Communications Biology最新文献_第10页

Visualizing the human olfactory projection and ancillary structures in a 3D reconstruction. 在三维重建中可视化人类嗅觉投影和附属结构。

IF 5.2 1区生物学

Communications Biology Pub Date : 2024-11-08 DOI: 10.1038/s42003-024-07017-4

Victoria F Low, Chinchien Lin, Shan Su, Mahyar Osanlouy, Mona Khan, Soroush Safaei, Gonzalo Maso Talou, Maurice A Curtis, Peter Mombaerts

{"title":"Visualizing the human olfactory projection and ancillary structures in a 3D reconstruction.","authors":"Victoria F Low, Chinchien Lin, Shan Su, Mahyar Osanlouy, Mona Khan, Soroush Safaei, Gonzalo Maso Talou, Maurice A Curtis, Peter Mombaerts","doi":"10.1038/s42003-024-07017-4","DOIUrl":"10.1038/s42003-024-07017-4","url":null,"abstract":"Visualizing in 3D the histological microanatomy of the human olfactory projection from the olfactory mucosa in the nasal cavity to the olfactory bulbs in the cranial cavity necessitates a workflow for handling a great many sections. Here, we assembled a 3D reconstruction of a 7.45 cm3 en-bloc specimen extracted from an embalmed human cadaver. A series of 10 µm coronal sections was stained with quadruple fluorescence histology and scanned in four channels. A trained anatomist manually segmented six structures of interest in a subset of the sections to generate the ground truth. Six convolutional neural networks were then trained for automatic segmentation of these structures in 1234 sections. A high-performance computing solution was engineered to register the sections based on the fluorescence signal and segmented structures. The resulting 3D visualization offers several novel didactic opportunities of interactive exploration and virtual manipulation. By extrapolating manual counts of OSNs in a subset of sections to the calculated volume of the envelope of the entire olfactory epithelium, we computed a total of ~2.7 million OSNs in the specimen. Such empirically derived information helps assess the extent to which the organizational principles of the human olfactory projection may differ from those in mice.","PeriodicalId":10552,"journal":{"name":"Communications Biology","volume":"7 1","pages":"1467"},"PeriodicalIF":5.2,"publicationDate":"2024-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11549439/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142616320","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

scGraphformer: unveiling cellular heterogeneity and interactions in scRNA-seq data using a scalable graph transformer network. scGraphformer：利用可扩展的图转换器网络揭示 scRNA-seq 数据中的细胞异质性和相互作用。

IF 8.3 1区生物学

Communications Biology Pub Date : 2024-11-08 DOI: 10.1038/s42003-024-07154-w

Xingyu Fan, Jiacheng Liu, Yaodong Yang, Chunbin Gu, Yuqiang Han, Bian Wu, Yirong Jiang, Guangyong Chen, Pheng-Ann Heng

{"title":"scGraphformer: unveiling cellular heterogeneity and interactions in scRNA-seq data using a scalable graph transformer network.","authors":"Xingyu Fan, Jiacheng Liu, Yaodong Yang, Chunbin Gu, Yuqiang Han, Bian Wu, Yirong Jiang, Guangyong Chen, Pheng-Ann Heng","doi":"10.1038/s42003-024-07154-w","DOIUrl":"10.1038/s42003-024-07154-w","url":null,"abstract":"The precise classification of cell types from single-cell RNA sequencing (scRNA-seq) data is pivotal for dissecting cellular heterogeneity in biological research. Traditional graph neural network (GNN) models are constrained by reliance on predefined graphs, limiting the exploration of complex cell-to-cell relationships. We introduce scGraphformer, a transformer-based GNN that transcends these limitations by learning an all-encompassing cell-cell relational network directly from scRNA-seq data. Through an iterative refinement process, scGraphformer constructs a dense graph structure that captures the full spectrum of cellular interactions. This comprehensive approach enables the identification of subtle and previously obscured cellular patterns and relationships. Evaluated on multiple datasets, scGraphformer demonstrates superior performance in cell type identification compared to existing methods and showcases its scalability with large-scale datasets. Our method not only provides enhanced cell type classification ability but also reveals the underlying cell interactions, offering deeper insights into functional cellular relationships. The scGraphformer thus holds the potential to significantly advance the field of single-cell analysis and contribute to a more nuanced understanding of cellular behavior.","PeriodicalId":10552,"journal":{"name":"Communications Biology","volume":"7 1","pages":"1463"},"PeriodicalIF":8.3,"publicationDate":"2024-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11543810/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142603194","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 'photosynthetic C₁ pathway' links carbon assimilation and growth in California poplar. 光合作用 C1 途径 "将加州杨的碳同化和生长联系在一起。

