综合性期刊最新文献

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Root growth and branching are enabled by brassinosteroid-regulated growth anisotropy and carbon allocation 油菜素内酯调节的生长各向异性和碳分配促进了根的生长和分支
IF 16.6 1区 综合性期刊
Nature Communications Pub Date : 2025-04-28 DOI: 10.1038/s41467-025-59202-6
Hitaishi Khandal, Guy Horev, Bas van den Herik, Yoram Soroka, Tamar Lahav, Tamar Avin-Wittenberg, Kirsten ten Tusscher, Sigal Savaldi-Goldstein
{"title":"Root growth and branching are enabled by brassinosteroid-regulated growth anisotropy and carbon allocation","authors":"Hitaishi Khandal, Guy Horev, Bas van den Herik, Yoram Soroka, Tamar Lahav, Tamar Avin-Wittenberg, Kirsten ten Tusscher, Sigal Savaldi-Goldstein","doi":"10.1038/s41467-025-59202-6","DOIUrl":"https://doi.org/10.1038/s41467-025-59202-6","url":null,"abstract":"<p>Plants function as an integrated system of interconnected organs, with shoots and roots mutually influencing each other. Brassinosteroid (BR) signaling is essential for whole-plant growth, yet the relative importance of shoot versus root BR function in shaping root system architecture (RSA) remains unclear. Here, we directly tackle this question using micro-grafts between wild-type and BR-null mutants in both <i>Arabidopsis</i> and tomato, assisted by phenotyping, transcriptomics, metabolic profiling, transmission electron microscopy, and modeling approaches. These analyses demonstrate that shoot BR, by determining root carbon availability, allows for a full rescue of mutant root biomass, while loss of shoot BR attenuates root growth. In parallel, root BR dictates the spatial distribution of carbon along the root, through local regulation of growth anisotropy and cell wall thickness, shaping root morphology. A newly developed “grow and branch” simulation model demonstrates that these shoot- and root-derived BR effects are sufficient to explain and predict root growth dynamics and branching phenotype in wild-type, BR-deficient mutants, and micro-graft combinations. Our interdisciplinary approach, applied to two plant species and integrating shoot and root hormonal functions, provides a new understanding of how RSA is modulated at various scales.</p>","PeriodicalId":19066,"journal":{"name":"Nature Communications","volume":"83 1","pages":""},"PeriodicalIF":16.6,"publicationDate":"2025-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143884500","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Dissociation of SYNGAP1 enzymatic and structural roles: Intrinsic excitability and seizure susceptibility SYNGAP1酶解和结构作用:内在兴奋性和癫痫易感性
IF 11.1 1区 综合性期刊
Proceedings of the National Academy of Sciences of the United States of America Pub Date : 2025-04-28 DOI: 10.1073/pnas.2427288122
Julia Brill, Blaise Clarke, Ingie Hong, Richard L. Huganir
{"title":"Dissociation of SYNGAP1 enzymatic and structural roles: Intrinsic excitability and seizure susceptibility","authors":"Julia Brill, Blaise Clarke, Ingie Hong, Richard L. Huganir","doi":"10.1073/pnas.2427288122","DOIUrl":"https://doi.org/10.1073/pnas.2427288122","url":null,"abstract":"SYNGAP1 is a key Ras-GAP protein enriched at excitatory synapses, with mutations causing intellectual disability and epilepsy in humans. Recent studies have revealed that in addition to its role as a negative regulator of G-protein signaling through its GAP enzymatic activity, SYNGAP1 plays an important structural role through its interaction with postsynaptic density proteins. Here, we reveal that intrinsic excitability deficits and seizure phenotypes in heterozygous <jats:italic>Syngap1</jats:italic> knockout (KO) mice are differentially dependent on Syngap1 GAP activity. Cortical