Pub Date : 2024-10-08DOI: 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
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. Dardano et al. generate human pluripotent stem cell-derived cardiac organoids capable of undergoing endothelial-to-haematopoietic transition and producing haematopoietic cells.
{"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":"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. Dardano et al. generate human pluripotent stem cell-derived cardiac organoids capable of undergoing endothelial-to-haematopoietic transition and producing haematopoietic cells.","PeriodicalId":18977,"journal":{"name":"Nature Cell Biology","volume":"26 11","pages":"1984-1996"},"PeriodicalIF":17.3,"publicationDate":"2024-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41556-024-01526-4.pdf","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":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-04DOI: 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
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. Stockhammer, Adarska et al. describe ARF1 compartments as the site of adaptor- and clathrin-dependent post-Golgi sorting. Shedding of ARF1 and maturation into recycling endosomes drives sorting of secretory and endocytic recycling cargo.
{"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":"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. Stockhammer, Adarska et al. describe ARF1 compartments as the site of adaptor- and clathrin-dependent post-Golgi sorting. Shedding of ARF1 and maturation into recycling endosomes drives sorting of secretory and endocytic recycling cargo.","PeriodicalId":18977,"journal":{"name":"Nature Cell Biology","volume":"26 11","pages":"1845-1859"},"PeriodicalIF":17.3,"publicationDate":"2024-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41556-024-01518-4.pdf","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":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-02DOI: 10.1038/s41556-024-01521-9
Harold M. McNamara, Sabrina C. Solley, Britt Adamson, Michelle M. Chan, Jared E. Toettcher
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. Toettcher, McNamara and colleagues use synthetic ‘signal-recording’ gene circuits on mouse gastruloids and find that cell sorting rearranges patchy domains of Wnt activity into a single pole, which defines the gastruloid anterior–posterior axis.
{"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":"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. Toettcher, McNamara and colleagues use synthetic ‘signal-recording’ gene circuits on mouse gastruloids and find that cell sorting rearranges patchy domains of Wnt activity into a single pole, which defines the gastruloid anterior–posterior axis.","PeriodicalId":18977,"journal":{"name":"Nature Cell Biology","volume":"26 11","pages":"1832-1844"},"PeriodicalIF":17.3,"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}
Pub Date : 2024-10-02DOI: 10.1038/s41556-024-01513-9
Derek P. Narendra, Richard J. Youle
Mitophagy mediated by the recessive Parkinson’s disease genes PINK1 and Parkin responds to mitochondrial damage to preserve mitochondrial function. In the pathway, PINK1 is the damage sensor, probing the integrity of the mitochondrial import pathway, and activating Parkin when import is blocked. Parkin is the effector, selectively marking damaged mitochondria with ubiquitin for mitophagy and other quality-control processes. This selective mitochondrial quality-control pathway may be especially critical for dopamine neurons affected in Parkinson’s disease, in which the mitochondrial network is widely distributed throughout a highly branched axonal arbor. Here we review the current understanding of the role of PINK1–Parkin in the quality control of mitophagy, including sensing of mitochondrial distress by PINK1, activation of Parkin by PINK1 to induce mitophagy, and the physiological relevance of the PINK1–Parkin pathway. Narendra and Youle review the current understanding of the role of PINK1–Parkin in the quality control of mitophagy, highlighting the underlying mechanisms and physiological relevance of the pathway, as well as its role in neuroprotection.
