EMBO Reports最新文献_第4页

Novel integrated multiomics analysis reveals a key role for integrin beta-like 1 in wound scarring. 新颖的多组学综合分析揭示了整合素 beta 样 1 在伤口瘢痕形成中的关键作用。

IF 6.5 1区生物学

EMBO Reports Pub Date : 2025-01-01 Epub Date: 2024-11-18 DOI: 10.1038/s44319-024-00322-3

Sang-Eun Kim, Ryota Noda, Yu-Chen Liu, Yukari Nakajima, Shoichiro Kameoka, Daisuke Motooka, Seiya Mizuno, Satoru Takahashi, Kento Takaya, Takehiko Murase, Kazuya Ikematsu, Katsiaryna Tratsiakova, Takahiro Motoyama, Masahiro Nakashima, Kazuo Kishi, Paul Martin, Shigeto Seno, Daisuke Okuzaki, Ryoichi Mori

{"title":"Novel integrated multiomics analysis reveals a key role for integrin beta-like 1 in wound scarring.","authors":"Sang-Eun Kim, Ryota Noda, Yu-Chen Liu, Yukari Nakajima, Shoichiro Kameoka, Daisuke Motooka, Seiya Mizuno, Satoru Takahashi, Kento Takaya, Takehiko Murase, Kazuya Ikematsu, Katsiaryna Tratsiakova, Takahiro Motoyama, Masahiro Nakashima, Kazuo Kishi, Paul Martin, Shigeto Seno, Daisuke Okuzaki, Ryoichi Mori","doi":"10.1038/s44319-024-00322-3","DOIUrl":"10.1038/s44319-024-00322-3","url":null,"abstract":"Exacerbation of scarring can originate from a minority fibroblast population that has undergone inflammatory-mediated genetic changes within the wound microenvironment. The fundamental relationship between molecular and spatial organization of the repair process at the single-cell level remains unclear. We have developed a novel, high-resolution spatial multiomics method that integrates spatial transcriptomics with scRNA-Seq; we identified new characteristic features of cell-cell communication and signaling during the repair process. Data from PU.1-/- mice, which lack an inflammatory response, combined with scRNA-Seq and Visium transcriptomics, led to the identification of nine genes potentially involved in inflammation-related scarring, including integrin beta-like 1 (Itgbl1). Transgenic mouse experiments confirmed that Itgbl1-expressing fibroblasts are required for granulation tissue formation and drive fibrogenesis during skin repair. Additionally, we detected a minority population of Acta2high-expressing myofibroblasts with apparent involvement in scarring, in conjunction with Itgbl1 expression. IL1β signaling inhibited Itgbl1 expression in TGFβ1-treated primary fibroblasts from humans and mice. Our novel methodology reveal molecular mechanisms underlying fibroblast-inflammatory cell interactions that initiate wound scarring.","PeriodicalId":11541,"journal":{"name":"EMBO Reports","volume":" ","pages":"122-152"},"PeriodicalIF":6.5,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11724056/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142667120","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

Heterochromatin-dependent transcription links the PRC2 complex to small RNA-mediated DNA elimination. 异染色质依赖性转录将PRC2复合体与小rna介导的DNA消除联系起来。

IF 6.5 1区生物学

EMBO Reports Pub Date : 2025-01-01 Epub Date: 2024-11-29 DOI: 10.1038/s44319-024-00332-1

Therese Solberg, Chundi Wang, Ryuma Matsubara, Zhiwei Wen, Mariusz Nowacki

{"title":"Heterochromatin-dependent transcription links the PRC2 complex to small RNA-mediated DNA elimination.","authors":"Therese Solberg, Chundi Wang, Ryuma Matsubara, Zhiwei Wen, Mariusz Nowacki","doi":"10.1038/s44319-024-00332-1","DOIUrl":"10.1038/s44319-024-00332-1","url":null,"abstract":"Facultative heterochromatin is marked by the repressive histone modification H3K27me3 in eukaryotes. Deposited by the PRC2 complex, H3K27me3 is essential for regulating gene expression during development, and chromatin bearing this mark is generally considered transcriptionally inert. The PRC2 complex has also been linked to programmed DNA elimination during development in ciliates such as Paramecium. Due to a lack of mechanistic insight, a direct involvement has been questioned as most eliminated DNA segments in Paramecium are shorter than the size of a nucleosome. Here, we identify two sets of histone methylation readers essential for PRC2-mediated DNA elimination in Paramecium: Firefly1/2 and Mayfly1-4. The chromodomain proteins Firefly1/2 act in tight association with TFIIS4, a transcription elongation factor required for noncoding RNA transcription. These noncoding transcripts act as scaffolds for sequence-specific targeting by PIWI-bound sRNAs, resulting in local nucleosome depletion and DNA elimination. Our findings elucidate the molecular mechanism underlying the role of PRC2 in PIWI-mediated DNA elimination and suggest that its role in IES elimination may be to activate rather than repress transcription.","PeriodicalId":11541,"journal":{"name":"EMBO Reports","volume":" ","pages":"273-296"},"PeriodicalIF":6.5,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11723920/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142754794","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