excitatory neurons in heterozygous KO mice displayed reduced intrinsic excitability, including lower input resistance, and increased rheobase, a phenotype recapitulated in GAP-deficient Syngap1 mutants. However, seizure severity and susceptibility to pentylenetetrazol (PTZ)-induced seizures were significantly elevated in heterozygous KO mice but unaffected in GAP-deficient mutants, implicating the structural rather than enzymatic role of Syngap1 in seizure regulation. These findings highlight the complex interplay between SYNGAP1 structural and catalytic functions in neuronal physiology and disease.","PeriodicalId":20548,"journal":{"name":"Proceedings of the National Academy of Sciences of the United States of America","volume":"10 1","pages":""},"PeriodicalIF":11.1,"publicationDate":"2025-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143884766","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Enantioselective dearomative ortho-cycloaddition transformation of unactivated arenes by cage-confined visible-light photocatalysis 笼型可见光催化非活化芳烃的对映选择性脱芳邻环加成转化
IF 16.6 1区 综合性期刊
Nature Communications Pub Date : 2025-04-28 DOI: 10.1038/s41467-025-59176-5
Jie Yang, Zhongshu Li, Xiantao Wu, Jie Chen, Sisi Huang, Yu-Lin Lu, Zhiwei Jiao, Cheng-Yong Su
{"title":"Enantioselective dearomative ortho-cycloaddition transformation of unactivated arenes by cage-confined visible-light photocatalysis","authors":"Jie Yang, Zhongshu Li, Xiantao Wu, Jie Chen, Sisi Huang, Yu-Lin Lu, Zhiwei Jiao, Cheng-Yong Su","doi":"10.1038/s41467-025-59176-5","DOIUrl":"https://doi.org/10.1038/s41467-025-59176-5","url":null,"abstract":"<p>Photoinduced dearomatization of arenes is a powerful strategy in organic synthesis to disrupt the stable aromaticity; however, the asymmetric dearomatization photocatalysis of unactivated arenes remains highly challenging and rare. Herein we demonstrate an enzyme-mimicking cage-confined visible-light asymmetric photocatalysis method for intramolecular dearomative cycloaddition with electron-deficient <i>β</i>-aryl enones. Owing to the multi-functional synergy of chirality, energy transfer, and host-guest interactions in the confined microenvironments, the self-assembled chiral cage-photoreactor could pre-organize the arenes and activate the <i>β</i>-aryl enones to give stereoselectively fused cyclobutanes through visible-light induced [2 + 2] <i>ortho</i>-cycloaddition. Notably, the competing transformation to stable [4 + 2] cycloadducts has been inhibited, producing thermodynamically unfavorable [2 + 2] cycloadducts with excellent regio-, diastereo-, and enantioselectivities.</p>","PeriodicalId":19066,"journal":{"name":"Nature Communications","volume":"43 1","pages":""},"PeriodicalIF":16.6,"publicationDate":"2025-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143884823","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Copy-cat evolution: Divergence and convergence within and between cat and dog breeds 模仿猫的进化:猫和狗品种内部和之间的分化和趋同
IF 11.1 1区 综合性期刊
Proceedings of the National Academy of Sciences of the United States of America Pub Date : 2025-04-28 DOI: 10.1073/pnas.2413780122
Abby Grace Drake, Liam J. Revell, Christian Peter Klingenberg, Jimmy C. Lattimer, Nathan C. Nelson, Martin J. Schmidt, Allison L. Zwingenberger, Joshua K. Moyer, Jonathan B. Losos
