Life medicinePub Date : 2024-11-13eCollection Date: 2024-12-01DOI: 10.1093/lifemedi/lnae038
Peng Xie, Shiqi Zhu, Jin Zhang, Xinrui Wang, Xu Jiang, Feng Xiong, Linjin Chen, Ke Fang, Yuanhui Ji, Beihong Zheng, Lincui Da, Hua Cao, Yan Sun, Zhuojuan Luo, Chengqi Lin
{"title":"4D live tracing reveals distinct movement trajectories of meiotic chromosomes.","authors":"Peng Xie, Shiqi Zhu, Jin Zhang, Xinrui Wang, Xu Jiang, Feng Xiong, Linjin Chen, Ke Fang, Yuanhui Ji, Beihong Zheng, Lincui Da, Hua Cao, Yan Sun, Zhuojuan Luo, Chengqi Lin","doi":"10.1093/lifemedi/lnae038","DOIUrl":"10.1093/lifemedi/lnae038","url":null,"abstract":"<p><p>Proper chromosome alignment at the spindle equator is a prerequisite for accurate chromosome segregation during cell division. However, the chromosome movement trajectories prior to alignment remain elusive. Here, we established a 4D imaging analysis framework to visualize chromosome dynamics and develop a deep-learning model for chromosome movement trajectory classification. Our data reveal that chromosomes follow at least three distinct movement trajectories (retracing, congressing, and quasi-static) to arrive at the equator. We further revealed the distinct roles of multiple kinesin superfamily proteins (KIFs) in coordinating and maintaining the chromosome movement trajectories. In summary, we have presented an efficient and unbiased approach to studying chromosome dynamics during cell division, thereby uncovering a variety of chromosome movement trajectories that precede alignment.</p>","PeriodicalId":74073,"journal":{"name":"Life medicine","volume":"3 6","pages":"lnae038"},"PeriodicalIF":0.0,"publicationDate":"2024-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11748274/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143054595","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Life medicinePub Date : 2024-10-21eCollection Date: 2024-10-01DOI: 10.1093/lifemedi/lnae036
Ping Zhou, Dan Mo, Hanji Huang, Jiaqi Xu, Baoying Liao, Yinxue Wang, Di Mao, Zhonghong Zeng, Ziying Huang, Chao Zhang, Yihua Yang, Yang Yu, Heng Pan, Rong Li
{"title":"Integrated transcriptomic analysis reveals dysregulated immune infiltration and pro-inflammatory cytokines in the secretory endometrium of recurrent implantation failure patients.","authors":"Ping Zhou, Dan Mo, Hanji Huang, Jiaqi Xu, Baoying Liao, Yinxue Wang, Di Mao, Zhonghong Zeng, Ziying Huang, Chao Zhang, Yihua Yang, Yang Yu, Heng Pan, Rong Li","doi":"10.1093/lifemedi/lnae036","DOIUrl":"10.1093/lifemedi/lnae036","url":null,"abstract":"<p><p>Recurrent implantation failure (RIF) is a leading impediment to assisted reproductive technology, yet the underlying pathogenesis of RIF remains elusive. Recent studies have sought to uncover novel biomarkers and etiological factors of RIF by profiling transcriptomes of endometrial samples. Nonetheless, the inherent heterogeneity among published studies and a scarcity of experimental validations hinder the identification of robust markers of RIF. Hence, we integrated six publicly accessible datasets with 209 samples, including microarray profiles of endometrial samples in the secretory phase. After removing batch effects, we identified 175 differentially expressed genes. Gene set enrichment analysis identified dysregulation of immunological pathways in RIF. We also observed altered immune infiltration and pro-inflammatory cytokines in RIF. Protein-protein interaction network analysis identified ten hub genes, representing two co-expression modules significantly related to RIF. Knockdown of <i>ENTPD3</i>, one of the hub genes, promoted the epithelial-mesenchymal transition process and resulted in elevated levels of pro-inflammatory cytokines. Collectively, our study reveals abnormal gene expressions involving the regulation of epithelial-mesenchymal transition and immune status in RIF, providing valuable insights into its pathogenesis.</p>","PeriodicalId":74073,"journal":{"name":"Life medicine","volume":"3 5","pages":"lnae036"},"PeriodicalIF":0.0,"publicationDate":"2024-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11749484/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143054565","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Life medicinePub Date : 2024-10-03eCollection Date: 2024-10-01DOI: 10.1093/lifemedi/lnae037
