{"title":"Mechanism and application of lactylation in cancers.","authors":"Jiewen Wang, Mingjing Peng, Linda Oyang, Mengzhou Shen, Shizhen Li, Xianjie Jiang, Zongyao Ren, Qiu Peng, Xuemeng Xu, Shiming Tan, Longzheng Xia, Wenjuan Yang, Haofan Li, Nayiyuan Wu, Yanyan Tang, Jinguan Lin, Qianjin Liao, Yaqian Han, Yujuan Zhou","doi":"10.1186/s13578-025-01415-9","DOIUrl":"10.1186/s13578-025-01415-9","url":null,"abstract":"<p><p>Lactate is a crucial product of cancer metabolism, creating an acidic environment that supports cancer growth and acts as a substrate for lactylation. Lactylation, a newly discovered epigenetic modification, plays a vital role in cancer cell signaling, metabolic reprogramming, immune response, and other functions. This review explores the regulation of lactylation, summarizes recent research on its role in cancers, and highlights its application in cancer drug resistance and immunotherapy. These insights aim to provide new avenues for targeting lactylation in cancer therapy.</p>","PeriodicalId":49095,"journal":{"name":"Cell and Bioscience","volume":"15 1","pages":"76"},"PeriodicalIF":6.1,"publicationDate":"2025-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12135226/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144227313","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Yifeng Gao, Qing Yin, Yaser Gamallat, Michael G Grant, Aidan H Snell, Xingxing Shi, Lara N Ulstad, Arshita Singh, Tingan Chen, Joseph O Johnson, Dorina Avram, Lixin Wan
{"title":"Linear ubiquitination of p31<sup>comet</sup> by HOIP couples cytokine response with mitotic regulation.","authors":"Yifeng Gao, Qing Yin, Yaser Gamallat, Michael G Grant, Aidan H Snell, Xingxing Shi, Lara N Ulstad, Arshita Singh, Tingan Chen, Joseph O Johnson, Dorina Avram, Lixin Wan","doi":"10.1186/s13578-025-01416-8","DOIUrl":"10.1186/s13578-025-01416-8","url":null,"abstract":"<p><strong>Background: </strong>Inflammation and genomic instability are among the hallmarks of human cancer. Proinflammatory cytokines induce DNA damage through the accumulation of reactive oxygen and nitrogen species (RONS), which often leads to base alternations. The link between proinflammatory cytokines and chromosomal instability remains largely elusive.</p><p><strong>Results: </strong>Here, we report that the mitotic checkpoint protein p31<sup>comet</sup> (MAD2L1BP) is modified by linear ubiquitination via the E3 ubiquitin ligase HOIP after cytokine stimulation. HOIP-mediated polyubiquitination of p31<sup>comet</sup> occurs on its C-terminal lysine residues. Ubiquitinated p31<sup>comet</sup> displays reduced binding to PLK1, which phosphorylates and inactivates p31<sup>comet</sup>. Thus HOIP positively regulates p31<sup>comet</sup> function. Consistent with this notion, HOIP-deficient cells exhibit prolonged mitotic duration similar to p31<sup>comet</sup> knockout. Mitotic defects are also more prevalent in cells without HOIP or p31<sup>comet</sup>. Moreover, compared with the cells expressing wild-type p31<sup>comet</sup>, cells expressing a ubiquitination-deficient p31<sup>comet</sup> mutant take more time to complete the M phase.</p><p><strong>Conclusions: </strong>Our results together uncover a mechanistic link between the proinflammatory cytokines and the mitotic checkpoint pathways. This molecular switch could be explored as a potential therapeutic target in inflammation-driving or p31<sup>comet</sup> overexpressed cancer types.</p>","PeriodicalId":49095,"journal":{"name":"Cell and Bioscience","volume":"15 1","pages":"75"},"PeriodicalIF":6.1,"publicationDate":"2025-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12135451/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144217380","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Xiao Han, Keliang Pang, Xiaohui Liu, Jun Zhou, Jun Zhu, Hao Yuan
