Nature Cell Biology最新文献

{"title":"FMRP regulates MFF translation to locally direct mitochondrial fission in neurons","authors":"Adam R. Fenton, Ruchao Peng, Charles Bond, Siewert Hugelier, Melike Lakadamyali, Yi-Wei Chang, Erika L. F. Holzbaur, Thomas A. Jongens","doi":"10.1038/s41556-024-01544-2","DOIUrl":"10.1038/s41556-024-01544-2","url":null,"abstract":"Fragile X messenger ribonucleoprotein (FMRP) is a critical regulator of translation, whose dysfunction causes fragile X syndrome. FMRP dysfunction disrupts mitochondrial health in neurons, but it is unclear how FMRP supports mitochondrial homoeostasis. Here we demonstrate that FMRP granules are recruited to the mitochondrial midzone, where they mark mitochondrial fission sites in axons and dendrites. Endolysosomal vesicles contribute to FMRP granule positioning around mitochondria and facilitate FMRP-associated fission via Rab7 GTP hydrolysis. Cryo-electron tomography and real-time translation imaging reveal that mitochondria-associated FMRP granules are ribosome-rich structures that serve as sites of local protein synthesis. Specifically, FMRP promotes local translation of mitochondrial fission factor (MFF), selectively enabling replicative fission at the mitochondrial midzone. Disrupting FMRP function dysregulates mitochondria-associated MFF translation and perturbs fission dynamics, resulting in increased peripheral fission and an irregular distribution of mitochondrial nucleoids. Thus, FMRP regulates local translation of MFF in neurons, enabling precise control of mitochondrial fission. Fenton et al. show that FMRP granules dock at the mitochondrial midzone in a Rab7-dependent manner in axons and dendrites, where they promote local MFF synthesis and fission at the mitochondrial midzone.","PeriodicalId":18977,"journal":{"name":"Nature Cell Biology","volume":"26 12","pages":"2061-2074"},"PeriodicalIF":17.3,"publicationDate":"2024-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41556-024-01544-2.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142637052","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}

{"title":"Chromatin remodelling in damaged intestinal crypts orchestrates redundant TGFβ and Hippo signalling to drive regeneration","authors":"Mardi Fink, Kizito Njah, Shyam J. Patel, David P. Cook, Vanessa Man, Francesco Ruso, Arsheen Rajan, Masahiro Narimatsu, Andreea Obersterescu, Melanie J. Pye, Daniel Trcka, Kin Chan, Arshad Ayyaz, Jeffrey L. Wrana","doi":"10.1038/s41556-024-01550-4","DOIUrl":"10.1038/s41556-024-01550-4","url":null,"abstract":"Cell state dynamics underlying successful tissue regeneration are undercharacterized. In the intestine, damage prompts epithelial reprogramming into revival stem cells (revSCs) that reconstitute Lgr5+ intestinal stem cells (ISCs). Here single-nuclear multi-omics of mouse crypts regenerating from irradiation shows revSC chromatin accessibility overlaps with ISCs and differentiated lineages. While revSC genes themselves are accessible throughout homeostatic epithelia, damage-induced remodelling of chromatin in the crypt converges on Hippo and the transforming growth factor-beta (TGFβ) signalling pathway, which we show is transiently activated and directly induces functional revSCs. Combinatorial gene expression analysis further suggests multiple sources of revSCs, and we demonstrate TGFβ can reprogramme enterocytes, goblet and paneth cells into revSCs and show individual revSCs form organoids. Despite this, loss of TGFβ signalling yields mild regenerative defects, whereas interference in both Hippo and TGFβ leads to profound defects and death. Intestinal regeneration is thus poised for activation by a compensatory system of crypt-localized, transient morphogen cues that support epithelial reprogramming and robust intestinal repair. Using deep single-nucleus multi-omics profiling, Fink et al. report transition states between crypt epithelial cells and a revival stem cell lineage. They find that the TGFβ and Hippo signalling pathways cooperatively drive intestinal regeneration.","PeriodicalId":18977,"journal":{"name":"Nature Cell Biology","volume":"26 12","pages":"2084-2098"},"PeriodicalIF":17.3,"publicationDate":"2024-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142637051","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}