{"title":"The role of PINK1–Parkin in mitochondrial quality control","authors":"Derek P. Narendra, Richard J. Youle","doi":"10.1038/s41556-024-01513-9","DOIUrl":"10.1038/s41556-024-01513-9","url":null,"abstract":"Mitophagy mediated by the recessive Parkinson’s disease genes PINK1 and Parkin responds to mitochondrial damage to preserve mitochondrial function. In the pathway, PINK1 is the damage sensor, probing the integrity of the mitochondrial import pathway, and activating Parkin when import is blocked. Parkin is the effector, selectively marking damaged mitochondria with ubiquitin for mitophagy and other quality-control processes. This selective mitochondrial quality-control pathway may be especially critical for dopamine neurons affected in Parkinson’s disease, in which the mitochondrial network is widely distributed throughout a highly branched axonal arbor. Here we review the current understanding of the role of PINK1–Parkin in the quality control of mitophagy, including sensing of mitochondrial distress by PINK1, activation of Parkin by PINK1 to induce mitophagy, and the physiological relevance of the PINK1–Parkin pathway. Narendra and Youle review the current understanding of the role of PINK1–Parkin in the quality control of mitophagy, highlighting the underlying mechanisms and physiological relevance of the pathway, as well as its role in neuroprotection.","PeriodicalId":18977,"journal":{"name":"Nature Cell Biology","volume":"26 10","pages":"1639-1651"},"PeriodicalIF":17.3,"publicationDate":"2024-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142362787","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 : 2024-10-01DOI: 10.1038/s41556-024-01502-y
Ameya P. Jalihal, Zachary M. Geisterfer, Amy S. Gladfelter
The assembly of germ granules remains unknown, but recent attention to the role of RNA structure in membrane-less organelle assembly is changing our understanding of RNAs in the cell. Two studies now show how RNA–RNA interactions drive germ granule assembly and how germ granules spatially regulate embryonic mRNA translation.
{"title":"RNAs kiss and translate in germ granules","authors":"Ameya P. Jalihal, Zachary M. Geisterfer, Amy S. Gladfelter","doi":"10.1038/s41556-024-01502-y","DOIUrl":"10.1038/s41556-024-01502-y","url":null,"abstract":"The assembly of germ granules remains unknown, but recent attention to the role of RNA structure in membrane-less organelle assembly is changing our understanding of RNAs in the cell. Two studies now show how RNA–RNA interactions drive germ granule assembly and how germ granules spatially regulate embryonic mRNA translation.","PeriodicalId":18977,"journal":{"name":"Nature Cell Biology","volume":"26 11","pages":"1828-1829"},"PeriodicalIF":17.3,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142330376","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 : 2024-10-01DOI: 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
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. Zhao et al. report that the Z compartment protein HERD-1 regulates transgenerational epigenetic inheritance in Caenorhabditis elegans at least in part by preventing the mixing of germ granule condensates.
核仁、应激颗粒/加工体和胚芽颗粒等生物分子凝聚体是多相集合体，其形成机制和意义至今仍鲜为人知。在这里，我们利用优化的 TurboID 介导的近距离生物素标记，鉴定了草履虫胚芽颗粒中时空有序的 P、Z 和 M 多相凝聚体的蛋白质成分。其中包括 462、41 和 86 个分别定位到 P、Z 和 M 凝聚物的蛋白质，其中 522 个是以前未知的蛋白质成分。每种缩聚物的蛋白质都富含不同类别的结构域和内在无序域，这表明它们具有不同的功能和组装机制。通过功能筛选，我们发现了一种胚芽颗粒蛋白 HERD-1，它能阻止 P、Z 和 M 缩合物的混合。HERD-1突变体中的混合与种系小RNA通路的混乱和RNA干扰诱导的基因沉默的表观遗传时间延长有关。使用一种对绿色荧光蛋白具有特异性结合活性的纳米抗体强制混合这些凝聚物成分，也会延长表观遗传的时间。我们认为，积极维持胚芽颗粒的不溶性有助于组织和调节小 RNA 驱动的秀丽隐杆线虫转代表观遗传。
{"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":"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. Zhao et al. report that the Z compartment protein HERD-1 regulates transgenerational epigenetic inheritance in Caenorhabditis elegans at least in part by preventing the mixing of germ granule condensates.","PeriodicalId":18977,"journal":{"name":"Nature Cell Biology","volume":"26 11","pages":"1958-1970"},"PeriodicalIF":17.3,"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}
Pub Date : 2024-10-01DOI: 10.1038/s41556-024-01519-3
Mainak Bose, Branislava Rankovic, Julia Mahamid, Anne Ephrussi
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. Bose, Rankovic et al. show that a specific RNA–RNA kissing-loop interaction plays a crucial role in driving biomolecular condensation of ribonucleoprotein granules in the Drosophila germline.