{"title":"Novel roles for CREG1 in hematopoiesis revealed by single-cell RNA sequencing.","authors":"Xiao Han, Keliang Pang, Xiaohui Liu, Jun Zhou, Jun Zhu, Hao Yuan","doi":"10.1186/s13578-025-01407-9","DOIUrl":"10.1186/s13578-025-01407-9","url":null,"abstract":"<p><strong>Background: </strong>Hematopoiesis, the process of generating diverse blood cell lineages, is essential for maintaining organismal homeostasis and survival. CREG1 has been implicated in various cellular processes, including proliferation, differentiation, and senescence. However, its role in adult hematopoiesis and the development of specific blood cell lineages remains largely unknown.</p><p><strong>Results: </strong>In this study, we utilized single-cell RNA sequencing (scRNA-seq) to investigate the function of CREG1 in hematopoietic development in adult zebrafish. Our analysis revealed significant alterations in cellular composition and gene expression profiles in kidney marrow of creg1-deficient zebrafish, particularly affecting B cell, T/NK cell, and erythroid cell development. The loss of CREG1 led to impaired endocytosis and lysosomal activity in lymphocytes, and inhibited differentiation of classical erythroid cells while promoting the development of immune-associated erythroid cells. These findings highlight a critical role for CREG1 in regulating hematopoietic lineage development, potentially through modulation of cell survival, endocytosis, and lysosomal function.</p><p><strong>Conclusions: </strong>Our study expands the current understanding of CREG1's role in hematopoiesis and provides a foundation for future investigations into the specific molecular mechanisms by which CREG1 regulates hematopoietic lineage development and function.</p>","PeriodicalId":49095,"journal":{"name":"Cell and Bioscience","volume":"15 1","pages":"74"},"PeriodicalIF":6.1,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12128286/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144200597","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Zhuran Zhao, Xi Chen, Shan Wang, Min Fu, Huan Shen, Jiayu Li, Jun Xu, Jiong Qin, Cheng Shi
{"title":"Chemically defined and xeno-free media enables the derivation of human extended pluripotent stem cell lines from discarded blastocysts with a high efficiency.","authors":"Zhuran Zhao, Xi Chen, Shan Wang, Min Fu, Huan Shen, Jiayu Li, Jun Xu, Jiong Qin, Cheng Shi","doi":"10.1186/s13578-025-01410-0","DOIUrl":"10.1186/s13578-025-01410-0","url":null,"abstract":"","PeriodicalId":49095,"journal":{"name":"Cell and Bioscience","volume":"15 1","pages":"72"},"PeriodicalIF":6.1,"publicationDate":"2025-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12123846/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144188345","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Hippocampal CA1 neuron, a crucial regulator for chronic stress exacerbating Alzheimer's disease progression.","authors":"Qing-Lin Gao, Hai-Wei Zha, Zi-Jie Liu, Miao-Miao Wang, Yu-Qing Zhang, Jia-Rui Bi, Tian-Yang Wu, Zhen-Jiang Liu, Hui Wu, Dong Sun","doi":"10.1186/s13578-025-01420-y","DOIUrl":"10.1186/s13578-025-01420-y","url":null,"abstract":"<p><p>Chronic stress, a common risk factor for psychiatric disorders, is also implicated in the pathogenesis of Alzheimer's disease (AD). However, its underlying mechanisms remain elusive. Here, we provide evidence for chronic restraint stress (CRS), a widely used stress model in rodents, to regulate AD pathology. CRS not only induces prolonged depressive-like behaviors and cognitive deficits in young adult wild type (WT) mice, but also exacerbates a series of AD-related phenotypes in APP/PS1 mice, including impaired spatial learning and memory, increased β-amyloid plaques, promoted glial cells (astrocyte and microglial cell) activation and decreased dendritic spines in CA1 neurons. Single-nucleus RNA-sequencing analysis in hippocampus shows remarkable transcriptional changes in many cell type(s), and identifies oxidative phosphorylation pathway, a major source for adenosine triphosphate (ATP) production, is significantly downregulated in CA1 neurons by CRS stimuli. Furthermore, dysfunctional mitochondria and reduced ATP levels are also observed in CA1 neurons of CRS exposed WT and APP/PS1 mice. Interestingly, infusion of ATP in CA1 region abolishes the deficits in cognition, dendritic spines and glial activation in CRS exposed APP/PS1 mice. Taken together, these results uncover an unrecognized function of CA1 neurons in regulating CRS induced AD pathologies, and suggest ATP as a promising therapeutic strategy to improve brain health under stress condition.