KMT5C leverages disorder to optimize cooperation with HP1 for heterochromatin retention. KMT5C 利用紊乱来优化与 HP1 的合作，以保持异染色质。

IF 6.5 1区生物学

EMBO Reports Pub Date : 2025-01-01 Epub Date: 2024-11-19 DOI: 10.1038/s44319-024-00320-5

Justin W Knechtel, Hilmar Strickfaden, Kristal Missiaen, Joanne D Hadfield, Michael J Hendzel, D Alan Underhill

{"title":"KMT5C leverages disorder to optimize cooperation with HP1 for heterochromatin retention.","authors":"Justin W Knechtel, Hilmar Strickfaden, Kristal Missiaen, Joanne D Hadfield, Michael J Hendzel, D Alan Underhill","doi":"10.1038/s44319-024-00320-5","DOIUrl":"10.1038/s44319-024-00320-5","url":null,"abstract":"A defining feature of constitutive heterochromatin compartments is the heterochromatin protein-1 (HP1) family, whose members display fast internal mobility and rapid exchange with the surrounding nucleoplasm. Here, we describe a paradoxical state for the lysine methyltransferase KMT5C characterized by rapid internal diffusion but minimal nucleoplasmic exchange. This retentive behavior is conferred by sparse sequence features that constitute two modules tethered by an intrinsically disordered linker. While both modules harbor variant HP1 interaction motifs, the first comprises adjacent sequences that increase affinity using avidity. The second motif increases HP1 effective concentration to further enhance affinity in a context-dependent manner, which is evident using distinct heterochromatin recruitment strategies and heterologous linkers with defined conformational ensembles. Despite the linker sequence being highly divergent, it is under evolutionary constraint for functional length, suggesting conformational buffering can support cooperativity between modules across distant orthologs. Overall, we show that KMT5C has evolved a robust tethering strategy that uses minimal sequence determinants to harness highly dynamic HP1 proteins for retention within heterochromatin compartments.","PeriodicalId":11541,"journal":{"name":"EMBO Reports","volume":" ","pages":"153-174"},"PeriodicalIF":6.5,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11723951/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142675462","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

The TGF-β mimic TGM4 achieves cell specificity through combinatorial surface co-receptor binding. TGF-β模拟物TGM4通过组合表面共受体结合实现细胞特异性。

IF 6.5 1区生物学

EMBO Reports Pub Date : 2025-01-01 Epub Date: 2024-11-28 DOI: 10.1038/s44319-024-00323-2

Shashi P Singh, Danielle J Smyth, Kyle T Cunningham, Ananya Mukundan, Chang-Hyeock Byeon, Cynthia S Hinck, Madeleine P J White, Claire Ciancia, Natalia Wąsowska, Anna Sanders, Regina Jin, Ruby F White, Sergio Lilla, Sara Zanivan, Christina Schoenherr, Gareth J Inman, Maarten van Dinther, Peter Ten Dijke, Andrew P Hinck, Rick M Maizels

{"title":"The TGF-β mimic TGM4 achieves cell specificity through combinatorial surface co-receptor binding.","authors":"Shashi P Singh, Danielle J Smyth, Kyle T Cunningham, Ananya Mukundan, Chang-Hyeock Byeon, Cynthia S Hinck, Madeleine P J White, Claire Ciancia, Natalia Wąsowska, Anna Sanders, Regina Jin, Ruby F White, Sergio Lilla, Sara Zanivan, Christina Schoenherr, Gareth J Inman, Maarten van Dinther, Peter Ten Dijke, Andrew P Hinck, Rick M Maizels","doi":"10.1038/s44319-024-00323-2","DOIUrl":"10.1038/s44319-024-00323-2","url":null,"abstract":"The immunoregulatory cytokine TGF-β is pleiotropic due to the near-ubiquitous expression of the TGF-β receptors TβRI and TβRII on diverse cell types. The helminth parasite Heligmosomoides polygyrus has convergently evolved a family of TGF-β mimics (TGMs) that bind both these receptors through domains 1-3 of a 5-domain protein. One member of this family, TGM4, differs from TGF-β in acting in a cell-specific manner, failing to stimulate fibroblasts, but activating SMAD phosphorylation in macrophages. Primarily through domains 4 and 5, TGM4 interacts with multiple co-receptors, including CD44, CD49d (integrin α4) and CD206, and can up- and downmodulate macrophage responses to IL-4 and lipopolysaccharide (LPS), respectively. The dependence of TGM4 on combinatorial interactions with co-receptors is due to a moderated affinity for TβRII that is more than 100-fold lower than for TGF-β. Thus the parasite has elaborated TGF-β receptor interactions to establish cell specificity through combinatorial cis-signalling, an innovation absent from the mammalian cytokine.","PeriodicalId":11541,"journal":{"name":"EMBO Reports","volume":" ","pages":"218-244"},"PeriodicalIF":6.5,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11723922/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142750492","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