{"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":"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. Bose, Rankovic et al. show that a specific RNA–RNA kissing-loop interaction plays a crucial role in driving biomolecular condensation of ribonucleoprotein granules in the Drosophila germline.","PeriodicalId":18977,"journal":{"name":"Nature Cell Biology","volume":"26 11","pages":"1934-1942"},"PeriodicalIF":17.3,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41556-024-01519-3.pdf","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":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-30DOI: 10.1038/s41556-024-01516-6
Livia Garzia
Circulating tumour cells from primary carcinomas may reach the brain and establish metastases. In the brain parenchyma, tumour cells initiate extensive interactions with resident astrocytes, microglia and neurons, forming a niche where tumour cells can thrive. A new study reveals a previously unknown type of astrocyte–tumour cell interaction.
{"title":"Astrocytes are enablers of brain metastases","authors":"Livia Garzia","doi":"10.1038/s41556-024-01516-6","DOIUrl":"10.1038/s41556-024-01516-6","url":null,"abstract":"Circulating tumour cells from primary carcinomas may reach the brain and establish metastases. In the brain parenchyma, tumour cells initiate extensive interactions with resident astrocytes, microglia and neurons, forming a niche where tumour cells can thrive. A new study reveals a previously unknown type of astrocyte–tumour cell interaction.","PeriodicalId":18977,"journal":{"name":"Nature Cell Biology","volume":"26 10","pages":"1632-1633"},"PeriodicalIF":17.3,"publicationDate":"2024-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142329656","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 : 2024-09-23DOI: 10.1038/s41556-024-01531-7
Shan Wang, Emelie Englund, Pontus Kjellman, Zhen Li, Johannes Kumra Ahnlide, Carmen Rodriguez-Cupello, Mattia Saggioro, Ryu Kanzaki, Kristian Pietras, David Lindgren, Håkan Axelson, Christelle N. Prinz, Vinay Swaminathan, Chris D. Madsen
{"title":"Retraction Note: CCM3 is a gatekeeper in focal adhesions regulating mechanotransduction and YAP/TAZ signalling","authors":"Shan Wang, Emelie Englund, Pontus Kjellman, Zhen Li, Johannes Kumra Ahnlide, Carmen Rodriguez-Cupello, Mattia Saggioro, Ryu Kanzaki, Kristian Pietras, David Lindgren, Håkan Axelson, Christelle N. Prinz, Vinay Swaminathan, Chris D. Madsen","doi":"10.1038/s41556-024-01531-7","DOIUrl":"10.1038/s41556-024-01531-7","url":null,"abstract":"","PeriodicalId":18977,"journal":{"name":"Nature Cell Biology","volume":"26 10","pages":"1817-1817"},"PeriodicalIF":17.3,"publicationDate":"2024-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41556-024-01531-7.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142308162","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}
Pub Date : 2024-09-20DOI: 10.1038/s41556-024-01510-y
During early mouse development, a fluid-filled lumen inflates the embryo. Membrane protrusions called inverse blebs have been found to form at cell–cell contacts. Cycles of inverse bleb filling and unloading act as hydraulic pumps and contribute to the formation of the lumen.
{"title":"Inverse bleb membrane protrusions pump fluid within the early mouse embryo","authors":"","doi":"10.1038/s41556-024-01510-y","DOIUrl":"10.1038/s41556-024-01510-y","url":null,"abstract":"During early mouse development, a fluid-filled lumen inflates the embryo. Membrane protrusions called inverse blebs have been found to form at cell–cell contacts. Cycles of inverse bleb filling and unloading act as hydraulic pumps and contribute to the formation of the lumen.","PeriodicalId":18977,"journal":{"name":"Nature Cell Biology","volume":"26 10","pages":"1637-1638"},"PeriodicalIF":17.3,"publicationDate":"2024-09-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142275149","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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