Lea Melzener, Lieke Schaeken, Marion Fros, Tobias Messmer, Dhruv Raina, Annemarie Kiessling, Tessa van Haaften, Sergio Spaans, Arin Doǧan, Mark J. Post, Joshua E. Flack
{"title":"Optimisation of cell fate determination for cultivated muscle differentiation","authors":"Lea Melzener, Lieke Schaeken, Marion Fros, Tobias Messmer, Dhruv Raina, Annemarie Kiessling, Tessa van Haaften, Sergio Spaans, Arin Doǧan, Mark J. Post, Joshua E. Flack","doi":"10.1038/s42003-024-07201-6","DOIUrl":"10.1038/s42003-024-07201-6","url":null,"abstract":"Production of cultivated meat requires defined medium formulations for the robust differentiation of myogenic cells into mature skeletal muscle fibres in vitro. Although these formulations can drive myogenic differentiation levels comparable to serum-starvation-based protocols, the resulting cultures are often heterogeneous, with a significant proportion of cells not participating in myofusion, limiting maturation of the muscle. To address this problem, we employed RNA sequencing to analyse heterogeneity in differentiating bovine satellite cells at single-nucleus resolution, identifying distinct cellular subpopulations including proliferative cells that fail to exit the cell cycle and quiescent ‘reserve cells’ that do not commit to myogenic differentiation. Our findings indicate that the MEK/ERK, NOTCH, and RXR pathways are active during the initial stages of myogenic cell fate determination, and by targeting these pathways, we can promote cell cycle exit while reducing reserve cell formation. This optimised medium formulation consistently yields fusion indices close to 100% in 2D culture. Furthermore, we demonstrate that these conditions enhance myotube formation and actomyosin accumulation in 3D bovine skeletal muscle constructs, providing proof of principle for the generation of highly differentiated cultivated muscle with excellent mimicry to traditional muscle. Single-nucleus RNA sequencing gives insights into heterogeneity during bovine skeletal muscle differentiation, informing the design of improved medium formulations for cultivated meat production.","PeriodicalId":10552,"journal":{"name":"Communications Biology","volume":" ","pages":"1-12"},"PeriodicalIF":5.2,"publicationDate":"2024-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11557827/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142616275","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":"Distinct causes underlie double-peaked trilobite morphological disparity in cephalic shape.","authors":"Harriet B Drage, Stephen Pates","doi":"10.1038/s42003-024-07221-2","DOIUrl":"10.1038/s42003-024-07221-2","url":null,"abstract":"<p><p>Trilobite cephalic shape disparity varied through geological time and was integral to their ecological niche diversity, and so is widely used for taxonomic assignments. To fully appreciate trilobite cephalic evolution, we must understand how this disparity varies and the factors responsible. We explore trilobite cephalic disparity using a dataset of 983 cephalon outlines of c. 520 species, analysing the associations between cephalic morphometry and taxonomic assignment and geological Period. Elliptical Fourier transformation visualised as a Principal Components Analysis suggests significant differences in morphospace occupation and in disparity measures between the groups. Cephalic shape disparity peaks in the Ordovician and Devonian. The Cambrian-Ordovician expansion of morphospace occupation reflects radiations to new niches, with all trilobite orders established by the late Ordovician. In comparison, the Silurian-Devonian expansion seems solely a result of within-niche diversification. Linear Discriminant Analyses cross-validation, average cephalon shapes, and centroid distances demonstrate that, except for Harpida and the Cambrian and Ordovician Periods, order and geological Period cannot be robustly predicted for an unknown trilobite. Further, k-means clustering analyses suggest the total dataset naturally subdivides into only seven groups that do not correspond with taxonomy, though k-means clusters do decrease in number through the Palaeozoic, aligning with findings of decreasing disparity.</p>","PeriodicalId":10552,"journal":{"name":"Communications Biology","volume":"7 1","pages":"1490"},"PeriodicalIF":5.2,"publicationDate":"2024-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11557869/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142616190","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":"Synthetic indole derivatives as an antibacterial agent inhibiting respiratory metabolism of multidrug-resistant gram-positive bacteria.","authors":"Nishtha Chandal, Ritu Kalia, Akash Dey, Rushikesh Tambat, Nisha Mahey, Sanjay Jachak, Hemraj Nandanwar","doi":"10.1038/s42003-024-06996-8","DOIUrl":"10.1038/s42003-024-06996-8","url":null,"abstract":"<p><p>The survival of modern medicine depends heavily on the effective prevention and treatment of bacterial