Hang Zhang, Yuan Chang, Jiangping Song
{"title":"Xenotransplantation: How close are we to clinical applications?","authors":"Hang Zhang, Yuan Chang, Jiangping Song","doi":"10.1093/lifemedi/lnae037","DOIUrl":"10.1093/lifemedi/lnae037","url":null,"abstract":"","PeriodicalId":74073,"journal":{"name":"Life medicine","volume":"3 5","pages":"lnae037"},"PeriodicalIF":0.0,"publicationDate":"2024-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11749621/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143054590","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Life medicinePub Date : 2024-09-13eCollection Date: 2024-08-01DOI: 10.1093/lifemedi/lnae034
Jing Guo, Lie Wang
{"title":"The complex landscape of immune dysregulation in multisystem inflammatory syndrome in children with COVID-19.","authors":"Jing Guo, Lie Wang","doi":"10.1093/lifemedi/lnae034","DOIUrl":"10.1093/lifemedi/lnae034","url":null,"abstract":"<p><p>The immune responses following SARS-CoV-2 infection in children are still under investigation. While coronavirus disease 2019 (COVID-19) is usually mild in the paediatric population, some children develop severe clinical manifestations or multisystem inflammatory syndrome in children (MIS-C) after infection. MIS-C, typically emerging 2-6 weeks after SARS-CoV-2 exposure, is characterized by a hyperinflammatory response affecting multiple organs. This review aims to explore the complex landscape of immune dysregulation in MIS-C, focusing on innate, T cell-, and B cell-mediated immunity, and discusses the role of SARS-CoV-2 spike protein as a superantigen in MIS-C pathophysiology. Understanding these mechanisms is crucial for improving the management and outcomes for affected children.</p>","PeriodicalId":74073,"journal":{"name":"Life medicine","volume":"3 4","pages":"lnae034"},"PeriodicalIF":0.0,"publicationDate":"2024-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11749780/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143054639","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Life medicinePub Date : 2024-09-06eCollection Date: 2024-08-01DOI: 10.1093/lifemedi/lnae032
Li Zhang, Taylor M Weiskittel, Yuqing Zhu, Dixuan Xue, Hailing Zhang, Yuxuan Shen, Hua Yu, Jingyu Li, Linxiao Hou, Hongshan Guo, Zhijun Dai, Hu Li, Jin Zhang
{"title":"Comparative dissection of transcriptional landscapes of human iPSC-NK differentiation and NK cell development.","authors":"Li Zhang, Taylor M Weiskittel, Yuqing Zhu, Dixuan Xue, Hailing Zhang, Yuxuan Shen, Hua Yu, Jingyu Li, Linxiao Hou, Hongshan Guo, Zhijun Dai, Hu Li, Jin Zhang","doi":"10.1093/lifemedi/lnae032","DOIUrl":"10.1093/lifemedi/lnae032","url":null,"abstract":"<p><p>Clinical and preclinical research has demonstrated that iPSC-derived NK (iNK) cells have a high therapeutic potential, yet poor understanding of the detailed process of their differentiation <i>in vitro</i> and their counterpart cell development <i>in vivo</i> has hindered therapeutic iNK cell production and engineering. Here we dissect the crucial differentiation of both fetal liver NK cells and iNK cells to enable the rational design of advanced iNK production protocols. We use a comparative analysis of single-cell RNA-seq (scRNA-seq) to pinpoint key factors lacking in the induced setting which we hypothesized would hinder iNK differentiation and/ or functionality. By analyzing key transcription factor regulatory networks, we discovered the importance of <i>TBX21</i>, <i>EOMES</i>, and <i>STAT5A</i> in the differentiation timeline. This analysis provides a blueprint for further engineering new iPSC lines to obtain iNK cells with enhanced functions. We validated this approach by creating a new line of STAT5A-iPSCs which can be differentiated to STAT5A-expressing macrophages with both NK cell and macrophage features such as perforin production, phagocytosis, and anti-tumor functions.</p>","PeriodicalId":74073,"journal":{"name":"Life medicine","volume":"3 4","pages":"lnae032"},"PeriodicalIF":0.0,"publicationDate":"2024-09-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11749552/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143054628","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Life medicinePub Date : 2024-09-05eCollection Date: 2024-10-01DOI: 10.1093/lifemedi/lnae033