{"title":"Copy-cat evolution: Divergence and convergence within and between cat and dog breeds","authors":"Abby Grace Drake, Liam J. Revell, Christian Peter Klingenberg, Jimmy C. Lattimer, Nathan C. Nelson, Martin J. Schmidt, Allison L. Zwingenberger, Joshua K. Moyer, Jonathan B. Losos","doi":"10.1073/pnas.2413780122","DOIUrl":"https://doi.org/10.1073/pnas.2413780122","url":null,"abstract":"Many domesticated species exhibit remarkable phenotypic diversity. In nature, selection produces not only divergence but also convergence when organisms experience similar selective pressures. Whether artificial selection during domestication also produces convergence has received little attention. Three-dimensional shape analysis of domestic cat and dog skulls demonstrated convergence at multiple levels. Most broadly, cats and dogs have both diversified greatly: equaling or exceeding the morphological disparity among all modern-day species of their respective families. Moreover, as a result of artificial selection, some breeds of these two phenotypically distinct species, evolutionarily separated for 50 My, have converged to such an extreme extent that they are more similar to each other than they are to many members of their own species or their ancestors, a phenomenon never previously observed in domesticated species. Remarkably, this convergence evolved not only between dogs and cats but also multiple times within each taxon.","PeriodicalId":20548,"journal":{"name":"Proceedings of the National Academy of Sciences of the United States of America","volume":"8 1","pages":""},"PeriodicalIF":11.1,"publicationDate":"2025-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143884842","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Publisher Correction: irCLIP-RNP and Re-CLIP reveal patterns of dynamic protein assemblies on RNA 出版者更正:irCLIP-RNP和Re-CLIP揭示了RNA上动态蛋白质组装的模式
IF 64.8 1区 综合性期刊
Nature Pub Date : 2025-04-28 DOI: 10.1038/s41586-025-09055-2
Luca Ducoli, Brian J. Zarnegar, Douglas F. Porter, Robin M. Meyers, Weili Miao, Nicholas M. Riley, Suhas Srinivasan, Leandra V. Jackrazi, Yen-Yu Yang, Zhouxian Li, Yinsheng Wang, Carolyn R. Bertozzi, Ryan A. Flynn, Paul A. Khavari
{"title":"Publisher Correction: irCLIP-RNP and Re-CLIP reveal patterns of dynamic protein assemblies on RNA","authors":"Luca Ducoli, Brian J. Zarnegar, Douglas F. Porter, Robin M. Meyers, Weili Miao, Nicholas M. Riley, Suhas Srinivasan, Leandra V. Jackrazi, Yen-Yu Yang, Zhouxian Li, Yinsheng Wang, Carolyn R. Bertozzi, Ryan A. Flynn, Paul A. Khavari","doi":"10.1038/s41586-025-09055-2","DOIUrl":"https://doi.org/10.1038/s41586-025-09055-2","url":null,"abstract":"<p>Correction to: <i>Nature</i> https://doi.org/10.1038/s41586-025-08787-5 Published online 26 March 2025</p>","PeriodicalId":18787,"journal":{"name":"Nature","volume":"14 1","pages":""},"PeriodicalIF":64.8,"publicationDate":"2025-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143885018","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Dissecting cross-population polygenic heterogeneity across respiratory and cardiometabolic diseases 呼吸和心脏代谢疾病的跨人群多基因异质性剖析
IF 16.6 1区 综合性期刊
Nature Communications Pub Date : 2025-04-28 DOI: 10.1038/s41467-025-58149-y
Yuji Yamamoto, Yuya Shirai, Kyuto Sonehara, Shinichi Namba, Takafumi Ojima, Kenichi Yamamoto, Ryuya Edahiro, Ken Suzuki, Akinori Kanai, Yoshiya Oda, Yutaka Suzuki, Takayuki Morisaki, Akira Narita, Yoshito Takeda, Gen Tamiya, Masayuki Yamamoto, Koichi Matsuda, Atsushi Kumanogoh, Toshimasa Yamauchi, Takashi Kadowaki, Yukinori Okada