IF 5.2 1区生物学

Communications Biology Pub Date : 2024-11-08 DOI: 10.1038/s42003-024-07142-0

Kolby J Jardine, Luiza Gallo, Melissa Roth, Shivani Upadhyaya, Trent Northen, Suzanne Kosina, Guillaume Tcherkez, Aymerick Eudes, Tomas Domigues, Markus Greule, Suman Som, Frank Keppler

{"title":"The 'photosynthetic C1 pathway' links carbon assimilation and growth in California poplar.","authors":"Kolby J Jardine, Luiza Gallo, Melissa Roth, Shivani Upadhyaya, Trent Northen, Suzanne Kosina, Guillaume Tcherkez, Aymerick Eudes, Tomas Domigues, Markus Greule, Suman Som, Frank Keppler","doi":"10.1038/s42003-024-07142-0","DOIUrl":"10.1038/s42003-024-07142-0","url":null,"abstract":"Although primarily studied in relation to photorespiration, serine metabolism in chloroplasts may play a key role in plant CO2 fertilization responses by linking CO2 assimilation with growth. Here, we show that the phosphorylated serine pathway is part of a 'photosynthetic C1 pathway' and demonstrate its high activity in foliage of a C3 tree where it rapidly integrates photosynthesis and C1 metabolism contributing to new biomass via methyl transfer reactions, imparting a large natural 13C-depleted signature. Using 13CO2-labelling, we show that leaf serine, the S-methyl group of leaf methionine, pectin methyl esters, and the associated methanol released during cell wall expansion during growth, are directly produced from photosynthetically-linked C1 metabolism, within minutes of light exposure. We speculate that the photosynthetic C1 pathway is highly conserved across the photosynthetic tree of life, is responsible for synthesis of the greenhouse gas methane, and may have evolved with oxygenic photosynthesis by providing a mechanism of directly linking carbon and ammonia assimilation with growth. Although the rise in atmospheric CO2 inhibits major metabolic pathways like photorespiration, our results suggest that the photosynthetic C1 pathway may accelerate and represents a missing link between enhanced photosynthesis and plant growth rates during CO2 fertilization under a changing climate.","PeriodicalId":10552,"journal":{"name":"Communications Biology","volume":"7 1","pages":"1469"},"PeriodicalIF":5.2,"publicationDate":"2024-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11549359/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142616314","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

ZBTB18 regulates cytokine expression and affects microglia/macrophage recruitment and commitment in glioblastoma. ZBTB18 可调节细胞因子的表达，并影响胶质母细胞瘤中小胶质细胞/巨噬细胞的招募和承诺。

IF 5.2 1区生物学

Communications Biology Pub Date : 2024-11-08 DOI: 10.1038/s42003-024-07144-y

Roberto Ferrarese, Kevin Joseph, Geoffroy Andrieux, Ira Verena Haase, Francesca Zanon, Eva Kling, Annalisa Izzo, Eyleen Corrales, Marius Schwabenland, Marco Prinz, Vidhya Madapusi Ravi, Melanie Boerries, Dieter Henrik Heiland, Maria Stella Carro