{"title":"A systemic effect for liver senescence","authors":"Kuo Du, David Scott Umbaugh, Rajesh Kumar Dutta, Anna Mae Diehl","doi":"10.1038/s41556-024-01520-w","DOIUrl":"10.1038/s41556-024-01520-w","url":null,"abstract":"A study shows that senescence induced in the liver can spread systemically to precipitate multi-organ dysfunction. The work identifies TGFβ signalling as a key mediator of this transmission, suggesting therapeutic avenues to prevent multi-organ failure in severe liver diseases.","PeriodicalId":18977,"journal":{"name":"Nature Cell Biology","volume":"26 12","pages":"2016-2017"},"PeriodicalIF":17.3,"publicationDate":"2024-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142601021","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}

{"title":"Hepatocellular senescence induces multi-organ senescence and dysfunction via TGFβ","authors":"Christos Kiourtis, Maria Terradas-Terradas, Lucy M. Gee, Stephanie May, Anastasia Georgakopoulou, Amy L. Collins, Eoin D. O’Sullivan, David P. Baird, Mohsin Hassan, Robin Shaw, Ee Hong Tan, Miryam Müller, Cornelius Engelmann, Fausto Andreola, Ya-Ching Hsieh, Lee H. Reed, Lee A. Borthwick, Colin Nixon, William Clark, Peter S. Hanson, David Sumpton, Gillian Mackay, Toshiyasu Suzuki, Arafath K. Najumudeen, Gareth J. Inman, Andrew Campbell, Simon T. Barry, Alberto Quaglia, Christopher M. Morris, Fiona E. N. LeBeau, Owen J. Sansom, Kristina Kirschner, Rajiv Jalan, Fiona Oakley, Thomas G. Bird","doi":"10.1038/s41556-024-01543-3","DOIUrl":"10.1038/s41556-024-01543-3","url":null,"abstract":"Cellular senescence is not only associated with ageing but also impacts physiological and pathological processes, such as embryonic development and wound healing. Factors secreted by senescent cells affect their microenvironment and can induce spreading of senescence locally. Acute severe liver disease is associated with hepatocyte senescence and frequently progresses to multi-organ failure. Why the latter occurs is poorly understood. Here we demonstrate senescence development in extrahepatic organs and associated organ dysfunction in response to liver senescence using liver injury models and genetic models of hepatocyte-specific senescence. In patients with severe acute liver failure, we show that the extent of hepatocellular senescence predicts disease outcome, the need for liver transplantation and the occurrence of extrahepatic organ failure. We identify the TGFβ pathway as a critical mediator of systemic spread of senescence and demonstrate that TGFβ inhibition in vivo blocks senescence transmission to other organs, preventing liver senescence induced renal dysfunction. Our results highlight the systemic consequences of organ-specific senescence, which, independent of ageing, contributes to multi-organ dysfunction. Kiourtis et al. show that liver senescence triggers senescence and dysfunction in other organs through TGFβ secretion from the liver.","PeriodicalId":18977,"journal":{"name":"Nature Cell Biology","volume":"26 12","pages":"2075-2083"},"PeriodicalIF":17.3,"publicationDate":"2024-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41556-024-01543-3.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142601023","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}

{"title":"Lipid droplet messengers","authors":"Melina Casadio","doi":"10.1038/s41556-024-01563-z","DOIUrl":"10.1038/s41556-024-01563-z","url":null,"abstract":"","PeriodicalId":18977,"journal":{"name":"Nature Cell Biology","volume":"26 11","pages":"1825-1825"},"PeriodicalIF":17.3,"publicationDate":"2024-11-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142599619","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}