infections, are threatened by antibacterial resistance. The increasing use of antibiotics and lack of stewardship have led to an increase in antibiotic-resistant pathogens, so the growing issue of resistance can be resolved by emphasizing chemically synthesized antibiotics. This study discovered SMJ-2, a synthetic indole derivative, is effective against all multidrug-resistant gram-positive bacteria. SMJ-2 has multiple targets of action, but the primary mechanism inhibits respiratory metabolism and membrane potential disruption. SMJ-2 was discovered to interfere with the mevalonate pathway, ultimately preventing the synthesis of farnesyl diphosphate, a precursor to the antioxidant staphyloxanthin, eventually releasing reactive oxygen species, and leading phagocytic cells to destroy pathogens. Additionally, no discernible biochemical and histopathological alterations were found in the mouse acute toxicity model. This study emphasizes mechanistic insights into SMJ-2 as a potential antibacterial with an unusual method of action.</p>","PeriodicalId":10552,"journal":{"name":"Communications Biology","volume":"7 1","pages":"1489"},"PeriodicalIF":5.2,"publicationDate":"2024-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11557839/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142616307","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}
Laura Howard, Yuki Ishikawa, Tomohiko Katayama, Sung-Joon Park, Matthew J. Hill, Derek J. Blake, Kohji Nishida, Ryuhei Hayashi, Andrew J. Quantock
{"title":"Single-cell transcriptomics reveals the molecular basis of human iPS cell differentiation into ectodermal ocular lineages","authors":"Laura Howard, Yuki Ishikawa, Tomohiko Katayama, Sung-Joon Park, Matthew J. Hill, Derek J. Blake, Kohji Nishida, Ryuhei Hayashi, Andrew J. Quantock","doi":"10.1038/s42003-024-07130-4","DOIUrl":"10.1038/s42003-024-07130-4","url":null,"abstract":"The generation of a self-formed, ectodermal, autonomous multi-zone (SEAM) from human induced pluripotent stem cells (hiPSCs) offers a unique perspective to study the dynamics of ocular cell differentiation over time. Here, by utilising single-cell transcriptomics, we have (i) identified, (ii) molecularly characterised and (iii) ascertained the developmental trajectories of ectodermally-derived ocular cell populations which emerge within SEAMs as they form. Our analysis reveals interdependency between tissues of the early eye and delineates the sequential formation and maturation of distinct cell types over a 12-week period. We demonstrate a progression from pluripotency through to tissue specification and differentiation which encompasses both surface ectodermal and neuroectodermal ocular lineages and the generation of iPSC-derived components of the developing cornea, conjunctiva, lens, and retina. Our findings not only advance the understanding of ocular development in a stem cell-based system of human origin, but also establish a robust methodological paradigm for exploring cellular and molecular dynamics during SEAM formation at single-cell resolution and highlight the potential of hiPSC-derived systems as powerful platforms for modelling human eye development and disease. Single-cell transcriptomic analyses delineate the differentiation of human iPSCs into ectodermal ocular lineages, highlighting defined developmental trajectories and the sequential formation and maturation of distinct ocular cell types in vitro.","PeriodicalId":10552,"journal":{"name":"Communications Biology","volume":" ","pages":"1-15"},"PeriodicalIF":5.2,"publicationDate":"2024-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11557866/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142616304","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":"Molecular mechanisms of MAZ targeting up-regulation of NDUFS3 expression to promote malignant progression in melanoma.","authors":"Yu Feng, Qinxuan Ni, Na Wu, Taiyu Xie, Fang Yun, Xuedan Zhang, Lingnan Gao, Yanlong Gai, Enjiang Li, Xiaojia Yi, Junlin Xie, Qiao Zhang, Zhe Yang, Buqing Sai, Yingmin Kuang, Yuechun Zhu","doi":"10.1038/s42003-024-07209-y","DOIUrl":"10.1038/s42003-024-07209-y","url":null,"abstract":"<p><p>Myc-associated Zinc-finger Protein (MAZ) has been implicated in the malignant progression of various tumors. However, its expression and functional relationship of MAZ in melanoma have not been previously investigated. This study confirms elevated expression of MAZ in melanoma, correlating with poor patient prognosis. Furthermore, our findings demonstrate that MAZ enhances melanoma progression by promoting proliferation, migration and invasion. It is worth noting that we found that MAZ can target and regulate the transcription of NADH dehydrogenase [ubiquinone] iron-sulfur protein 3 (NDUFS3), a core subunit of mitochondrial complex I, to enhance mitochondrial metabolism and thus promote malignant progression of melanoma. Predictive modeling indicates that the co-expression of MAZ and NDUFS3 could serve as a potential prognostic marker for melanoma patients.