{"title":"ZBTB18 regulates cytokine expression and affects microglia/macrophage recruitment and commitment in glioblastoma.","authors":"Roberto Ferrarese, Kevin Joseph, Geoffroy Andrieux, Ira Verena Haase, Francesca Zanon, Eva Kling, Annalisa Izzo, Eyleen Corrales, Marius Schwabenland, Marco Prinz, Vidhya Madapusi Ravi, Melanie Boerries, Dieter Henrik Heiland, Maria Stella Carro","doi":"10.1038/s42003-024-07144-y","DOIUrl":"10.1038/s42003-024-07144-y","url":null,"abstract":"Glioma associated macrophages/microglia (GAMs) play an important role in glioblastoma (GBM) progression, due to their massive recruitment to the tumor site and polarization to a tumor promoting phenotype. GAMs secrete a variety of cytokines, which facilitate tumor cell growth and invasion, and prevent other immune cells from mounting an immune response against the tumor. Here, we demonstrate that zinc finger and BTB containing domain 18 (ZBTB18), a transcriptional repressor with tumor suppressive function in glioblastoma, impairs the production of key cytokines, which function as chemoattractant for GAMs. Consistently, we observe a reduced migration of GAMs when ZBTB18 is expressed by glioblastoma cells, both in cell culture and in vivo experiments. Moreover, RNA sequencing analysis shows that the presence of ZBTB18 in glioblastoma cells alters the commitment of conditioned microglia, suggesting the loss of the immune-suppressive phenotype and the acquisition of pro-inflammatory features. Thus, therapeutic approaches to increase ZBTB18 expression in GBM cells could represent an effective adjuvant to immune therapy in GBM.","PeriodicalId":10552,"journal":{"name":"Communications Biology","volume":"7 1","pages":"1472"},"PeriodicalIF":5.2,"publicationDate":"2024-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11549471/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142616364","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

Associative memory cells of encoding fear signals and anxiety are recruited by neuroligin-3-mediated synapse formation. 编码恐惧信号和焦虑的联想记忆细胞是通过神经胶质蛋白-3介导的突触形成招募的。

IF 8.3 1区生物学

Communications Biology Pub Date : 2024-11-08 DOI: 10.1038/s42003-024-07170-w

Bingchen Chen, Yun Zhang, Huajuan Xiao, Lei Wang, Jiayi Li, Yang Xu, Jin-Hui Wang

{"title":"Associative memory cells of encoding fear signals and anxiety are recruited by neuroligin-3-mediated synapse formation.","authors":"Bingchen Chen, Yun Zhang, Huajuan Xiao, Lei Wang, Jiayi Li, Yang Xu, Jin-Hui Wang","doi":"10.1038/s42003-024-07170-w","DOIUrl":"10.1038/s42003-024-07170-w","url":null,"abstract":"Acute severe stress may induce fear memory and anxiety. Their mechanisms are expectedly revealed to explore therapeutic strategies. We have investigated the recruitment of associative memory cells that encode stress signals to cause fear memory and anxiety by multidisciplinary approaches. In addition to fear memory and anxiety, the social stress by the resident/intruder paradigm leads to synapse interconnections between somatosensory S1-Tr and auditory cortical neurons in intruder mice. These S1-Tr cortical neurons become to receive convergent synapse innervations newly from the auditory cortex and innately from the thalamus as well as encode the stress signals including battle sound and somatic pain, i.e., associative memory neurons. Neuroligin-3 mRNA knockdown in the S1-Tr cortex precludes the recruitment of associative memory neurons and the onset of fear memory and anxiety. The stress-induced recruitment of associative memory cells in sensory cortices for stress-relevant fear memory and anxiety is based on neuroligin-3-mediated new synapse formation.","PeriodicalId":10552,"journal":{"name":"Communications Biology","volume":"7 1","pages":"1464"},"PeriodicalIF":8.3,"publicationDate":"2024-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11543854/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142603110","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

Sulfated galactofucan from Sargassum fusiforme protects against postmenopausal osteoporosis by regulating bone remodeling. 马尾藻中的硫酸化半乳聚糖通过调节骨重塑防止绝经后骨质疏松症。

