{"title":"A long noncoding RNA with enhancer-like function in pig zygotic genome activation.","authors":"Renyue Wei, Yanbin Yue, Yinhuan Wu, Chenyuan Zhang, Jun-Xue Jin, Zhonghua Liu, Jiaqiang Wang","doi":"10.1093/jmcb/mjae061","DOIUrl":"10.1093/jmcb/mjae061","url":null,"abstract":"<p><p>The zygotic genome activation (ZGA) is crucial for the development of pre-implantation embryos. Long noncoding RNAs (lncRNAs) play significant roles in many biological processes, but the study on their role in the early embryonic development of pigs is limited. In this study, we identify lncFKBPL as an enhancer-type lncRNA essential for pig embryo development. lncFKBPL is expressed from the 4-cell stage to the morula stage in pig embryos, and interference with lncFKBPL leads to a developmental arrest at the 8-cell stage. Mechanistic investigations uncover that lncFKBPL is able to bind to MED8, thereby mediating enhancer activity and regulating FKBPL expression. Additionally, FKBPL interacts with the molecular chaperone protein HSP90AA1, stabilizing CDK9 and boosting its protein-level expression. Elevated CDK9 levels enhance Pol II phosphorylation, facilitating ZGA. Our findings illuminate the role of lncFKBPL as an enhancer lncRNA in pig ZGA regulation and early embryo development, providing a foundation for further exploration in this area.</p>","PeriodicalId":16433,"journal":{"name":"Journal of Molecular Cell Biology","volume":" ","pages":""},"PeriodicalIF":5.3,"publicationDate":"2025-06-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12210014/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142921672","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":"A look back at the Virology Departmental Days of the Institut Pasteur (Le Touquet, May 13-15, 2024).","authors":"Rubén González, Cassandra Koh, Bérangère Virlon, Sarah Hélène Merkling, Jean-Pierre Vartanian","doi":"10.1093/jmcb/mjae052","DOIUrl":"10.1093/jmcb/mjae052","url":null,"abstract":"","PeriodicalId":16433,"journal":{"name":"Journal of Molecular Cell Biology","volume":" ","pages":""},"PeriodicalIF":5.3,"publicationDate":"2025-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12159595/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143052692","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":"Application of nanomedicines in tumor immunotherapy.","authors":"Zirui Gao, Dandan Wan, Min Luo, Xiawei Wei","doi":"10.1093/jmcb/mjae055","DOIUrl":"10.1093/jmcb/mjae055","url":null,"abstract":"<p><p>Tumor immunotherapy has emerged as a formidable strategy, demonstrating substantial achievements in the field of cancer treatment. Despite its remarkable success, intrinsic limitations such as insufficient targeting capabilities, side effects, and resistance to immunotherapy hinder its efficacy. To address these challenges, the utilization of nanomedicines in tumor immunotherapy has been broadly explored, capitalizing on their advantages of targeting delivery capability, loading capacity, modifiability, and biocompatibility. Through rational design approaches, nanomedicines are engineered to meet diverse delivery requirements and synergize with different regimens to maximize therapeutic efficacy while alleviating side effects. This review initially discusses the challenges associated with tumor immunotherapy and underscores the pivotal role played by nanomedicines in overcoming these obstacles. Subsequently, representative types of nanoparticles are systematically introduced based on their structural properties, advantages, potential limitations, and future research directions. Special emphasis is placed on recent advancements in a range of nanomedicines designed for specific tumor immunotherapy strategies. Finally, the clinical applications as well as prospects of nanomedicines are discussed.</p>","PeriodicalId":16433,"journal":{"name":"Journal of Molecular Cell Biology","volume":" ","pages":""},"PeriodicalIF":5.3,"publicationDate":"2025-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12159600/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142895541","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}
