{"title":"Derivation of human post-mitotic cardiomyocytes from tetraploid iPSCs.","authors":"Ittetsu Nakajima, Mitsuyoshi Shimane, Grace Holmstrom, Yuichiro Miyaoka","doi":"10.1038/s42003-026-10763-2","DOIUrl":"https://doi.org/10.1038/s42003-026-10763-2","url":null,"abstract":"<p><p>Human induced pluripotent stem cell (iPSC)-derived cardiomyocytes (iPS-CMs) have great potential in regenerative medicine. However, iPS-CMs are immature and resemble fetal cardiomyocytes, restricting their application. Fetal cardiomyocytes in the human heart are diploid and proliferating, but gradually lose their proliferative potential during maturation. Most human cardiomyocytes eventually become tetraploid, but iPS-CMs cannot replicate this tetraploidization and remain immature with the current differentiation techniques. To overcome this problem, we fused diploid iPSCs to establish tetraploid iPSCs and differentiated them into cardiomyocytes (4N-iPS-CMs) to replicate the tetraploidy. As we expected, we found that 4N-iPS-CMs had more similar gene expression profiles, improved mitochondrial functions, contractile impedance, and resistance to a potassium blocker in post-mitotic cardiomyocytes than conventional iPS-CMs. In addition, we successfully generated 4N-iPS-CMs from two individuals to mix two different genetic backgrounds. Thus, we demonstrated a unique strategy for generating human post-mitotic cardiomyocyte-like cells by generating tetraploid iPSCs.</p>","PeriodicalId":10552,"journal":{"name":"Communications Biology","volume":"9 1","pages":""},"PeriodicalIF":5.8,"publicationDate":"2026-08-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13483045/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148789160","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}
Edwin M van Oosten, Wietske Kieboom, Anita D M Hoogendoorn, Stijn L Berendsen, Julia Haerkens, Marieke M E van der Maden, Eva Hruba, Devin Veerman, Anja Bufe, Seba Almedawar, Andries D van der Meer, Tomas Barta, Rob W J Collin, Alejandro Garanto
{"title":"Long-term daily light exposure boosts human retinal organoid differentiation.","authors":"Edwin M van Oosten, Wietske Kieboom, Anita D M Hoogendoorn, Stijn L Berendsen, Julia Haerkens, Marieke M E van der Maden, Eva Hruba, Devin Veerman, Anja Bufe, Seba Almedawar, Andries D van der Meer, Tomas Barta, Rob W J Collin, Alejandro Garanto","doi":"10.1038/s42003-026-10216-w","DOIUrl":"10.1038/s42003-026-10216-w","url":null,"abstract":"<p><p>Induced pluripotent stem cell-derived retinal organoids (ROs) have become promising personalized models to study inherited retinal diseases (IRDs) and develop new therapies. Although ROs mimic key retinal features and show some light responsiveness, their differentiation and maturation remain limited and lengthy. We hypothesize that standard dark culture conditions limit the expression of genes and proteins related to retinal function, delaying differentiation, and hindering disease modeling. Here, we investigate whether daily light exposure promotes photoreceptor maturation by exposing ROs to six hours of daily light starting from day 70 in vitro. Light conditioning accelerates differentiation of late-born cell types, especially rod photoreceptors, without signs of increased stress or cell death. Our findings suggest that daily light exposure enhances RO differentiation, opening avenues to investigate molecular and cellular phenotypes in IRDs and accelerate therapy development in more relevant functional models.</p>","PeriodicalId":10552,"journal":{"name":"Communications Biology","volume":"9 1","pages":""},"PeriodicalIF":5.8,"publicationDate":"2026-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13470357/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148724055","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}
Paul Muhle, Jonas von Itter, Anne Jung, Bendix Labeit, Ivy Cheng, Inga Claus, Andreas Wollbrink, Joachim Gross, Rainer Dziewas, Sonja Suntrup-Krueger
