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A 3D printing UV-curing resin that enables continuous color change of elastomers 一种3D打印uv固化树脂,可使弹性体连续变色
IF 4.6 2区 综合性期刊
iScience Pub Date : 2025-06-09 DOI: 10.1016/j.isci.2025.112867
Yiyang Gao , Qihao Jiang , Yanming Liu
{"title":"A 3D printing UV-curing resin that enables continuous color change of elastomers","authors":"Yiyang Gao ,&nbsp;Qihao Jiang ,&nbsp;Yanming Liu","doi":"10.1016/j.isci.2025.112867","DOIUrl":"10.1016/j.isci.2025.112867","url":null,"abstract":"<div><div>This study introduces a UV-curing resin leveraging the Christiansen effect to achieve dynamic color modulation in phase-separated elastomers (PSE) through solvent composition and temperature control. By matching refractive indices between solvent (dimethyl phthalate/tributyl citrate) and polymer phases, PSE selectively transmits-specific wavelengths, enabling continuous color shifts from red to purple. The elastomers exhibit robust mechanical properties (&gt;600% elongation, &gt;300 kPa modulus) and function across a broad temperature range (−25°C–130°C). Compatible with 3D printing, the resin enables real-time solvent adjustments during fabrication, supporting spatially continuous color transitions without parameter modifications. This approach advances applications in adaptive optical devices, temperature-responsive displays, and multi-material 3D printing, offering a dye-free strategy for structural coloration in smart materials.</div></div>","PeriodicalId":342,"journal":{"name":"iScience","volume":"28 7","pages":"Article 112867"},"PeriodicalIF":4.6,"publicationDate":"2025-06-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144314416","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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
Diet and environment drive the convergence of gut microbiome in wild-released giant pandas and forest musk deer 野生大熊猫和森林麝的饮食和环境驱动肠道微生物群的趋同
IF 4.6 2区 综合性期刊
iScience Pub Date : 2025-06-07 DOI: 10.1016/j.isci.2025.112837
Chenyi Gao , Qiuyu Huang , Xinru Yang , Xinyuan Cui , Kaizhi Wen , Yue Liu , Chenyan Wang , Qinlong Dai , Jiadong Xie , Lifeng Zhu
{"title":"Diet and environment drive the convergence of gut microbiome in wild-released giant pandas and forest musk deer","authors":"Chenyi Gao ,&nbsp;Qiuyu Huang ,&nbsp;Xinru Yang ,&nbsp;Xinyuan Cui ,&nbsp;Kaizhi Wen ,&nbsp;Yue Liu ,&nbsp;Chenyan Wang ,&nbsp;Qinlong Dai ,&nbsp;Jiadong Xie ,&nbsp;Lifeng Zhu","doi":"10.1016/j.isci.2025.112837","DOIUrl":"10.1016/j.isci.2025.112837","url":null,"abstract":"<div><div>Reintroduction is important for recovering endangered species, and gut microbiome is crucial for successful wildlife reintroduction. This study utilized 16S rRNA high-throughput sequencing of 791 fecal samples to examine the gut microbial changes in giant pandas (<em>Ailuropoda melanoleuca</em>) and forest musk deer (<em>Moschus berezovskii</em>) across captivity, semi-release, and release stages. Our results revealed a similar transitional pattern in the gut microbiome of both species, with semi-release stage displaying an intermediate state between captive and wild microbiome. We also observed that both species are enriched in <em>Pseudomonas</em> and functional pathways related to amino acid metabolism, ATP-binding cassette transporters, and acetyl-CoA/propionyl-CoA carboxylase. Furthermore, the SourceTracker analysis indicated putative contributions of plant and soil microbiome to the gut microbiome of forest musk deer. These findings suggest that similar herbivorous diets and same environment may contribute to the convergence of gut microbiome. In conclusion, our study provides valuable insights for reintroducing endangered wildlife.</div></div>","PeriodicalId":342,"journal":{"name":"iScience","volume":"28 7","pages":"Article 112837"},"PeriodicalIF":4.6,"publicationDate":"2025-06-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144366120","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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
Cellular heterogeneity and patterning strategies as revealed by upper respiratory epithelium single cell atlas 上呼吸道上皮单细胞图谱揭示的细胞异质性和模式策略
IF 4.6 2区 综合性期刊
iScience Pub Date : 2025-06-07 DOI: 10.1016/j.isci.2025.112845
Alexander G. Foote , Xin Sun