{"title":"Dissecting cross-population polygenic heterogeneity across respiratory and cardiometabolic diseases","authors":"Yuji Yamamoto, Yuya Shirai, Kyuto Sonehara, Shinichi Namba, Takafumi Ojima, Kenichi Yamamoto, Ryuya Edahiro, Ken Suzuki, Akinori Kanai, Yoshiya Oda, Yutaka Suzuki, Takayuki Morisaki, Akira Narita, Yoshito Takeda, Gen Tamiya, Masayuki Yamamoto, Koichi Matsuda, Atsushi Kumanogoh, Toshimasa Yamauchi, Takashi Kadowaki, Yukinori Okada","doi":"10.1038/s41467-025-58149-y","DOIUrl":"https://doi.org/10.1038/s41467-025-58149-y","url":null,"abstract":"<p>Biological mechanisms underlying multimorbidity remain elusive. To dissect the polygenic heterogeneity of multimorbidity in twelve complex traits across populations, we leveraged biobank resources of genome-wide association studies (GWAS) for 232,987 East Asian individuals (the 1st and 2nd cohorts of BioBank Japan) and 751,051 European individuals (UK Biobank and FinnGen). Cross-trait analyses of respiratory and cardiometabolic diseases, rheumatoid arthritis, and smoking identified negative genetic correlations between respiratory and cardiometabolic diseases in East Asian individuals, opposite from the positive associations in European individuals. Associating genome-wide polygenic risk scores (PRS) with 325 blood metabolome and 2917 proteome biomarkers supported the negative cross-trait genetic correlations in East Asian individuals. Bayesian pathway PRS analysis revealed a negative association between asthma and dyslipidemia in a gene set of peroxisome proliferator-activated receptors. The pathway suggested heterogeneity of cell type specificity in the enrichment analysis of the lung single-cell RNA-sequencing dataset. Our study highlights the heterogeneous pleiotropy of immunometabolic dysfunction in multimorbidity.</p>","PeriodicalId":19066,"journal":{"name":"Nature Communications","volume":"7 1","pages":""},"PeriodicalIF":16.6,"publicationDate":"2025-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143880497","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
PRPS2 enhances RNA m6A methylation by stimulating SAM synthesis through enzyme-dependent and independent mechanisms PRPS2通过酶依赖和独立的机制刺激SAM合成,从而增强RNA m6A甲基化
IF 16.6 1区 综合性期刊
Nature Communications Pub Date : 2025-04-28 DOI: 10.1038/s41467-025-59119-0
Lin Zhang, Xian Zhao, Jingyan Hu, Tingting Li, Hong-Zhuan Chen, Ao Zhang, Hao Wang, Jianxiu Yu, Liang Zhang
{"title":"PRPS2 enhances RNA m6A methylation by stimulating SAM synthesis through enzyme-dependent and independent mechanisms","authors":"Lin Zhang, Xian Zhao, Jingyan Hu, Tingting Li, Hong-Zhuan Chen, Ao Zhang, Hao Wang, Jianxiu Yu, Liang Zhang","doi":"10.1038/s41467-025-59119-0","DOIUrl":"https://doi.org/10.1038/s41467-025-59119-0","url":null,"abstract":"<p>Cancer cells exploit altered metabolic pathways to dynamically regulate epigenetic methylation and thus promote tumorigenesis and metastasis. In various human cancers, such as lung adenocarcinoma, the level of a key cellular metabolite, S-adenosylmethionine (SAM), is prominently upregulated for RNA hypermethylation as the methyl donor. However, the specific mechanisms by which cancer cells produce SAM to sustain RNA methylation remain elusive. Here, we demonstrate that PRPS2, a phosphoribosyl pyrophosphate synthetase isoform involved in the first and rate-limiting step of the purine biosynthesis pathway, exhibits distinct oncogenic functionality in regulating RNA methylation, unlike its homolog PRPS1. PRPS2 utilizes four non-conserved key residues to bypass the typical ADP/GDP allosteric feedback inhibition, enabling sustained excess production of newly synthesized ATP. Moreover, PRPS2 stabilizes methionine adenosyltransferase 2 A (MAT2A) through direct interactions to positively stimulate ATP utilization and SAM synthesis for RNA m<sup>6</sup>A specific methylation via the WTAP/METTL3/METTL14 methyltransferase complex, thereby promoting lung tumorigenesis. Our study links nucleotide biosynthesis with RNA epigenetics in cancer progression through the PRPS2-MAT2A-WTAP/METTL3/METTL14 axis, and elucidates both enzyme-dependent and independent functions of PRPS2. These findings have significant implications for developing targeted therapies for cancers associated with PRPS2 abnormalities.