Canwei Zhang, Zesong Lin, Yankun Yu, Siqi Wu, Huaxing Huang, Ying Huang, Jiafeng Liu, Kunlun Mo, Jieying Tan, Zhuo Han, Mingsen Li, Wei Zhao, Hong Ouyang, Xiangjun Chen, Li Wang
{"title":"Deciphering the dynamic single-cell transcriptional landscape in the ocular surface ectoderm differentiation system.","authors":"Canwei Zhang, Zesong Lin, Yankun Yu, Siqi Wu, Huaxing Huang, Ying Huang, Jiafeng Liu, Kunlun Mo, Jieying Tan, Zhuo Han, Mingsen Li, Wei Zhao, Hong Ouyang, Xiangjun Chen, Li Wang","doi":"10.1093/lifemedi/lnae033","DOIUrl":"10.1093/lifemedi/lnae033","url":null,"abstract":"<p><p>The ocular surface ectoderm (OSE) is essential for the development of the ocular surface, yet the molecular mechanisms driving its differentiation are not fully understood. In this study, we used single-cell transcriptomic analysis to explore the dynamic cellular trajectories and regulatory networks during the <i>in vitro</i> differentiation of embryonic stem cells (ESCs) into the OSE lineage. We identified nine distinct cell subpopulations undergoing differentiation along three main developmental branches: neural crest, neuroectodermal, and surface ectodermal lineages. Key marker gene expression, transcription factor activity, and signaling pathway insights revealed stepwise transitions from undifferentiated ESCs to fate-specified cell types, including a PAX6 + TP63 + population indicative of OSE precursors. Comparative analysis with mouse embryonic development confirmed the model's accuracy in mimicking <i>in vivo</i> epiblast-to-surface ectoderm dynamics. By integrating temporal dynamics of transcription factor activation and cell-cell communication, we constructed a comprehensive molecular atlas of the differentiation pathway from ESCs to distinct ectodermal lineages. This study provides new insights into the cellular heterogeneity and regulatory mechanisms of OSE development, aiding the understanding of ocular surface biology and the design of cell-based therapies for ocular surface disorders.</p>","PeriodicalId":74073,"journal":{"name":"Life medicine","volume":"3 5","pages":"lnae033"},"PeriodicalIF":0.0,"publicationDate":"2024-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11749776/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143054647","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Life medicinePub Date : 2024-08-31eCollection Date: 2024-08-01DOI: 10.1093/lifemedi/lnae030
Lin Sun, Zhensheng Yue, Lin Wang
{"title":"Research on the function of epigenetic regulation in the inflammation of non-alcoholic fatty liver disease.","authors":"Lin Sun, Zhensheng Yue, Lin Wang","doi":"10.1093/lifemedi/lnae030","DOIUrl":"10.1093/lifemedi/lnae030","url":null,"abstract":"<p><p>Nonalcoholic fatty liver disease (NAFLD) is the most prevalent chronic liver condition, characterized by a spectrum that progresses from simple hepatic steatosis to nonalcoholic steatohepatitis, which may eventually lead to cirrhosis and hepatocellular carcinoma. The precise pathogenic mechanisms underlying NAFLD and its related metabolic disturbances remain elusive. Epigenetic modifications, which entail stable transcriptional changes without altering the DNA sequence, are increasingly recognized as pivotal. The principal forms of epigenetic modifications include DNA methylation, histone modifications, chromatin remodeling, and noncoding RNAs. These alterations participate in the regulation of hepatic lipid metabolism, insulin resistance, mitochondrial injury, oxidative stress response, and release of inflammatory cytokines, all of which are associated with the onset and progression of NAFLD. This review discussed recent advances in understanding the potential epigenetic regulation of inflammation in NAFLD. Unraveling these epigenetic mechanisms may facilitate the identification of early diagnostic biomarkers and the development of targeted therapeutic strategies for NAFLD.</p>","PeriodicalId":74073,"journal":{"name":"Life medicine","volume":"3 4","pages":"lnae030"},"PeriodicalIF":0.0,"publicationDate":"2024-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11749620/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143054636","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Life medicinePub Date : 2024-08-29eCollection Date: 2024-08-01DOI: 10.1093/lifemedi/lnae031