The TRIM37 variant rs57141087 contributes to triple-negative breast cancer outcomes in Black women. TRIM37变体rs57141087与黑人女性的三阴性乳腺癌结局有关。

IF 6.5 1区生物学

EMBO Reports Pub Date : 2025-01-01 Epub Date: 2024-11-29 DOI: 10.1038/s44319-024-00331-2

Rachisan Djiake Tihagam, Song Lou, Yuanji Zhao, Kammi Song-Yan Liu, Arjun Tushir Singh, Bon Il Koo, Piotr Przanowski, Jie Li, Xiaosong Huang, Hong Li, Jogender Tushir-Singh, Laura Fejerman, Sanchita Bhatnagar

{"title":"The TRIM37 variant rs57141087 contributes to triple-negative breast cancer outcomes in Black women.","authors":"Rachisan Djiake Tihagam, Song Lou, Yuanji Zhao, Kammi Song-Yan Liu, Arjun Tushir Singh, Bon Il Koo, Piotr Przanowski, Jie Li, Xiaosong Huang, Hong Li, Jogender Tushir-Singh, Laura Fejerman, Sanchita Bhatnagar","doi":"10.1038/s44319-024-00331-2","DOIUrl":"10.1038/s44319-024-00331-2","url":null,"abstract":"Triple-negative breast cancer (TNBC) disproportionately affects younger Black women, who show more aggressive phenotypes and poorer outcomes than women of other racial identities. While the impact of socioenvironmental inequities within and beyond health systems is well documented, the genetic influence in TNBC-associated racial disparities remains elusive. Here, we report that cancer-free breast tissue from Black women expresses TRIM37 at a significantly higher level relative to White women. A reporter-based screen for regulatory variants identifies a non-coding risk variant rs57141087 in the 5' gene upstream region of the TRIM37 locus with enhancer activity. Mechanistically, rs57141087 increases enhancer-promoter interactions through NRF1, resulting in stronger TRIM37 promoter activity. Phenotypically, high TRIM37 levels drive neoplastic transformations in immortalized breast epithelial cells. Finally, context-dependent TRIM37 expression reveals that early-stage TRIM37 levels affect the initiation and trajectory of breast cancer progression. Together, our results indicate a genotype-informed association of oncogenic TRIM37 with TNBC risk in Black women and implicate TRIM37 as a predictive biomarker to better identify patients at risk of aggressive TNBC.","PeriodicalId":11541,"journal":{"name":"EMBO Reports","volume":" ","pages":"245-272"},"PeriodicalIF":6.5,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11723928/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142754796","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

Interleukin-2-mediated NF-κB-dependent mRNA splicing modulates interferon gamma protein production. 白细胞介素-2 介导的 NF-κB 依赖性 mRNA 剪接调节干扰素γ 蛋白的产生。

IF 6.5 1区生物学

EMBO Reports Pub Date : 2025-01-01 Epub Date: 2024-11-22 DOI: 10.1038/s44319-024-00324-1

Rachel D Van Gelder, Nandan S Gokhale, Emmanuelle Genoyer, Dylan S Omelia, Stephen K Anderson, Howard A Young, Ram Savan

{"title":"Interleukin-2-mediated NF-κB-dependent mRNA splicing modulates interferon gamma protein production.","authors":"Rachel D Van Gelder, Nandan S Gokhale, Emmanuelle Genoyer, Dylan S Omelia, Stephen K Anderson, Howard A Young, Ram Savan","doi":"10.1038/s44319-024-00324-1","DOIUrl":"10.1038/s44319-024-00324-1","url":null,"abstract":"Interferon-gamma (IFNγ) is a pleiotropic cytokine produced by natural killer (NK) cells during the early infection response. IFNγ expression is tightly regulated to mount sterilizing immunity while preventing tissue pathology. Several post-transcriptional effectors dampen IFNγ expression through IFNG mRNA degradation. In this study, we identify mRNA splicing as a positive regulator of IFNγ production. While treatment with the combination of IL-12 and IL-2 causes synergistic induction of IFNG mRNA and protein, defying transcription-translation kinetics, we observe that NK cells treated with IL-12 alone transcribe IFNG with introns intact. When NK cells are treated with both IL-2 and IL-12, IFNG transcript is spliced to form mature mRNA with a concomitant increase in IFNγ protein. We find that IL-2-mediated intron splicing occurs independently of nascent transcription but relies upon NF-κB signaling. We propose that while IL-12 transcriptionally induces IFNG mRNA, IL-2 signaling stabilizes IFNG mRNA by splicing detained introns, allowing for rapid IFNγ protein production. This study uncovers a novel role for cytokine-induced splicing in regulating IFNγ through a mechanism potentially applicable to other inflammatory mediators.","PeriodicalId":11541,"journal":{"name":"EMBO Reports","volume":" ","pages":"16-35"},"PeriodicalIF":6.5,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11724048/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142692807","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