Xiaohong Li, Yong Dong, Xu Pan, Wencui Sun, Yuan Xue, Ya Zhou, Mowen Lai, Yonggang Zhang, Feng Ma
{"title":"Early differentiation of committed erythroid cells defined by miR-144/451 expression.","authors":"Xiaohong Li, Yong Dong, Xu Pan, Wencui Sun, Yuan Xue, Ya Zhou, Mowen Lai, Yonggang Zhang, Feng Ma","doi":"10.1093/jmcb/mjae057","DOIUrl":"10.1093/jmcb/mjae057","url":null,"abstract":"<p><p>Before committing to an erythroid cell lineage, hematopoietic stem cells differentiate along a myeloid cell pathway to generate megakaryocyte-erythroid biopotential progenitor cells in bone marrow. Recent studies suggest that erythroid progenitors (EryPs) could be generated at the level of common myeloid progenitors (CMPs). However, due to a lack of suitable markers, little is known about the early differentiation of these committed EryP cells during CMP development. Herein, using miR-144/451-eGFP knock-in mice, we found that early differentiation of committed erythroid cells could be defined by miR-144/451 expression within CMPs. Single-cell RNA sequencing showed that miR-144/451+ progenitors show obvious differentiation characteristics of erythroid lineage cells and diverge from megakaryocyte and other myeloid cell lineages. These progenitors exclusively give rise to erythroid cells, both in vitro and in vivo, and the commitment to an erythroid cell lineage is accompanied by loss of CD53 expression. Our findings will facilitate further understanding of the molecular mechanisms governing erythroid development and support the identification of therapeutic targets for diseases related to erythrocyte development.</p>","PeriodicalId":16433,"journal":{"name":"Journal of Molecular Cell Biology","volume":" ","pages":""},"PeriodicalIF":5.3,"publicationDate":"2025-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12159597/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142950265","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":"GPI transamidase complex is required for primordial germ cell migration and development in zebrafish.","authors":"Weiying Zhang, Yaqi Li, Jing Chen, Likun Yao, Bingjie Zhang, Lin Zhang, Boqi Liu, Weimin Shen, Anming Meng, Xiaotong Wu","doi":"10.1093/jmcb/mjae058","DOIUrl":"10.1093/jmcb/mjae058","url":null,"abstract":"<p><p>Proteins without transmembrane domains could be anchored to the cell surface for regulating various biological processes when covalently linked to glycosylphosphatidylinositol (GPI) molecules by the GPI transamidase (GPIT) complex. However, it remains poorly understood whether and how the GPIT complex affects primordial germ cell (PGC) development. In this study, we report the important roles of the GPIT complex in PGC migration and development in zebrafish embryos. Mutation of pigu or pigk, both encoding essential GPIT complex subunits, resulted in defective PGC migration with ectopically located PGCs and reduction of PGC counts. Notably, a detailed analysis of filopodia in PGCs revealed the attenuated polarity of filopodia distribution along the migration direction in mutant embryos. PGC transplantation and PGC-specific rescue experiments demonstrated that both PGC and somatic cell-expressed Pigu are required for PGC migration. Furthermore, expression levels of PGC-specific genes decreased in pigu mutant PGCs with the derepression of somatic cell genes. Hence, we propose that the GPIT complex plays a critical role during PGC migration and development.</p>","PeriodicalId":16433,"journal":{"name":"Journal of Molecular Cell Biology","volume":" ","pages":""},"PeriodicalIF":5.3,"publicationDate":"2025-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12159598/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142914966","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}
Feng-Ran Xiong, Juan-Juan Zhu, Xiao-Rong Zhu, Jing Lu, Jin-Kui Yang