</p>","PeriodicalId":19066,"journal":{"name":"Nature Communications","volume":"17 1","pages":""},"PeriodicalIF":16.6,"publicationDate":"2025-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143880498","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Mass-independent fractionation of oxygen isotopes during high-temperature condensation in cosmochemical plasmas 宇宙化学等离子体高温凝聚过程中氧同位素的质量无关分馏
IF 11.1 1区 综合性期刊
Proceedings of the National Academy of Sciences of the United States of America Pub Date : 2025-04-28 DOI: 10.1073/pnas.2426711122
Nathan Asset, Marc Chaussidon, Guillaume Lombardi, Johan Villeneuve, Romain Tartèse, Smail Mostefaoui, François Robert
{"title":"Mass-independent fractionation of oxygen isotopes during high-temperature condensation in cosmochemical plasmas","authors":"Nathan Asset, Marc Chaussidon, Guillaume Lombardi, Johan Villeneuve, Romain Tartèse, Smail Mostefaoui, François Robert","doi":"10.1073/pnas.2426711122","DOIUrl":"https://doi.org/10.1073/pnas.2426711122","url":null,"abstract":"Contrary to all terrestrial rocks, planets and meteorites exhibit oxygen isotope variations decorrelated with the mass difference of their atomic nuclei. It has been proposed that, in the protosolar nebula (PSN), these variations could result from mass independent isotopic fractionation (MIF) either during specific chemical reactions similar to those responsible for the formation of ozone in the Earth’s atmosphere or during ultraviolet (UV)-photolysis of carbon monoxide (CO) gas in the PSN. However, these potential chemical MIF reactions (Chem-MIFs) are not identified in conditions close to the PSN, and there is no experimental demonstration that large MIF signature can be transferred to solids forming in the PSN. Here, we show that MIFs, up to 60‰ depletion in <jats:sup>16</jats:sup> O, are produced by high-temperature reactions in a plasma during the condensation of carbonaceous solids from a gas containing two of the most abundant PSN molecular species (H <jats:sub>2</jats:sub> O and CH <jats:sub>4</jats:sub> ). This effect is attributed to the formation in the plasma of the activated complex H <jats:sub>2</jats:sub> O <jats:sub>2</jats:sub> * followed by its stabilization by reactions with CH <jats:sub>x</jats:sub> <jats:sup>•</jats:sup> radicals. Although it is premature to assert that this reaction represents the main process resulting in MIF of oxygen isotopes in the solar system, our result demonstrates the potential importance of a Chem-MIF effect in a PSN where plasma zones develop.","PeriodicalId":20548,"journal":{"name":"Proceedings of the National Academy of Sciences of the United States of America","volume":"35 1","pages":""},"PeriodicalIF":11.1,"publicationDate":"2025-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143884838","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Structural basis for regulation of CELSR1 by a compact module in its extracellular region 胞外区域紧凑模块调控CELSR1的结构基础
IF 16.6 1区 综合性期刊
Nature Communications Pub Date : 2025-04-28 DOI: 10.1038/s41467-025-59319-8
Sumit J. Bandekar, Krassimira Garbett, Szymon P. Kordon, Ethan E. Dintzner, Jingxian Li, Tanner Shearer, Richard C. Sando, Demet Araç