</p>","PeriodicalId":10552,"journal":{"name":"Communications Biology","volume":"7 1","pages":"1491"},"PeriodicalIF":5.2,"publicationDate":"2024-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11557950/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142616255","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":"Neural reward system reflects individual value comparison strategy in cost-benefit decisions","authors":"Zarah Le Houcq Corbi, Alexander Soutschek","doi":"10.1038/s42003-024-07210-5","DOIUrl":"10.1038/s42003-024-07210-5","url":null,"abstract":"A core assumption in decision neuroscience is that individuals decide between options by comparing option-specific subjective reward values. Psychological accounts challenge this view and suggest that decisions are better explained by comparisons between choice attributes than by comparisons between option-specific values, casting doubts on the interpretation of activation in the neural reward system as subjective value signals. Here, we provide neuroimaging and pharmacological evidence that value-related neural activity follows the value comparison strategy employed by an individual on the psychological level. Neural model comparisons reveal that activation in the striatum, rather than generally reflecting attribute-wise or option-wise value comparisons, reflects the value comparison strategy that provides the best explanation for an individual’s choice behavior. Strikingly, manipulating activation in the dopaminergic reward system reveals that dopamine antagonism counteracts the engagement in an individual’s dominant value comparison strategy. Together, our findings provide evidence for the biological plausibility of psychological accounts of decision making and emphasize the importance of neural model comparisons to prevent misinterpretations of brain activation. Converging fMRI and pharmacological evidence suggests that the neural reward system encodes utility according to an agent’s preferred values comparison strategy.","PeriodicalId":10552,"journal":{"name":"Communications Biology","volume":" ","pages":"1-10"},"PeriodicalIF":5.2,"publicationDate":"2024-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11557971/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142616260","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}
Fei-Ju Li, Lora Starrs, Anukriti Mathur, Daniel Enosi Tuipulotu, Si Ming Man, Gaetan Burgio
{"title":"Interferon signalling and non-canonical inflammasome activation promote host protection against multidrug-resistant Acinetobacter baumannii.","authors":"Fei-Ju Li, Lora Starrs, Anukriti Mathur, Daniel Enosi Tuipulotu, Si Ming Man, Gaetan Burgio","doi":"10.1038/s42003-024-07204-3","DOIUrl":"10.1038/s42003-024-07204-3","url":null,"abstract":"<p><p>Multidrug-resistant (MDR) Acinetobacter baumannii are of major concern worldwide due to their resistance to last resort carbapenem and polymyxin antibiotics. To develop an effective treatment strategy, it is critical to better understand how an A. baumannii MDR bacterium interacts with its mammalian host. Pattern-recognition receptors sense microbes, and activate the inflammasome pathway, leading to pro-inflammatory cytokine production and programmed cell death. Here, we examined the effects of a systemic MDR A. baumannii infection and found that MDR A. baumannii activate the NLRP3 inflammasome complex predominantly via the non-canonical caspase-11-dependent pathway. We show that caspase-1 and caspase-11-deficient mice are protected from a virulent MDR A. baumannii strain by maintaining a balance between protective and deleterious inflammation. Caspase-11-deficient mice also compromise between effector cell recruitment, phagocytosis, and programmed cell death in the lung during infection. Importantly, we found that cytosolic immunity - mediated by guanylate-binding protein 1 (GBP1) and type I interferon signalling - orchestrates caspase-11-dependent inflammasome activation. Together, our results suggest that non-canonical inflammasome activation via the (Interferon) IFN pathway plays a critical role in the host response against MDR A. baumannii infection.</p>","PeriodicalId":10552,"journal":{"name":"Communications Biology","volume":"7 1","pages":"1494"},"PeriodicalIF":5.2,"publicationDate":"2024-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11557958/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142635918","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}
Raquel Peixoto, Christian R Voolstra, Lisa Y Stein, Philip Hugenholtz, Joana Falcao Salles, Shady A Amin, Max Häggblom, Ann Gregory, Thulani P Makhalanyane, Fengping Wang, Nadège Adoukè Agbodjato, Yinzhao Wang, Nianzhi Jiao, Jay T Lennon, Antonio Ventosa, Patrik M Bavoil, Virginia Miller, Jack A Gilbert