{"title":"Cyclic mRNA localization in P-bodies","authors":"Sabrya Carim","doi":"10.1038/s41556-024-01561-1","DOIUrl":"10.1038/s41556-024-01561-1","url":null,"abstract":"","PeriodicalId":18977,"journal":{"name":"Nature Cell Biology","volume":"26 11","pages":"1825-1825"},"PeriodicalIF":17.3,"publicationDate":"2024-11-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142599620","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}

{"title":"To eat or not to eat","authors":"Stylianos Lefkopoulos","doi":"10.1038/s41556-024-01560-2","DOIUrl":"10.1038/s41556-024-01560-2","url":null,"abstract":"","PeriodicalId":18977,"journal":{"name":"Nature Cell Biology","volume":"26 11","pages":"1825-1825"},"PeriodicalIF":17.3,"publicationDate":"2024-11-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142599618","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}

{"title":"Specialized post-arterial capillaries facilitate adult bone remodelling","authors":"Vishal Mohanakrishnan, Kishor K. Sivaraj, Hyun-Woo Jeong, Esther Bovay, Backialakshmi Dharmalingam, M. Gabriele Bixel, Van Vuong Dinh, Milena Petkova, Isidora Paredes Ugarte, Yi-Tong Kuo, Malarvizhi Gurusamy, Brian Raftrey, Nelson Tsz Long Chu, Soumyashree Das, Pamela E. Rios Coronado, Martin Stehling, Lars Sävendahl, Andrei S. Chagin, Taija Mäkinen, Kristy Red-Horse, Ralf H. Adams","doi":"10.1038/s41556-024-01545-1","DOIUrl":"10.1038/s41556-024-01545-1","url":null,"abstract":"The vasculature of the skeletal system is crucial for bone formation, homoeostasis and fracture repair, yet the diversity and specialization of bone-associated vessels remain poorly understood. Here we identify a specialized type of post-arterial capillary, termed type R, involved in bone remodelling. Type R capillaries emerge during adolescence around trabecular bone, possess a distinct morphology and molecular profile, and are associated with osteoprogenitors and bone-resorbing osteoclasts. Endothelial cell-specific overexpression of the transcription factor DACH1 in postnatal mice induces a strong increase in arteries and type R capillaries, leading to local metabolic changes and enabling trabecular bone formation in normally highly hypoxic areas of the diaphysis. Indicating potential clinical relevance of type R capillaries, these vessels respond to anti-osteoporosis treatments and emerge during ageing inside porous structures that are known to weaken compact bone. Our work outlines fundamental principles of vessel specialization in the developing, adult and ageing skeletal system. Mohanakrishnan et al. identify a distinct subset of post-arterial capillaries, termed type R. They show that type R capillaries contribute to trabecular bone formation in the diaphysis and respond to anti-osteoporosis treatments.","PeriodicalId":18977,"journal":{"name":"Nature Cell Biology","volume":"26 12","pages":"2020-2034"},"PeriodicalIF":17.3,"publicationDate":"2024-11-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41556-024-01545-1.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142598342","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}

{"title":"Seeing tension in cells","authors":"Daryl J. V. David","doi":"10.1038/s41556-024-01562-0","DOIUrl":"10.1038/s41556-024-01562-0","url":null,"abstract":"","PeriodicalId":18977,"journal":{"name":"Nature Cell Biology","volume":"26 11","pages":"1825-1825"},"PeriodicalIF":17.3,"publicationDate":"2024-11-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142599617","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}

{"title":"Navigating human embryogenesis through tailored model selection","authors":"Berna Sozen","doi":"10.1038/s41556-024-01525-5","DOIUrl":"10.1038/s41556-024-01525-5","url":null,"abstract":"Rapid advances in stem cell and bioengineering technologies have sparked a revolution in developmental biology, with stem cell-based embryo models emerging as crucial tools to uncover the intricacies of human embryogenesis. However, making progress relies on precisely posing our questions and selecting our models.","PeriodicalId":18977,"journal":{"name":"Nature Cell Biology","volume":"26 11","pages":"1819-1821"},"PeriodicalIF":17.3,"publicationDate":"2024-11-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142599621","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}