{"title":"Cellular heterogeneity and patterning strategies as revealed by upper respiratory epithelium single cell atlas","authors":"Alexander G. Foote ,&nbsp;Xin Sun","doi":"10.1016/j.isci.2025.112845","DOIUrl":"10.1016/j.isci.2025.112845","url":null,"abstract":"<div><div>The upper respiratory tract, spanning the pharyngolaryngeal to tracheobronchial regions, enables breathing, vocalization, and frontline defense against airborne insults. We generated a cellular and molecular atlas of the mouse upper respiratory epithelium from pharynx/larynx to tracheobronchial carina by combining single-cell RNA sequencing with spatial validation. Our analysis revealed 18 epithelial cell types, organized into three spatially distinct compartments: <em>Tmprss11a</em>+ pharyngolaryngeal, <em>Nkx2-1</em>+ tracheobronchial, and <em>Dmbt1</em>+ submucosal glands. Stratified squamous pharyngolaryngeal zones displayed extensive and region-specific Keratin codes. Within the pseudostratified tracheobronchial epithelium, diverse luminal cells, including multiple varieties of club cells, exhibit marker-expression gradients along the proximal–distal axes. Lastly, analysis of the submucosal gland epithelium —which contains various cell types, including distinctive myoepithelial cells— revealed extensive diversity both among and within its cellular populations. This spatially resolved transcriptomic atlas elucidates how epithelial identity varies along the upper respiratory axes and will guide investigations into cellular dynamics in health and disease.</div></div>","PeriodicalId":342,"journal":{"name":"iScience","volume":"28 7","pages":"Article 112845"},"PeriodicalIF":4.6,"publicationDate":"2025-06-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144329824","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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
Belief updating in decision-variable space: More fine-grained choices attract future ones more strongly 决策变量空间中的信念更新:更细粒度的选择更能吸引未来的选择
IF 4.6 2区 综合性期刊
iScience Pub Date : 2025-06-07 DOI: 10.1016/j.isci.2025.112844
Heeseung Lee , Jaeseob Lim , Sang-Hun Lee
{"title":"Belief updating in decision-variable space: More fine-grained choices attract future ones more strongly","authors":"Heeseung Lee ,&nbsp;Jaeseob Lim ,&nbsp;Sang-Hun Lee","doi":"10.1016/j.isci.2025.112844","DOIUrl":"10.1016/j.isci.2025.112844","url":null,"abstract":"<div><div>When engaged in decision-making tasks, humans are known to create decision variables. Much effort has focused on the cognitive processes involved in forming decision variables. However, there is limited understanding of how decision variables, once formed, are utilized to adapt to the environment. We reason that decision-makers would benefit from updating their belief on decision variables. As one such belief updating, we hypothesize that commitment to a decision limits the range of possible beliefs about decision variables to align with the committed decision. This implies that past decisions not only attract future ones but also exert a greater pull when decisions are made with finer granularity—dubbed “granularity effect.” Here, we present the findings of seven psychophysical experiments that confirm these implications. Further, we offer a unified Bayesian account of the granularity effect, along with previously established decisional history effects, demonstrating how effectively humans leverage their probabilistic inference for adaptation.</div></div>","PeriodicalId":342,"journal":{"name":"iScience","volume":"28 7","pages":"Article 112844"},"PeriodicalIF":4.6,"publicationDate":"2025-06-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144329821","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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
Epigenetic regulation of intracellular branched-chain amino acid homeostasis maintains a normal lifespan 细胞内支链氨基酸稳态的表观遗传调控维持了正常的寿命
IF 4.6 2区 综合性期刊
iScience Pub Date : 2025-06-07 DOI: 10.1016/j.isci.2025.112846
Sejung Park , Yan Liu , Suji Lim , Hong-Yeoul Ryu , Seong Hoon Ahn