IF 5.2 1区生物学

Communications Biology Pub Date : 2024-11-08 DOI: 10.1038/s42003-024-07097-2

Bao Yizhong, Fen Chen, Weihua Jin, Jihua Dai, Genxiang Mao, Boshan Song

{"title":"Sulfated galactofucan from Sargassum fusiforme protects against postmenopausal osteoporosis by regulating bone remodeling.","authors":"Bao Yizhong, Fen Chen, Weihua Jin, Jihua Dai, Genxiang Mao, Boshan Song","doi":"10.1038/s42003-024-07097-2","DOIUrl":"10.1038/s42003-024-07097-2","url":null,"abstract":"Osteoporosis is a degenerative bone disease highly prevalent in older women, causing high morbidity and mortality rates. Fourteen kinds of fucoidan were isolated from Sargassum fusiforme through acid (named as SFS), alkaline (SFJ) and water (SFW). SFW was passed through an anion exchange column to obtain SFW-0, SFW-0.5 and SFW-2. SFW-0.5 and SFW-2 were degraded to obtain different sulfate group contents SFW-x-M/S/O (x for 0.5 or 2). We further confirmed SFW-0.5-O was the most effective fraction of SFW. SFW-0.5-O may have alternating backbones of (Gal)n and (Fuc)n, and the main sulfation may be at C2/C3 of the Fuc/Gal residues. SFW-0.5-O inhibition of OC differentiation was associated with IRF-8 signaling; meanwhile, SFW-0.5-O promoted osteoblast differentiation and bone mineral nodule formation. SFW-0.5-O also effectively ameliorated osteoporosis symptom caused by estrogen deprivation in vivo. We uncovered that the fucoidan active fraction SFW-0.5-O demonstrated effective bone protection, may be exploited for osteoporosis therapy.","PeriodicalId":10552,"journal":{"name":"Communications Biology","volume":"7 1","pages":"1471"},"PeriodicalIF":5.2,"publicationDate":"2024-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11549216/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142616305","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

Endosome rupture enables enteroviruses from the family Picornaviridae to infect cells. 内质体破裂使皮卡病毒科的肠道病毒能够感染细胞。

IF 5.2 1区生物学

Communications Biology Pub Date : 2024-11-08 DOI: 10.1038/s42003-024-07147-9

Aygul Ishemgulova, Liya Mukhamedova, Zuzana Trebichalská, Veronika Rájecká, Pavel Payne, Lenka Šmerdová, Jana Moravcová, Dominik Hrebík, David Buchta, Karel Škubník, Tibor Füzik, Štěpánka Vaňáčová, Jiří Nováček, Pavel Plevka

{"title":"Endosome rupture enables enteroviruses from the family Picornaviridae to infect cells.","authors":"Aygul Ishemgulova, Liya Mukhamedova, Zuzana Trebichalská, Veronika Rájecká, Pavel Payne, Lenka Šmerdová, Jana Moravcová, Dominik Hrebík, David Buchta, Karel Škubník, Tibor Füzik, Štěpánka Vaňáčová, Jiří Nováček, Pavel Plevka","doi":"10.1038/s42003-024-07147-9","DOIUrl":"10.1038/s42003-024-07147-9","url":null,"abstract":"Membrane penetration by non-enveloped viruses is diverse and generally not well understood. Enteroviruses, one of the largest groups of non-enveloped viruses, cause diseases ranging from the common cold to life-threatening encephalitis. Enteroviruses enter cells by receptor-mediated endocytosis. However, how enterovirus particles or RNA genomes cross the endosome membrane into the cytoplasm remains unknown. Here we used cryo-electron tomography of infected cells to show that endosomes containing enteroviruses deform, rupture, and release the virus particles into the cytoplasm. Blocking endosome acidification with bafilomycin A1 reduced the number of particles that released their genomes, but did not prevent them from reaching the cytoplasm. Inhibiting post-endocytic membrane remodeling with wiskostatin promoted abortive enterovirus genome release in endosomes. The rupture of endosomes also occurs in control cells and after the endocytosis of very low-density lipoprotein. In summary, our results show that cellular membrane remodeling disrupts enterovirus-containing endosomes and thus releases the virus particles into the cytoplasm to initiate infection. Since the studied enteroviruses employ different receptors for cell entry but are delivered into the cytoplasm by cell-mediated endosome disruption, it is likely that most if not all enteroviruses, and probably numerous other viruses from the family Picornaviridae, can utilize endosome rupture to infect cells.","PeriodicalId":10552,"journal":{"name":"Communications Biology","volume":"7 1","pages":"1465"},"PeriodicalIF":5.2,"publicationDate":"2024-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11543853/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142603173","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