The history of GM crops in Italy : After two decades of a de facto ban, the engagement of farmers and scientists has prompted the Italian government to allow field-testing of NGT/TEA plants again. 转基因作物在意大利的历史：经过二十年的实际禁令，农民和科学家的参与促使意大利政府再次允许对 NGT/TEA 植物进行田间试验。

IF 6.5 1区生物学

EMBO Reports Pub Date : 2025-01-01 Epub Date: 2024-11-27 DOI: 10.1038/s44319-024-00330-3

Roberto Defez, Maria Chiara Errigo, Giulia Formici, Lucia Scaffardi, Eleonora Sirsi, Fabio Fornara, Vittoria Brambilla

引用次数: 0

Palmitoylation by ZDHHC4 inhibits TRPV1-mediated nociception. ZDHHC4 的棕榈酰化抑制了 TRPV1 介导的痛觉。

IF 6.5 1区生物学

EMBO Reports Pub Date : 2025-01-01 Epub Date: 2024-11-11 DOI: 10.1038/s44319-024-00317-0

Youjing Zhang, Mengyu Zhang, Cheng Tang, Junyan Hu, Xufeng Cheng, Yang Li, Zefeng Chen, Yuan Yin, Chang Xie, Dongdong Li, Jing Yao

引用次数: 0

The DNA demethylase TET1 modifies the impact of maternal folic acid status on embryonic brain development. DNA 去甲基化酶 TET1 可改变母体叶酸状况对胚胎大脑发育的影响。

IF 6.5 1区生物学

EMBO Reports Pub Date : 2025-01-01 Epub Date: 2024-11-22 DOI: 10.1038/s44319-024-00316-1

Lehua Chen, Bernard K van der Veer, Qiuying Chen, Spyridon Champeris Tsaniras, Wannes Brangers, Harm H M Kwak, Rita Khoueiry, Yunping Lei, Robert Cabrera, Steven S Gross, Richard H Finnell, Kian Peng Koh

{"title":"The DNA demethylase TET1 modifies the impact of maternal folic acid status on embryonic brain development.","authors":"Lehua Chen, Bernard K van der Veer, Qiuying Chen, Spyridon Champeris Tsaniras, Wannes Brangers, Harm H M Kwak, Rita Khoueiry, Yunping Lei, Robert Cabrera, Steven S Gross, Richard H Finnell, Kian Peng Koh","doi":"10.1038/s44319-024-00316-1","DOIUrl":"10.1038/s44319-024-00316-1","url":null,"abstract":"Folic acid (FA) is well known to prevent neural tube defects (NTDs), but we do not know why many human NTD cases still remain refractory to FA supplementation. Here, we investigate how the DNA demethylase TET1 interacts with maternal FA status to regulate mouse embryonic brain development. We determined that cranial NTDs display higher penetrance in non-inbred than in inbred Tet1-/- embryos and are resistant to FA supplementation across strains. Maternal diets that are either too rich or deficient in FA are linked to an increased incidence of cranial deformities in wild type and Tet1+/- offspring and to altered DNA hypermethylation in Tet1-/- embryos, primarily at neurodevelopmental loci. Excess FA in Tet1-/- embryos results in phospholipid metabolite loss and reduced expression of multiple membrane solute carriers, including a FA transporter gene that exhibits increased promoter DNA methylation and thereby mimics FA deficiency. Moreover, FA deficiency reveals that Tet1 haploinsufficiency can contribute to DNA hypermethylation and susceptibility to NTDs. Overall, our study suggests that epigenetic dysregulation may underlie NTD development despite FA supplementation.","PeriodicalId":11541,"journal":{"name":"EMBO Reports","volume":" ","pages":"175-199"},"PeriodicalIF":6.5,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11724065/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142692809","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

Can bacteria think? 细菌会思考吗？

IF 6.5 1区生物学

EMBO Reports Pub Date : 2025-01-01 Epub Date: 2024-11-25 DOI: 10.1038/s44319-024-00334-z

Howy Jacobs

引用次数: 0