</p>","PeriodicalId":49095,"journal":{"name":"Cell and Bioscience","volume":"15 1","pages":"73"},"PeriodicalIF":6.1,"publicationDate":"2025-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12125776/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144188346","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Shedding light on the cell biology and diverse physiological functions of the migrasome.","authors":"Yuxing Huang, Yi Huang, Jian Gao","doi":"10.1186/s13578-025-01417-7","DOIUrl":"10.1186/s13578-025-01417-7","url":null,"abstract":"<p><p>The migrasome, an organelle that forms behind migrating cells, is connected to the cell body by a retraction fiber. Once released from the retraction fiber, the migrasome transforms into an extracellular vesicle and plays important roles in cell communication, development, angiogenesis, and disease. To date, the biogenesis, regulation of formation, cargo transportation, and physiological functions of migrasomes remain largely unknown. In this review, we summarize the current understanding of the mechanisms underlying migrasome formation and regulation, describe the evidence suggesting that migrasomes serve various physiological functions, compare the differences between migrasomes and other extracellular vesicles, emphasize the limitations in studying migrasomes, and discuss the potential of migrasomes in disease diagnosis and treatment.</p>","PeriodicalId":49095,"journal":{"name":"Cell and Bioscience","volume":"15 1","pages":"70"},"PeriodicalIF":6.1,"publicationDate":"2025-05-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12121079/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144175139","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Emerging roles of ribosome translation in stem cells and stem cell therapy - a review.","authors":"Yanyan Gao, Linlin Guo, Gaoxiang Shi, Ruifang Wang, Xu'an Wang, Jizhong Lou","doi":"10.1186/s13578-025-01412-y","DOIUrl":"10.1186/s13578-025-01412-y","url":null,"abstract":"<p><p>Stem cells differ from other somatic cells in that they possess self-renewal and differentiation potential, which endows them with unique characteristics, and have great therapeutic potential. Studies have shown that the self-renewal and differentiation potential of stem cells is regulated by ribosomes during protein synthesis. In this review, we discuss the translation regulation mechanisms and ribosome biogenesis in stem cells. Protein translation levels and ribosome biogenesis change dynamically during the development and differentiation of stem cells, and hierarchical translational regulation promotes stem cell differentiation. We also demonstrate that mitochondrial protein translation plays an important role in the regulation of stem cell fate. Ribosomes not only mediate the self-renewal and differentiation of stem cells through protein synthesis. They are also a key target for stem cell therapy. Understanding the mechanism of ribosome regulation in stem cells will allow better control of stem cells for their application.</p>","PeriodicalId":49095,"journal":{"name":"Cell and Bioscience","volume":"15 1","pages":"71"},"PeriodicalIF":6.1,"publicationDate":"2025-05-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12121016/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144174907","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Rab11a-dependent recycling of Glut3 inhibits seizure-induced neuronal disulfidptosis by alleviating glucose deficiency.","authors":"Sijun Li, Junrui He, Huimin Kuang, Xiaojuan Wang, Muhua Zhou, Dongmei Li, Baoren Kang, Honghu He, Lina He, Wei Lin, Yuan Lv","doi":"10.1186/s13578-025-01396-9","DOIUrl":"10.1186/s13578-025-01396-9","url":null,"abstract":"<p><p>Seizures can trigger neuronal glucose deficiency, thereby inducing disulfidptosis. Disulfidptosis is a novel cell death mechanism characterized by the abnormal accumulation of disulfide caused by glucose deficiency. However, the mechanism underlying disulfidptosis caused by glucose deficiency in seizures remains elusive. Rab11a-dependent recycling of glucose transporter 3 (Glut3) is closely related to glucose metabolism in neurons, which may contribute to neuronal disulfidptosis after seizures by abnormal glucose metabolism. So here we introduced a well-established in vitro model of seizures to evaluate cell survival, glucose levels, disulfidptosis biomarkers, Glut3 and Rab11a expression, the recycling ratio of Glut3, and the protein complex of Glut3-Rab11a. Cell survival rates and glucose levels were lower in the in vitro model of seizures, accompanied by elevated levels of disulfidptosis markers. Moreover, the surface expression and the recycling ratio of Glut3, as well as the protein complex of Glut3-Rab11a, were positively correlated with Rab11a expression. Lastly, Rab11 overexpression improved cell survival rates, increased glucose levels, and decreased the levels of disulfidptosis biomarkers in the in vitro model of seizure. Rab11a-dependent recycling of Glut3 inhibited seizure-induced neuronal disulfidptosis by alleviating glucose deficiency.</p>","PeriodicalId":49095,"journal":{"name":"Cell and Bioscience","volume":"15 1","pages":"69"},"PeriodicalIF":6.1,"publicationDate":"2025-05-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12121293/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144175208","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Junli Zhang, Xinxin Jin, Yachao Hou, Biao Gu, Hongwei Li, Li Yi, Wenjuan Wu, Shangshang Hu