{"title":"Frequency-specific cortical subnetworks support fast human swallowing.","authors":"Paul Muhle, Jonas von Itter, Anne Jung, Bendix Labeit, Ivy Cheng, Inga Claus, Andreas Wollbrink, Joachim Gross, Rainer Dziewas, Sonja Suntrup-Krueger","doi":"10.1038/s42003-026-10751-6","DOIUrl":"10.1038/s42003-026-10751-6","url":null,"abstract":"<p><p>Fast, highly constrained sensorimotor acts require rapid coordination of distributed cortical systems on subsecond timescales. Here, we used source-resolved magnetoencephalography to characterise time-locked cortical connectivity during voluntary swallowing in 74 healthy adults. Cluster-based network statistics revealed focal swallowing-related connectivity changes confined to anatomically selective subnetworks. Undirected phase-lagged connectivity identified theta- and low-gamma weighted phase lag index (wPLI) effects involving somatosensory, motor, supramarginal, and insular regions. Directed connectivity revealed sparse high-gamma phase slope index (PSI) subnetworks centred on the primary somatosensory cortex and anterior insula. Time-window analyses demonstrated temporally evolving low-gamma interactions between posterior parietal and insular regions, while laterality analyses showed rightward theta-band directed asymmetries during later swallowing phases. In contrast, global graph-theoretical metrics and node-level hub measures remained largely stable after correction for multiple comparisons. These findings indicate that voluntary swallowing is supported by focal, frequency-specific, and temporally structured cortical interactions rather than broad global network reconfiguration.</p>","PeriodicalId":10552,"journal":{"name":"Communications Biology","volume":"9 1","pages":""},"PeriodicalIF":5.8,"publicationDate":"2026-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13451196/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148688653","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}
Erik LeRoy, JangKeun Kim, Helena Ruland, Nathan Schanzer, Anurag Sakharkar, Lucinda Innes, Zachary Feinstein, Daniel Zuniga Gamboa, Robert Chen, Mohith Reddy Arikatla, Kubra Can Kurt, Brian E Crucian, Michael A Schmidt, Christopher E Mason
{"title":"Long-term major histocompatibility complex class I suppression in astronauts and clinical implications.","authors":"Erik LeRoy, JangKeun Kim, Helena Ruland, Nathan Schanzer, Anurag Sakharkar, Lucinda Innes, Zachary Feinstein, Daniel Zuniga Gamboa, Robert Chen, Mohith Reddy Arikatla, Kubra Can Kurt, Brian E Crucian, Michael A Schmidt, Christopher E Mason","doi":"10.1038/s42003-026-10550-z","DOIUrl":"10.1038/s42003-026-10550-z","url":null,"abstract":"<p><p>Spaceflight can disrupt astronaut immunity, including sustained downregulation of Major Histocompatibility Complex (MHC) class I genes across missions ranging from the three-day Inspiration4 flight to long-duration International Space Station stays. MHC class I downregulation is a known mechanism of immune evasion in cancer and viral infection, potentially increasing health risks during and after spaceflight. The underlying mechanisms, clinical implications and therapeutic options remain underexplored. This Perspective discusses long-term risks associated with astronaut MHC class I suppression, proposes future research directions and outlines therapeutic approaches with broader relevance to related health challenges on Earth.</p>","PeriodicalId":10552,"journal":{"name":"Communications Biology","volume":"9 1","pages":""},"PeriodicalIF":5.8,"publicationDate":"2026-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13448508/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148683748","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}
Shuai Zhao, Siena Bush, Ivan O Rosas, Svetlana Reilly, Xander H T Wehrens
{"title":"Molecular mechanisms, therapeutic strategies, and inter-organ fibrosis crosstalk of Gla proteins in cardiovascular disease.","authors":"Shuai Zhao, Siena Bush, Ivan O Rosas, Svetlana Reilly, Xander H T Wehrens","doi":"10.1038/s42003-026-10740-9","DOIUrl":"10.1038/s42003-026-10740-9","url":null,"abstract":"<p><p>Gla proteins are a vitamin K-dependent family long studied for their roles in blood clotting and vascular calcification. This review examines their broader involvement in cardiovascular disease, particularly cardiac fibrosis. We highlight that their functions are context-dependent, varying with disease stage and cellular environment, and that several occur independently of γ-carboxylation, challenging the view that this modification is universally required for their function. By comparing fibrosis across the heart, lung, liver, and kidney, we distinguish shared from organ-specific mechanisms. Finally, we discuss prospective therapies, from vitamin K supplementation to receptor-targeted approaches, and the questions that remain before clinical translation.</p>","PeriodicalId":10552,"journal":{"name":"Communications Biology","volume":"9 1","pages":""},"PeriodicalIF":5.8,"publicationDate":"2026-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13462327/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148711754","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}