3D keloid spheroid model: Development and application for personalized drug response prediction. 三维瘢痕疙瘩球体模型：个性化药物反应预测的开发与应用。

IF 5.2 1区生物学

Communications Biology Pub Date : 2024-11-08 DOI: 10.1038/s42003-024-07194-2

YoungHwan Choi, Hyung-Suk Jang, Joonho Shim, Eunhye Yeo, Min-Hee Kim, Hyungrye Noh, Sejin Oh, Ji-Hye Park, Dongyoun Lee, Jong Hee Lee

{"title":"3D keloid spheroid model: Development and application for personalized drug response prediction.","authors":"YoungHwan Choi, Hyung-Suk Jang, Joonho Shim, Eunhye Yeo, Min-Hee Kim, Hyungrye Noh, Sejin Oh, Ji-Hye Park, Dongyoun Lee, Jong Hee Lee","doi":"10.1038/s42003-024-07194-2","DOIUrl":"10.1038/s42003-024-07194-2","url":null,"abstract":"Research on keloid is limited by the lack of proper in vitro and animal model reflecting in vivo status. Based on heterogeneity of keloid and important role of endothelial cells in its pathogenesis, a novel 3D in vitro keloid spheroid prepared with keloid fibroblasts and endothelial cells was evaluated in this study. Commercial cell lines of keloid fibroblasts and endothelial cells were used at various cellular ratios to generate keloid spheroids to determine the optimal condition. Keloid spheroids from three keloid patients were also made and their usefulness as in vitro models, including their responses to drugs, were assessed. Spheroids with higher endothelial cell proportions exhibited increased viability and propagation ability. Patient-derived keloid spheroids showed heterogeneity which might reflect individual clinical conditions. The optimal ratio of fibroblasts to endothelial cells was determined to be 4:1 for keloid spheroids based on gene expression and viability analyses. Patient-derived keloid spheroid showed better keloidal changes in genetic expressions than 2D monolayer culture. Spheroids exhibited varied responses and resistance to each drug used for keloids, depending on the cell type used. 3D keloid spheroids might provide an effective in vitro model for investigating disease pathogenesis and appropriate treatment modalities for future precision medicine.","PeriodicalId":10552,"journal":{"name":"Communications Biology","volume":"7 1","pages":"1470"},"PeriodicalIF":5.2,"publicationDate":"2024-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11549223/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142616137","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

Spatial transcriptomics reveals strong association between SFRP4 and extracellular matrix remodeling in prostate cancer. 空间转录组学揭示了 SFRP4 与前列腺癌细胞外基质重塑之间的密切联系。

IF 8.3 1区生物学

Communications Biology Pub Date : 2024-11-08 DOI: 10.1038/s42003-024-07161-x

Maria K Andersen, Sebastian Krossa, Elise Midtbust, Christine A Pedersen, Maximilian Wess, Therese S Høiem, Trond Viset, Øystein Størkersen, Ingunn Nervik, Elise Sandsmark, Helena Bertilsson, Guro F Giskeødegård, Morten B Rye, May-Britt Tessem