{"title":"Comprehensive analysis of the critical role of the epithelial mesenchymal transition subtype - TAGLN-positive fibroblasts in colorectal cancer progression and immunosuppression.","authors":"Junli Zhang, Xinxin Jin, Yachao Hou, Biao Gu, Hongwei Li, Li Yi, Wenjuan Wu, Shangshang Hu","doi":"10.1186/s13578-025-01405-x","DOIUrl":"10.1186/s13578-025-01405-x","url":null,"abstract":"<p><p>Epithelial-mesenchymal transition (EMT) plays a pivotal role in tumor metastasis and immune suppression in colorectal cancer (CRC). However, the specific mechanisms of EMT and its relationship with the clinical prognosis and immunotherapy response in CRC patients remain unclear. In this study, we identified TAGLN-positive fibroblasts (TAGLN⁺Fib) as a cancer-associated fibroblast (CAF) subtype within the tumor microenvironment (TME) that promotes tumor metastasis and immune evasion. High EMT scores, strongly associated with TAGLN expression, were correlated with advanced tumor stages, poor prognosis, and resistance to immunotherapy. Functional experiments demonstrated that TAGLN knockdown significantly reduced CRC cell proliferation, migration, and EMT phenotypes in vitro and suppressed tumor growth in vivo. Furthermore, TAGLN⁺Fib closely interacted with MMP7-positive tumor epithelial cells and SPP1-positive macrophages, forming a pro-metastatic and immunosuppressive network. An EMT-TME risk model constructed using TAGLN⁺Fib exhibited robust predictive power for CRC prognosis and immunotherapy response. This study reveals the association of EMT scores with CRC prognosis and immunotherapy response, highlights TAGLN⁺Fib's critical role in tumor progression, and develops an EMT-TME risk model, offering insights for personalized CRC treatment and precision medicine.</p>","PeriodicalId":49095,"journal":{"name":"Cell and Bioscience","volume":"15 1","pages":"66"},"PeriodicalIF":6.1,"publicationDate":"2025-05-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12102804/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144144205","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Romane Gaston-Breton, Clémence Disdier, Henrik Hagberg, Aloïse Mabondzo
{"title":"Hypoxia-ischemia and sexual dimorphism: modeling mitochondrial dysfunction using brain organoids.","authors":"Romane Gaston-Breton, Clémence Disdier, Henrik Hagberg, Aloïse Mabondzo","doi":"10.1186/s13578-025-01402-0","DOIUrl":"10.1186/s13578-025-01402-0","url":null,"abstract":"<p><p>Hypoxic-ischemic encephalopathy (HIE) is a leading cause of neurodevelopmental morbidities in full-term infants. There is strong evidence of sexual differences in hypoxic-ischemic (HI) injury where male neonates are at higher risk as they are subject to more pronounced neurological deficits and death than females. The cellular and molecular mechanisms underlying these sexual discrepancies in HI injury are poorly understood. Mitochondrial dysregulation has been increasingly explored in brain diseases and represents a major target during HI events. In this review, we discuss (1) different mitochondrial functions in the central nervous system (2), mitochondrial dysregulation in the context of HI injury (3), sex-dependent mitochondrial pathways in HIE and (4) modeling of mitochondrial dysfunction using human brain organoids. Gaining insight into these novel aspects of mitochondrial function will offer valuable understanding of brain development and neurological disorders such as HI injury, paving the way for the discovery and creation of new treatment approaches.</p>","PeriodicalId":49095,"journal":{"name":"Cell and Bioscience","volume":"15 1","pages":"67"},"PeriodicalIF":6.1,"publicationDate":"2025-05-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12103005/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144144206","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}