Jiaojiao Chen, Maoxin Fang, Yuwei Li, Haodong Ding, Xinyu Zhang, Xiaoyi Jiang, Jinlan Zhang, Chengcheng Zhang, Zhigang Lu, Min Luo
{"title":"Cell surface protein-protein interaction profiling for biological network analysis and novel target discovery.","authors":"Jiaojiao Chen, Maoxin Fang, Yuwei Li, Haodong Ding, Xinyu Zhang, Xiaoyi Jiang, Jinlan Zhang, Chengcheng Zhang, Zhigang Lu, Min Luo","doi":"10.1093/lifemedi/lnae031","DOIUrl":"10.1093/lifemedi/lnae031","url":null,"abstract":"<p><p>The secretome is composed of cell surface membrane proteins and extracellular secreted proteins that are synthesized via secretory machinery, accounting for approximately one-third of human protein-encoding genes and playing central roles in cellular communication with the external environment. Secretome protein-protein interactions (SPPIs) mediate cell proliferation, apoptosis, and differentiation, as well as stimulus- or cell-specific responses that regulate a diverse range of biological processes. Aberrant SPPIs are associated with diseases including cancer, immune disorders, and illness caused by infectious pathogens. Identifying the receptor/ligand for a secretome protein or pathogen can be a challenging task, and many SPPIs remain obscure, with a large number of orphan receptors and ligands, as well as viruses with unknown host receptors, populating the SPPI network. In addition, proteins with known receptors/ligands may also interact with alternative uncharacterized partners and exert context-dependent effects. In the past few decades, multiple varied approaches have been developed to identify SPPIs, and these methods have broad applications in both basic and translational research. Here, we review and discuss the technologies for SPPI profiling and the application of these technologies in identifying novel targets for immunotherapy and anti-infectious agents.</p>","PeriodicalId":74073,"journal":{"name":"Life medicine","volume":"3 4","pages":"lnae031"},"PeriodicalIF":0.0,"publicationDate":"2024-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11749001/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143054626","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Life medicinePub Date : 2024-08-20eCollection Date: 2024-06-01DOI: 10.1093/lifemedi/lnae029
Si-Yi Su, Chuting He, Jie Ren, Moshi Song
{"title":"Global insights into aging: a multidisciplinary approach to understanding and addressing age-related challenges.","authors":"Si-Yi Su, Chuting He, Jie Ren, Moshi Song","doi":"10.1093/lifemedi/lnae029","DOIUrl":"10.1093/lifemedi/lnae029","url":null,"abstract":"<p><p>Aging has ascended to the forefront of scientific exploration, demanding a concerted global focus. The 2024 China Aging Science Conference and International Conference on Aging Biology hosted a panel discussion that brought international experts to delve into the complexities of aging research. The discussion underscores the imperative need for a multidisciplinary approach, integrating reductionist and holistic perspectives to unravel the molecular and epigenetic underpinnings of the aging process. Experts advocate for elucidating aging mechanisms and biomarkers, with a focus on translating scientific discoveries into tangible societal benefits. The discussion also emphasizes the importance of international and interdisciplinary collaborations, calling for more support to innovate for healthy aging and tackle age-related challenges.</p>","PeriodicalId":74073,"journal":{"name":"Life medicine","volume":"3 3","pages":"lnae029"},"PeriodicalIF":0.0,"publicationDate":"2024-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11749479/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143054537","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}