Susana Paredes-Zúñiga, Rebecca Veit, Kristine Østevold, Gerard Arrey, Johanna Wehrle, Dennis Frank, Johannes Oswald, Florian Veit, Theresa Schredelseker, Sandra Glauben, Jochen Holzschuh, Wolfgang Driever
{"title":"A genetic model for development, physiology and behavior of catecholamine-deficient zebrafish larvae.","authors":"Susana Paredes-Zúñiga, Rebecca Veit, Kristine Østevold, Gerard Arrey, Johanna Wehrle, Dennis Frank, Johannes Oswald, Florian Veit, Theresa Schredelseker, Sandra Glauben, Jochen Holzschuh, Wolfgang Driever","doi":"10.1038/s42003-026-10732-9","DOIUrl":"10.1038/s42003-026-10732-9","url":null,"abstract":"<p><p>Dopamine and noradrenaline have conserved roles in control of physiology and behaviors of vertebrates. However, vertebrate genetic models completely devoid of catecholamines are not available. We generated genetically catecholamine-free zebrafish larvae by combining mutations in all three genes involved in L-DOPA biosynthesis: the tyrosine hydroxylase genes th and th2, and tyrosinase tyr. Here we show that catecholamine-deficient 5 day-old zebrafish larvae are viable and develop an anatomically normal nervous system, including the full complement of catecholaminergic neuron somata and projections. In contrast, selected physiological functions that depend on catecholamines are impaired, including hatching and heart rate regulation upon temperature challenges. Spontaneous locomotion and optomotor behaviors are also impaired. Despite the changes observed, it is surprising that larvae develop a largely normal behavioral repertoire. Our model will be useful to investigate the activities of additional neurotransmitters expressed in catecholaminergic neurons, and how physiology and neural circuit function are regulated in the absence of catecholamines.</p>","PeriodicalId":10552,"journal":{"name":"Communications Biology","volume":"9 1","pages":""},"PeriodicalIF":5.8,"publicationDate":"2026-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13444079/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148677409","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}
Zigmunds Orlovskis, Ilva Nakurte, Ēriks Voroņins, Annija Kotova, Shah Dawood, Daniels Pugačevskis, Annija Andersone, Kārlis Trevors Blūms, Ivars Silamiķelis, Soon-Jae Lee
{"title":"Rhizophagus irregularis modulates neighbour-primed defences in Medicago truncatula against foliar pathogens via common mycelial network-mediated inter-plant signals.","authors":"Zigmunds Orlovskis, Ilva Nakurte, Ēriks Voroņins, Annija Kotova, Shah Dawood, Daniels Pugačevskis, Annija Andersone, Kārlis Trevors Blūms, Ivars Silamiķelis, Soon-Jae Lee","doi":"10.1038/s42003-026-10727-6","DOIUrl":"10.1038/s42003-026-10727-6","url":null,"abstract":"<p><p>Arbuscular mycorrhizal fungi (AMF) are ubiquitous root symbionts that form common mycelial networks (CMN), linking multiple plants underground. CMN are thought to contribute to information exchange between plants and to neighbour-primed defences, but the transcriptomic and metabolomic responses of receiver plants connected through CMN remain poorly understood. In addition, the confounding effects of hyphal damage caused by CMN disconnection have not been clearly resolved. To assess the contribution of CMN integrity to neighbour-primed plant defences, we used the model AMF Rhizophagus irregularis to connect two Medicago truncatula plants and examined the effects of sender wounding and flg22 elicitation on receiver leaf responses and pathogen tolerance. We found that changes in receiver biotic stress and defence signalling pathways depend on CMN-mediated inter-plant signals rather than on damage to the mycelial network. These responses were associated with distinct changes in leaf isoprenoid production, including volatile monoterpene and triterpene compounds. CMN-mediated signals from stressed senders enhanced receiver resistance to Fusarium sporotrichoides while increasing susceptibility to Botrytis cinerea. These findings highlight the role of CMN in inter-plant signalling and pathogen-specific resistance and susceptibility, with implications for understanding plant community defence in natural and agricultural systems.