{"title":"Epigenetic regulation of intracellular branched-chain amino acid homeostasis maintains a normal lifespan","authors":"Sejung Park ,&nbsp;Yan Liu ,&nbsp;Suji Lim ,&nbsp;Hong-Yeoul Ryu ,&nbsp;Seong Hoon Ahn","doi":"10.1016/j.isci.2025.112846","DOIUrl":"10.1016/j.isci.2025.112846","url":null,"abstract":"<div><div>Cells experience a progressive decline in function and lifespan, accompanied by epigenetic changes. Here, we show that intracellular BCAA (icBCAA) homeostasis is regulated by histone H3K4 and H3K121 in budding yeast. Using a comprehensive H3/H4 mutant library, we identified residues essential for lifespan maintenance linked to BCAA metabolism. Among these, H3K4A/R and H3K121A mutations led to significant transcriptional changes in genes involved in BCAA biosynthesis and catabolism, accompanied by abnormally elevated icBCAA levels. Consistent with the upregulation of <em>BAT1</em>, <em>ILV6</em>, and <em>ADH1</em> genes in the H3K121A mutant, chromatin immunoprecipitation revealed increased H3K4me3 at their promoters. The genetic perturbation of <em>BAT1</em> and <em>BAT2</em> restored icBCAA balance and partially rescued lifespan defects in H3K4 or H3K121 mutants. Additionally, H3K4 and H3K121 mutations affected lifespan regulation through TORC1 signaling. Our findings suggest that the epigenetic control of BCAA metabolism, specifically through the modification of histone residues, contributes to maintaining metabolic homeostasis and replicative lifespan.</div></div>","PeriodicalId":342,"journal":{"name":"iScience","volume":"28 7","pages":"Article 112846"},"PeriodicalIF":4.6,"publicationDate":"2025-06-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144480903","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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
Genetic signatures in the highly virulent subtype B human immunodeficiency virus-1 conferring resistance to broadly neutralizing antibodies 高毒力乙型人类免疫缺陷病毒-1亚型的遗传特征赋予对广泛中和抗体的抗性
IF 4.6 2区 综合性期刊
iScience Pub Date : 2025-06-07 DOI: 10.1016/j.isci.2025.112847
Manukumar Honnayakanahalli Marichannegowda , Georgina Agyekum , Cinthya Zelaya Aparicio , Alonso Heredia , Yin Wang , Hongshuo Song
{"title":"Genetic signatures in the highly virulent subtype B human immunodeficiency virus-1 conferring resistance to broadly neutralizing antibodies","authors":"Manukumar Honnayakanahalli Marichannegowda ,&nbsp;Georgina Agyekum ,&nbsp;Cinthya Zelaya Aparicio ,&nbsp;Alonso Heredia ,&nbsp;Yin Wang ,&nbsp;Hongshuo Song","doi":"10.1016/j.isci.2025.112847","DOIUrl":"10.1016/j.isci.2025.112847","url":null,"abstract":"<div><div>HIV-1 is considered to become less sensitive to existing neutralizing antibodies over time. Our study on virulent B (VB) HIV-1 identified genetic signatures responsible for immune escape from broadly neutralizing antibodies (bNAbs) targeting V1/V2 and V3 epitopes. We found that the absence of the N295 and N332 glycans in the high mannose patch, which are crucial for neutralization by V3 glycan bNAbs and are typically conserved in subtype B HIV-1, is a notable feature in more than half of the VB variants. Neutralization assays confirmed that the loss of these two glycans in VB HIV-1 leads to escape from V3 glycan bNAbs. Additionally, all VB variants have an insertion in V2, contributing to escape from V1/V2 bNAbs PG9 and PG16. These findings demonstrate that the VB strains have unique genetic and neutralization characteristics compared to other subtype B strains. The evolutionary origin of these distinctive features remains to be determined.</div></div>","PeriodicalId":342,"journal":{"name":"iScience","volume":"28 7","pages":"Article 112847"},"PeriodicalIF":4.6,"publicationDate":"2025-06-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144314417","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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
Functional impact of the hyperduplication genomophenotype in high copy number endometrial cancer 高拷贝数子宫内膜癌中超重复基因表型的功能影响
IF 4.6 2区 综合性期刊
iScience Pub Date : 2025-06-07 DOI: 10.1016/j.isci.2025.112850
Angela Florio , James Smadbeck , Sarah H. Johnson , Wan-Hsin Lin , Dorsay Sadeghian , Sotiris Sotiriou , Rebeca Salvatori , Ryan W. Feathers , Taylor Berry , Lindsey Kinsella , Faye R. Harris , Alexa F. McCune , Stephen J. Murphy , Mohamed F. Ali , Abdulmohammad Pezeshki , Michael T. Barrett , Leah Grcevich , Ilaria Capasso , Luigi Antonio De Vitis , Gabriella Schivardi , George Vasmatzis