{"title":"Microbial solutions must be deployed against climate catastrophe.","authors":"Raquel Peixoto, Christian R Voolstra, Lisa Y Stein, Philip Hugenholtz, Joana Falcao Salles, Shady A Amin, Max Häggblom, Ann Gregory, Thulani P Makhalanyane, Fengping Wang, Nadège Adoukè Agbodjato, Yinzhao Wang, Nianzhi Jiao, Jay T Lennon, Antonio Ventosa, Patrik M Bavoil, Virginia Miller, Jack A Gilbert","doi":"10.1038/s42003-024-07108-2","DOIUrl":"10.1038/s42003-024-07108-2","url":null,"abstract":"","PeriodicalId":10552,"journal":{"name":"Communications Biology","volume":"7 1","pages":"1466"},"PeriodicalIF":5.2,"publicationDate":"2024-11-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11555260/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142616251","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}
Thayná M Avelino, Samarah V Harb, Douglas Adamoski, Larissa C M Oliveira, Cintia D S Horinouchi, Rafael J de Azevedo, Rafael A Azoubel, Vanessa K Thomaz, Fernanda A H Batista, Marcos Akira d'Ávila, Pedro L Granja, Ana Carolina M Figueira
{"title":"Unveiling the impact of hypodermis on gene expression for advancing bioprinted full-thickness 3D skin models.","authors":"Thayná M Avelino, Samarah V Harb, Douglas Adamoski, Larissa C M Oliveira, Cintia D S Horinouchi, Rafael J de Azevedo, Rafael A Azoubel, Vanessa K Thomaz, Fernanda A H Batista, Marcos Akira d'Ávila, Pedro L Granja, Ana Carolina M Figueira","doi":"10.1038/s42003-024-07106-4","DOIUrl":"10.1038/s42003-024-07106-4","url":null,"abstract":"<p><p>3D skin models have been explored as an alternative method to the use of animals in research and development. Usually, human skin equivalents comprise only epidermis or epidermis/dermis layers. Herein, we leverage 3D bioprinting technology to fabricate a full-thickness human skin equivalent with hypodermis (HSEH). The collagen hydrogel-based structure provides a mimetic environment for skin cells to adhere, proliferate and differentiate. The effective incorporation of the hypodermis layer is evidenced by scanning electron microscopy, immunofluorescence, and hematoxylin and eosin staining. The transcriptome results underscore the pivotal role of the hypodermis in orchestrating the genetic expression of a multitude of genes vital for skin functionality, including hydration, development and differentiation. Accordingly, we evidence the paramount significance of full-thickness human skin equivalents with hypodermis layer to provide an accurate in vitro platform for disease modeling and toxicology studies.</p>","PeriodicalId":10552,"journal":{"name":"Communications Biology","volume":"7 1","pages":"1437"},"PeriodicalIF":5.2,"publicationDate":"2024-11-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11555214/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142616318","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}
Gabriele Coluccino, Alessandro Negro, Antonio Filippi, Camilla Bean, Valentina Pia Muraca, Clarissa Gissi, Diana Canetti, Maria Chiara Mimmi, Elisa Zamprogno, Francesco Ciscato, Laura Acquasaliente, Vincenzo De Filippis, Marina Comelli, Michela Carraro, Andrea Rasola, Christoph Gerle, Paolo Bernardi, Alessandra Corazza, Giovanna Lippe
{"title":"N-terminal cleavage of cyclophilin D boosts its ability to bind F-ATP synthase.","authors":"Gabriele Coluccino, Alessandro Negro, Antonio Filippi, Camilla Bean, Valentina Pia Muraca, Clarissa Gissi, Diana Canetti, Maria Chiara Mimmi, Elisa Zamprogno, Francesco Ciscato, Laura Acquasaliente, Vincenzo De Filippis, Marina Comelli, Michela Carraro, Andrea Rasola, Christoph Gerle, Paolo Bernardi, Alessandra Corazza, Giovanna Lippe","doi":"10.1038/s42003-024-07172-8","DOIUrl":"10.1038/s42003-024-07172-8","url":null,"abstract":"<p><p>Cyclophilin (CyP) D is a regulator of the mitochondrial F-ATP synthase. Here we report the discovery of a form of CyPD lacking the first 10 (mouse) or 13 (human) N-terminal residues (ΔN-CyPD), a protein region with species-specific features. NMR studies on recombinant human full-length CyPD (FL-CyPD) and ΔN-CyPD form revealed that the N-terminus is highly flexible, in contrast with the rigid globular part. We have studied the interactions of FL and ΔN-CyPD with F-ATP synthase at the OSCP subunit, a site where CyPD binding inhibits catalysis and favors the transition of the enzyme complex to the permeability transition pore. At variance from FL-CyPD, ΔN-CyPD binds OSCP in saline media, indicating that the N-terminus substantially decreases the binding affinity for OSCP. We also provide evidence that calpain 1 is responsible for generation of ΔN-CyPD in cells. Altogether, our work suggests the existence of a novel mechanism of modulation of CyPD through cleavage of its N-terminus that may have significant pathophysiological implications.</p>","PeriodicalId":10552,"journal":{"name":"Communications Biology","volume":"7 1","pages":"1486"},"PeriodicalIF":5.2,"publicationDate":"2024-11-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11555324/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142616274","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}