multiphase assemblages whose formation mechanisms and significance remain poorly understood. Here we identify protein constituents of the spatiotemporally ordered P, Z and M multiphase condensates in Caenorhabditis elegans germ granules using optimized TurboID-mediated proximity biotin labelling. These include 462, 41 and 86 proteins localizing to P, Z and M condensates, respectively, of which 522 were previously unknown protein constituents. Each condensate’s proteins are enriched for distinct classes of structured and intrinsically disordered domains, suggesting divergent functions and assembly mechanisms. Through a functional screen, we identify a germ granule protein, HERD-1, which prevents the mixing of P, Z and M condensates. Mixing in herd-1 mutants correlates with disorganization of germline small RNA pathways and prolonged epigenetic inheritance of RNA interference-induced gene silencing. Forced mixing of these condensate components using a nanobody with specific binding activity against green fluorescent protein also extends epigenetic inheritance. We propose that active maintenance of germ granule immiscibility helps to organize and regulate small RNA-driven transgenerational epigenetic inheritance in C. elegans.","PeriodicalId":18977,"journal":{"name":"Nature Cell Biology","volume":null,"pages":null},"PeriodicalIF":21.3,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142330378","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

An architectural role of specific RNA–RNA interactions in oskar granules 奥斯卡颗粒中特定 RNA-RNA 相互作用的结构作用

IF 21.3 1区生物学

Nature Cell Biology Pub Date : 2024-10-01 DOI: 10.1038/s41556-024-01519-3

Mainak Bose, Branislava Rankovic, Julia Mahamid, Anne Ephrussi

{"title":"An architectural role of specific RNA–RNA interactions in oskar granules","authors":"Mainak Bose, Branislava Rankovic, Julia Mahamid, Anne Ephrussi","doi":"10.1038/s41556-024-01519-3","DOIUrl":"https://doi.org/10.1038/s41556-024-01519-3","url":null,"abstract":"Ribonucleoprotein (RNP) granules are membraneless condensates that organize the intracellular space by compartmentalization of specific RNAs and proteins. Studies have shown that RNA tunes the phase behaviour of RNA-binding proteins, but the role of intermolecular RNA–RNA interactions in RNP granules in vivo remains less explored. Here we determine the role of a sequence-specific RNA–RNA kissing-loop interaction in assembly of mesoscale oskar RNP granules in the female Drosophila germline. We show that a two-nucleotide mutation that disrupts kissing-loop-mediated oskar messenger RNA dimerization impairs condensate formation in vitro and oskar granule assembly in the developing oocyte, leading to defective posterior localization of the RNA and abrogation of oskar-associated processing bodies upon nutritional stress. This specific trans RNA–RNA interaction acts synergistically with the scaffold RNA-binding protein, Bruno, in driving condensate assembly. Our study highlights the architectural contribution of an mRNA and its specific secondary structure and tertiary interactions to the formation of an RNP granule that is essential for embryonic development.","PeriodicalId":18977,"journal":{"name":"Nature Cell Biology","volume":null,"pages":null},"PeriodicalIF":21.3,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142330377","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

Astrocytes are enablers of brain metastases 星形胶质细胞是脑转移的助推器

IF 17.3 1区生物学

Nature Cell Biology Pub Date : 2024-09-30 DOI: 10.1038/s41556-024-01516-6

Livia Garzia

引用次数: 0