{"title":"Functional impact of the hyperduplication genomophenotype in high copy number endometrial cancer","authors":"Angela Florio ,&nbsp;James Smadbeck ,&nbsp;Sarah H. Johnson ,&nbsp;Wan-Hsin Lin ,&nbsp;Dorsay Sadeghian ,&nbsp;Sotiris Sotiriou ,&nbsp;Rebeca Salvatori ,&nbsp;Ryan W. Feathers ,&nbsp;Taylor Berry ,&nbsp;Lindsey Kinsella ,&nbsp;Faye R. Harris ,&nbsp;Alexa F. McCune ,&nbsp;Stephen J. Murphy ,&nbsp;Mohamed F. Ali ,&nbsp;Abdulmohammad Pezeshki ,&nbsp;Michael T. Barrett ,&nbsp;Leah Grcevich ,&nbsp;Ilaria Capasso ,&nbsp;Luigi Antonio De Vitis ,&nbsp;Gabriella Schivardi ,&nbsp;George Vasmatzis","doi":"10.1016/j.isci.2025.112850","DOIUrl":"10.1016/j.isci.2025.112850","url":null,"abstract":"<div><div>High copy-number endometrial cancers (HCNECs) are dominated by excessive duplications scattered across the genome, termed here as the hyperduplication genomophenotype (HDGP). We identified locations and sizes of duplications in 171 endometrial cancer cases and designated 71 HCNEC cases as HDGP. We also investigated the response to the pan-ERBB inhibitor afatinib in a subset of HDGP-EC cases with <em>ERBB2/ERBB3</em> duplications using a patient-derived three-dimensional culture model. Our analysis demonstrates that beyond tandem duplications there is a more general pattern involving coordinated duplication of multiple distant regions of the genome, demonstrating preferential selectivity to overexpressed potential oncogenes within a broad network. This suggests that HDGP increases tumor fitness and resistance to therapy by perturbing important gene networks in concert rather than only driver genes, suggesting a mechanistic basis for the ineffectiveness of targeted drugs in these patients and highlighting the need for combination therapies in these highly aggressive cases.</div></div>","PeriodicalId":342,"journal":{"name":"iScience","volume":"28 7","pages":"Article 112850"},"PeriodicalIF":4.6,"publicationDate":"2025-06-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144314351","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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
Molecular evolution and spatial transmission of Dabieshan tick virus in Jilin Province, northeastern China 吉林省大别山蜱病毒的分子进化与空间传播
IF 4.6 2区 综合性期刊
iScience Pub Date : 2025-06-07 DOI: 10.1016/j.isci.2025.112838
Ning Liu , Jingge Ma , Yu Liu , Yunzhi Peng , Ziyan Liu , Zheng Gui , Feng Wei , Liang Li , Bin Wang , Zedong Wang
{"title":"Molecular evolution and spatial transmission of Dabieshan tick virus in Jilin Province, northeastern China","authors":"Ning Liu ,&nbsp;Jingge Ma ,&nbsp;Yu Liu ,&nbsp;Yunzhi Peng ,&nbsp;Ziyan Liu ,&nbsp;Zheng Gui ,&nbsp;Feng Wei ,&nbsp;Liang Li ,&nbsp;Bin Wang ,&nbsp;Zedong Wang","doi":"10.1016/j.isci.2025.112838","DOIUrl":"10.1016/j.isci.2025.112838","url":null,"abstract":"<div><div>Dabieshan tick virus (DBTV), a tick-borne virus belonging to the genus <em>Uukuvirus</em> in the family Phenuiviridae, exhibits potential pathogenicity to humans and animals. However, its geographic distribution and transmission dynamics remain poorly understood. In this study, we analyzed 1,352 ticks collected from Jilin Province, China, revealing DBTV prevalence rates of 20.8% in <em>Haemaphysalis concinna</em> and 23.6% in <em>Haemaphysalis longicornis</em>. Additionally, nine recombination events and 14 reassortment events were identified, suggesting close evolutionary relationships between Jilin strains and those from Shandong and Hubei provinces. Bayesian phylodynamic analysis indicates that DBTV likely originated in Hubei 13–80 years ago, subsequently spreading to Shandong and then to Jilin. This study provides critical epidemiological evidence and insights into the genetic evolution of DBTV in northeastern China.</div></div>","PeriodicalId":342,"journal":{"name":"iScience","volume":"28 7","pages":"Article 112838"},"PeriodicalIF":4.6,"publicationDate":"2025-06-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144338631","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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
Protection of infant mice against pertussis, tuberculosis and influenza by co-administration of nasal pertussis vaccine candidate BPZE1 and BCG 鼻百日咳候选疫苗BPZE1和卡介苗联合接种对幼鼠百日咳、肺结核和流感的保护作用
IF 4.6 2区 综合性期刊
iScience Pub Date : 2025-06-07 DOI: 10.1016/j.isci.2025.112839
Carine Rouanet , Anne-Sophie Debrie , Stephane Cauchi , Nathalie Mielcarek