{"title":"Low-dose quinine targets KCNH6 to potentiate glucose-induced insulin secretion.","authors":"Feng-Ran Xiong, Juan-Juan Zhu, Xiao-Rong Zhu, Jing Lu, Jin-Kui Yang","doi":"10.1093/jmcb/mjae051","DOIUrl":"10.1093/jmcb/mjae051","url":null,"abstract":"<p><p>Insulin secretion is mainly regulated by two electrophysiological events, depolarization initiated by the closure of adenosine triphosphate (ATP)-sensitive K+ (KATP) channels and repolarization mediated by K+ efflux. Quinine, a natural component commonly used for the treatment of malaria, has been reported to directly stimulate insulin release and lead to hypoglycemia in patients during treatment through inhibiting KATP channels. In this study, we verified the insulinotropic effect of quinine on the isolated mouse pancreatic islets. We also revealed that low-dose quinine (<20 μM) did not directly provoke Ca2+ spikes or insulin secretion under low-glucose conditions but potentiated Ca2+ influx and insulin secretion induced by high glucose, which cannot be explained by KATP inhibition. KCNH6 (hERG2) is a voltage-dependent K+ (Kv) channel that plays a critical role in the repolarization of pancreatic β cells. Patch clamp experiments showed that quinine inhibited hERG channels at low micromolar concentrations. However, whether quinine can target KCNH6 to potentiate glucose-induced insulin secretion remains unclear. Here, we showed that in vivo administration of low-dose quinine (25 mg/kg) improved glucose tolerance and increased glucose-induced insulin release in wild-type control mice but not in Kcnh6-β-cell-specific knockout (βKO) mice. Consistently, in vitro treatment of primary islet β cells with low-dose quinine (10 μM) prolonged action potential duration and augmented glucose-induced Ca2+ influx in the wild-type control group but not in the Kcnh6-βKO group. Our results demonstrate that KCNH6 plays an important role in low-dose quinine-potentiated insulin secretion and provide new insights into KCNH6-targeted drug development.</p>","PeriodicalId":16433,"journal":{"name":"Journal of Molecular Cell Biology","volume":" ","pages":""},"PeriodicalIF":5.3,"publicationDate":"2025-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12120441/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143029093","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}
Yaqi Yang, Jiejun Wen, Susu Lou, Yali Han, Yi Pan, Ying Zhong, Qiao He, Yinfeng Zhang, Xi Mo, Jing Ma, Nan Shen
{"title":"DNAJC12 downregulation induces neuroblastoma progression via increased histone H4K5 lactylation.","authors":"Yaqi Yang, Jiejun Wen, Susu Lou, Yali Han, Yi Pan, Ying Zhong, Qiao He, Yinfeng Zhang, Xi Mo, Jing Ma, Nan Shen","doi":"10.1093/jmcb/mjae056","DOIUrl":"10.1093/jmcb/mjae056","url":null,"abstract":"<p><p>Neuroblastoma (NB) is the most common extracranial solid tumor in children. Despite treatment advances, the survival rates of high-risk NB patients remain low. This highlights the urgent need for a deeper understanding of the molecular mechanisms driving NB progression to support the development of new therapeutic strategies. In this study, we demonstrated that the reduced levels of DNAJC12, a protein involved in metabolic regulation, are associated with poor prognosis in NB patients. Our data indicate that low DNAJC12 expression activates glycolysis in NB cells, leading to increased lactic acid production and histone H4 lysine 5 lactylation (H4K5la). Elevated H4K5la upregulates the transcription of COL1A1, a gene implicated in cell metastasis. Immunohistochemistry staining of NB patient samples confirmed that high H4K5la levels correlate with poor clinical outcomes. Furthermore, we showed that inhibiting glycolysis, reducing H4K5la, or targeting COL1A1 can mitigate the invasive behavior of NB cells. These findings reveal a critical link between metabolic reprogramming and epigenetic modifications in the context of NB progression, suggesting that H4K5la could serve as a novel diagnostic and prognostic marker, and shed light on identifying new therapeutic targets within metabolic pathways for the treatment of this aggressive pediatric cancer.</p>","PeriodicalId":16433,"journal":{"name":"Journal of Molecular Cell Biology","volume":" ","pages":""},"PeriodicalIF":5.3,"publicationDate":"2025-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12096081/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142882331","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}