{"title":"Spatial transcriptomics reveals strong association between SFRP4 and extracellular matrix remodeling in prostate cancer.","authors":"Maria K Andersen, Sebastian Krossa, Elise Midtbust, Christine A Pedersen, Maximilian Wess, Therese S Høiem, Trond Viset, Øystein Størkersen, Ingunn Nervik, Elise Sandsmark, Helena Bertilsson, Guro F Giskeødegård, Morten B Rye, May-Britt Tessem","doi":"10.1038/s42003-024-07161-x","DOIUrl":"10.1038/s42003-024-07161-x","url":null,"abstract":"Prostate tumor heterogeneity is a major obstacle when studying the biological mechanisms of molecular markers. Increased gene expression levels of secreted frizzled-related protein 4 (SFRP4) is a biomarker in aggressive prostate cancer. To understand how SFRP4 relates to prostate cancer we performed comprehensive spatial and multiomics analysis of the same prostate cancer tissue samples. The experimental workflow included spatial transcriptomics, bulk transcriptomics, proteomics, DNA methylomics and tissue staining. SFRP4 mRNA was predominantly located in cancer stroma, produced by fibroblasts and smooth muscle cells, and co-expressed with extracellular matrix components. We also confirmed that higher SFRP4 gene expression is associated with cancer aggressiveness. Gene expression of SFRP4 was affected by gene promotor methylation. Surprisingly, the high mRNA levels did not reflect SFRP4 protein levels, which was much lower. This study contributes previously unknown insights of SFRP4 mRNA in the prostate tumor environment that potentially can improve diagnosis and treatment.","PeriodicalId":10552,"journal":{"name":"Communications Biology","volume":"7 1","pages":"1462"},"PeriodicalIF":8.3,"publicationDate":"2024-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11543834/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142603271","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

Targeting protein homeostasis with small molecules as a strategy for the development of pan-coronavirus antiviral therapies. 将小分子靶向蛋白稳态作为开发泛冠状病毒抗病毒疗法的一种策略。

IF 8.3 1区生物学

Communications Biology Pub Date : 2024-11-07 DOI: 10.1038/s42003-024-07143-z

Yu-Qian Mao, Shahrzad Jahanshahi, Ramy Malty, David A J Van Ommen, Yimei Wan, Trevor M Morey, Stephanie H W Chuang, Veronika Pavlova, Choudhary Ahmed, Subha Dahal, Funing Lin, Maria Mangos, Jocelyn Nurtanto, Yuetong Song, Terek Been, Natasha Christie-Holmes, Scott D Gray-Owen, Mohan Babu, Amy P Wong, Robert A Batey, Liliana Attisano, Alan Cochrane, Walid A Houry

{"title":"Targeting protein homeostasis with small molecules as a strategy for the development of pan-coronavirus antiviral therapies.","authors":"Yu-Qian Mao, Shahrzad Jahanshahi, Ramy Malty, David A J Van Ommen, Yimei Wan, Trevor M Morey, Stephanie H W Chuang, Veronika Pavlova, Choudhary Ahmed, Subha Dahal, Funing Lin, Maria Mangos, Jocelyn Nurtanto, Yuetong Song, Terek Been, Natasha Christie-Holmes, Scott D Gray-Owen, Mohan Babu, Amy P Wong, Robert A Batey, Liliana Attisano, Alan Cochrane, Walid A Houry","doi":"10.1038/s42003-024-07143-z","DOIUrl":"10.1038/s42003-024-07143-z","url":null,"abstract":"The COVID-19 pandemic has created a global health crisis, with challenges arising from the ongoing evolution of the SARS-CoV-2 virus, the emergence of new strains, and the long-term effects of COVID-19. Aiming to overcome the development of viral resistance, our study here focused on developing broad-spectrum pan-coronavirus antiviral therapies by targeting host protein quality control mechanisms essential for viral replication. Screening an in-house compound library led to the discovery of three candidate compounds targeting cellular proteostasis. The three compounds are (1) the nucleotide analog cordycepin, (2) a benzothiozole analog, and (3) an acyldepsipeptide analog initially developed as part of a campaign to target the mitochondrial ClpP protease. These compounds demonstrated dose-dependent efficacy against multiple coronaviruses, including SARS-CoV-2, effectively inhibiting viral replication in vitro as well as in lung organoids. Notably, the compounds also showed efficacy against SARS-CoV-2 delta and omicron strains. As part of this work, we developed a BSL2-level cell-integrated SARS-CoV-2 replicon, which could serve as a valuable tool for high-throughput screening and studying intracellular viral replication. Our study should aid in the advancement of antiviral drug development efforts.","PeriodicalId":10552,"journal":{"name":"Communications Biology","volume":"7 1","pages":"1460"},"PeriodicalIF":8.3,"publicationDate":"2024-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11543989/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142603290","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