{"title":"Protection of infant mice against pertussis, tuberculosis and influenza by co-administration of nasal pertussis vaccine candidate BPZE1 and BCG","authors":"Carine Rouanet ,&nbsp;Anne-Sophie Debrie ,&nbsp;Stephane Cauchi ,&nbsp;Nathalie Mielcarek","doi":"10.1016/j.isci.2025.112839","DOIUrl":"10.1016/j.isci.2025.112839","url":null,"abstract":"<div><div>Protecting neonates at risk of serious pertussis disease or death represents a global emergency. BPZE1 is the most advanced, next-generation pertussis vaccine undergoing clinical evaluation in children and adults. We investigated the feasibility of co-administering BPZE1 and Bacillus Calmette-Guerin (BCG), the most widely used tuberculosis vaccine worldwide. We showed that BPZE1 can be co-administered with BCG without altering its immunogenicity and protective efficacy against <em>B. pertussis</em> in infant mice. Conversely, BCG immunogenicity and protective efficacy against <em>M. tuberculosis</em> are not affected by BPZE1. Both vaccines induce off-target protection against heterologous infections. In this study, we showed that BPZE1 and BCG alone or in combination induced high levels of protection against influenza challenge in infant mice. In contrast to BCG, the off-target properties of BPZE1 were independent of the age of vaccination. Vaccination with BPZE1 might be considered at the same time as BCG, facilitating its effective implementation in the childhood immunization schedule.</div></div>","PeriodicalId":342,"journal":{"name":"iScience","volume":"28 7","pages":"Article 112839"},"PeriodicalIF":4.6,"publicationDate":"2025-06-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144329819","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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
Serine synthesis pathway regulates cardiac differentiation from human pluripotent stem cells 丝氨酸合成途径调控人类多能干细胞的心脏分化
IF 4.6 2区 综合性期刊
iScience Pub Date : 2025-06-07 DOI: 10.1016/j.isci.2025.112843
Tomohiko C. Umei , Shugo Tohyama , Yuika Morita-Umei , Manami Katoh , Seitaro Nomura , Kotaro Haga , Takako Hishiki , Tomomi Matsuura , Hidenori Tani , Yusuke Soma , Otoya Sekine , Masatoshi Ohno , Masashi Nakamura , Taijun Moriwaki , Yoshikazu Kishino , Keiichi Fukuda , Masaki Ieda
{"title":"Serine synthesis pathway regulates cardiac differentiation from human pluripotent stem cells","authors":"Tomohiko C. Umei ,&nbsp;Shugo Tohyama ,&nbsp;Yuika Morita-Umei ,&nbsp;Manami Katoh ,&nbsp;Seitaro Nomura ,&nbsp;Kotaro Haga ,&nbsp;Takako Hishiki ,&nbsp;Tomomi Matsuura ,&nbsp;Hidenori Tani ,&nbsp;Yusuke Soma ,&nbsp;Otoya Sekine ,&nbsp;Masatoshi Ohno ,&nbsp;Masashi Nakamura ,&nbsp;Taijun Moriwaki ,&nbsp;Yoshikazu Kishino ,&nbsp;Keiichi Fukuda ,&nbsp;Masaki Ieda","doi":"10.1016/j.isci.2025.112843","DOIUrl":"10.1016/j.isci.2025.112843","url":null,"abstract":"<div><div>Human pluripotent stem cell-derived cardiomyocyte (hPSC-CM) differentiation can improve using chemical compounds which mimic early heart development. However, variations in hPSC-CM differentiation efficiency and its poor reproducibility have remained a challenge. Here, we report a unique metabolic method to promote hPSC-CM differentiation that involves marked suppression of the mitochondrial oxidative phosphorylation from the mesendoderm to the cardiac mesoderm, which is regulated by PHGDH, a rate-limiting enzyme in the serine synthesis pathway. Mechanistically, PHGDH inhibition impairs mitochondrial respiration by blocking the electron transport chain, resulting in elevated ROS levels and promoting the cardiomyocyte lineage specification by disrupting the cardiopharyngeal mesoderm lineage differentiation. Additionally, antioxidant supplementation can scavenge ROS and eliminate the effects of PHGDH inhibition. Collectively, our findings show that serine synthesis pathway can regulate cardiomyocyte lineage specification and have implications in providing a cellular source for transplantation and elucidating the potential mechanisms of heart development and pathogenesis of heart disease.</div></div>","PeriodicalId":342,"journal":{"name":"iScience","volume":"28 7","pages":"Article 112843"},"PeriodicalIF":4.6,"publicationDate":"2025-06-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144471417","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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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