</p>","PeriodicalId":10552,"journal":{"name":"Communications Biology","volume":"9 1","pages":""},"PeriodicalIF":5.8,"publicationDate":"2026-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13661613/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149179773","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":"Medial premotor cortex as a potential reservoir of reward expectancy signals influencing the primate frontoparietal network.","authors":"Keisuke Sehara, Masashi Kondo, Yuka Hirayama, Teppei Ebina, Masafumi Takaji, Akiya Watakabe, Ken-Ichi Inoue, Masahiko Takada, Tetsuo Yamamori, Masanori Matsuzaki","doi":"10.1038/s42003-026-10672-4","DOIUrl":"10.1038/s42003-026-10672-4","url":null,"abstract":"<p><p>Reward expectancy plays an important role in modulating cortical activity associated with motivation, selection, and preparation of subsequent goal-directed movements. However, it is unclear how it is represented in the primate frontoparietal cortex in a form that is separable from activity for motor execution. Here, using common marmosets performing a classical conditioning task with auditory cues, we conducted wide-field one-photon calcium imaging of frontoparietal and auditory cortices while recording orofacial and body movements. Reward expectancy that was separable from licking, eye movement, and hand movement was represented in the medial part of the dorsorostral premotor cortex (mPMdr), but not the central part. Granger causality analysis revealed information flows from mPMdr to widespread frontoparietal areas beyond its functional subnetwork, specifically during the delay period before reward delivery. Our results suggest that in non-human primates, mPMdr serves to retain reward expectancy to modulate the frontoparietal network for subsequent movements.</p>","PeriodicalId":10552,"journal":{"name":"Communications Biology","volume":"9 1","pages":""},"PeriodicalIF":5.8,"publicationDate":"2026-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13424355/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148629717","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":"Multivalent ion binding site identification with structure-based deep learning.","authors":"Igor Kozlovskii, Petr Popov","doi":"10.1038/s42003-026-10659-1","DOIUrl":"10.1038/s42003-026-10659-1","url":null,"abstract":"<p><p>Protein-ion interactions are essential for many cellular processes, including enzymatic catalysis, signaling, and allosteric regulation. However, mapping ion-binding sites experimentally remains labor-intensive and expensive. Here, we present BiteNet<sub>I</sub>, a structure-based deep learning model that uses 3D convolutional neural networks to simultaneously localize ion-binding centers and predict binding residues for 14 biologically relevant ions. Trained on a carefully curated dataset of over 10,000 high-resolution protein-ion complexes, in which near-identical binding sites are consistently annotated by transferring ions between homologous structures, BiteNet<sub>I</sub> shows strong generalization ability across diverse ions within a unified multitask architecture. On two different test benchmarks, BiteNet<sub>I</sub> achieves state-of-the-art performance compared to existing ion-binding predictors as well as to a more general method, AlphaFold3, when used to predict the entire structure of protein bound to ions. Finally, for physiologically relevant ions such as Ca<sup>2+</sup>, Na<sup>+</sup> and K<sup>+</sup>, BiteNet<sub>I</sub> achieves two- to three-fold improvement in accuracy.</p>","PeriodicalId":10552,"journal":{"name":"Communications Biology","volume":"9 1","pages":""},"PeriodicalIF":5.8,"publicationDate":"2026-07-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13434133/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148668695","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}