{"title":"Structural basis for regulation of CELSR1 by a compact module in its extracellular region","authors":"Sumit J. Bandekar, Krassimira Garbett, Szymon P. Kordon, Ethan E. Dintzner, Jingxian Li, Tanner Shearer, Richard C. Sando, Demet Araç","doi":"10.1038/s41467-025-59319-8","DOIUrl":"https://doi.org/10.1038/s41467-025-59319-8","url":null,"abstract":"<p>The Cadherin EGF Laminin G seven-pass G-type receptor subfamily (CELSR/ADGRC) is one of the most conserved among adhesion G protein-coupled receptors and is essential for animal development. The extracellular regions (ECRs) of CELSRs are large with 23 adhesion domains. However, molecular insight into CELSR function is sparsely available. Here, we report the 3.8 Å cryo-EM reconstruction of the mouse CELSR1 ECR and reveal that 14 domains form a compact module mediated by conserved interactions majorly between the CADH9 and C-terminal GAIN domains. In the presence of Ca<sup>2+</sup>, the CELSR1 ECR forms a dimer species mediated by the cadherin repeats putatively in an antiparallel fashion. Cell-based assays reveal the N-terminal CADH1-8 repeat is required for cell-cell adhesion and the C-terminal CADH9-GAIN compact module can regulate cellular adhesion. Our work provides molecular insight into how one of the largest GPCRs uses defined structural modules to regulate receptor function.</p>","PeriodicalId":19066,"journal":{"name":"Nature Communications","volume":"14 1","pages":""},"PeriodicalIF":16.6,"publicationDate":"2025-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143880447","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
DNA damage in proximal tubules triggers systemic metabolic dysfunction through epigenetically altered macrophages 近端小管DNA损伤通过表观遗传改变巨噬细胞引发全身代谢功能障碍
IF 16.6 1区 综合性期刊
Nature Communications Pub Date : 2025-04-28 DOI: 10.1038/s41467-025-59297-x
Erina Sugita Nishimura, Akihito Hishikawa, Ran Nakamichi, Riki Akashio, Shunsuke Chikuma, Akinori Hashiguchi, Norifumi Yoshimoto, Eriko Yoshida Hama, Tomomi Maruki, Wataru Itoh, Shintaro Yamaguchi, Jun Yoshino, Hiroshi Itoh, Kaori Hayashi
{"title":"DNA damage in proximal tubules triggers systemic metabolic dysfunction through epigenetically altered macrophages","authors":"Erina Sugita Nishimura, Akihito Hishikawa, Ran Nakamichi, Riki Akashio, Shunsuke Chikuma, Akinori Hashiguchi, Norifumi Yoshimoto, Eriko Yoshida Hama, Tomomi Maruki, Wataru Itoh, Shintaro Yamaguchi, Jun Yoshino, Hiroshi Itoh, Kaori Hayashi","doi":"10.1038/s41467-025-59297-x","DOIUrl":"https://doi.org/10.1038/s41467-025-59297-x","url":null,"abstract":"<p>DNA damage repair is a critical physiological process closely linked to aging. The accumulation of DNA damage in renal proximal tubular epithelial cells (PTEC) is related to a decline in kidney function. Here, we report that DNA double-strand breaks in PTECs lead to systemic metabolic dysfunction, including weight loss, reduced fat mass, impaired glucose tolerance with mitochondrial dysfunction, and increased inflammation in adipose tissues and the liver. Single-cell RNA sequencing analysis reveals expansion of CD11c+ Ccr2+ macrophages in the kidney cortex, liver, and adipose tissues and Ly6C<sup>hi</sup> monocytes in peripheral blood. DNA damage in PTECs is associated with hypomethylation of macrophage activation genes, including Gasdermin D, in peripheral blood cells, which is linked to reduced DNA methylation at KLF9-binding motifs. Macrophage depletion ameliorates metabolic abnormalities. These findings highlight the impact of kidney DNA damage on systemic metabolic homeostasis, revealing a kidney-blood-metabolism axis mediated by epigenetic changes in macrophages.</p>","PeriodicalId":19066,"journal":{"name":"Nature Communications","volume":"17 1","pages":""},"PeriodicalIF":16.6,"publicationDate":"2025-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143880495","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
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