Frontiers in Cell and Developmental Biology最新文献

{"title":"Network analysis reveals potential mechanisms that determine the cellular identity of keratinocytes and corneal epithelial cells through the Hox/Gtl2-Dio3 miRNA axis.","authors":"Yanjie Guo, Weini Wu, Haoyu Chen, Xueqi Wang, Yi Zhang, Shuaipeng Li, Xueyi Yang","doi":"10.3389/fcell.2025.1475334","DOIUrl":"10.3389/fcell.2025.1475334","url":null,"abstract":"<p><p>During embryonic development, both corneal epithelial cells (CECs) and keratinocytes (KCs) originate from the surface ectoderm. As a result of this shared origin, corneal epithelial cells may exhibit the same characteristics as the skin epidermis in pathological situations, while keratinocytes are ideal seed cells for tissue-engineered corneas. However, how the identities of keratinocytes and corneal epithelial cells are determined is currently unclear. In this study, to investigate the molecular mechanisms determining the identity of keratinocytes and corneal epithelial cells, small RNA and mRNA sequencing analyses of these two cell types were performed. Analysis of the sequencing data revealed that almost all the miRNAs in the Gtl2-Dio3 imprinting region were highly expressed in keratinocytes and accounted for 30% of all differentially expressed miRNAs (DEMs). Since all the genes in the Gtl2-Dio3 imprinting region form a long polycistronic RNA under the control of the Gtl2 promoter, we next examined the expression of transcription factors and their binding near the Gtl2 locus. The findings indicated that the homeobox family dominated the differentially expressed transcription factors, and almost all <i>Hox</i> genes were silenced in corneal epithelial cells. Transcription binding site prediction and ChIP-seq revealed the binding of Hox proteins near the Gtl2 locus. Analysis of the Gtl-Dio3 miRNA target genes indicated that these miRNAs mainly regulate the Wnt signaling pathway and the PI3K-Akt signaling pathway. The crucial transcription factors in corneal epithelial cells, <i>Pax6</i>, <i>Otx2</i>, and <i>Foxc1</i>, are also targets of Gtl-Dio3 miRNAs. Our study revealed potential mechanisms that determine the cellular identity of keratinocytes and corneal epithelial cells through the Hox/Gtl2-Dio3 miRNA axis, which provides a new perspective for understanding the developmental regulation of corneal epithelial cells and the mechanisms of corneal opacity, as well as for establishing the groundwork for promoting the transdifferentiation of keratinocytes into corneal epithelial cells.</p>","PeriodicalId":12448,"journal":{"name":"Frontiers in Cell and Developmental Biology","volume":"13 ","pages":"1475334"},"PeriodicalIF":4.6,"publicationDate":"2025-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11782130/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143079207","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":"Volume-regulated anion channels conduct ATP in undifferentiated mammary cells and promote tumorigenesis in xenograft nude mouse.","authors":"Kishio Furuya, Hiroaki Hirata, Takeshi Kobayashi, Hiroshi Ishiguro, Masahiro Sokabe","doi":"10.3389/fcell.2024.1519642","DOIUrl":"https://doi.org/10.3389/fcell.2024.1519642","url":null,"abstract":"<p><p>The high interstitial ATP concentration in the cancer microenvironment is a major source of adenosine, which acts as a strong immune suppressor. However, the source of ATP release has not been elucidated. We measured ATP release during hypotonic stress using a real-time ATP luminescence imaging system in breast cell lines and in primary cultured mammary cells. In breast cell lines, ATP was released with a slowly rising diffuse pattern, whereas in primary cultured cells, ATP was intermittently released with transient-sharp peaks. The diffuse ATP release pattern changed to a transient-sharp pattern by cholera toxin treatment and the reverse change was induced by transforming growth factor (TGF) β treatment. DCPIB, an inhibitor of volume-regulated anion channels (VRACs), suppressed the diffuse pattern. The inflammatory mediator sphingosine-1-phosphate (S1P) induced a diffuse ATP release pattern isovolumetrically. Knockdown of the A isoform of leucine-rich repeat-containing protein 8 (LRRC8A), the essential molecular entity of VRACs, using shRNA suppressed the diffuse pattern. In the nude mouse xenograft model, LRRC8A knockdown suppressed the tumorigenesis of subcutaneously implanted breast cancer cells. These results suggest that abundantly expressed VRACs are a conduit of ATP release in undifferentiated cells, including cancer cells.</p>","PeriodicalId":12448,"journal":{"name":"Frontiers in Cell and Developmental Biology","volume":"12 ","pages":"1519642"},"PeriodicalIF":4.6,"publicationDate":"2025-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11774906/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143064674","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":"MicroRNAs in pancreatic cancer drug resistance: mechanisms and therapeutic potential.","authors":"Fangying Dong, Jing Zhou, Yijie Wu, Zhaofeng Gao, Weiwei Li, Zhengwei Song","doi":"10.3389/fcell.2024.1499111","DOIUrl":"https://doi.org/10.3389/fcell.2024.1499111","url":null,"abstract":"<p><p>Pancreatic cancer (PC) remains one of the most lethal malignancies, primarily due to its intrinsic resistance to conventional therapies. MicroRNAs (miRNAs), key regulators of gene expression, have been identified as crucial modulators of drug resistance mechanisms in this cancer type. This review synthesizes recent advancements in our understanding of how miRNAs influence treatment efficacy in PC. We have thoroughly summarized and discussed the complex role of miRNA in mediating drug resistance in PC treatment. By highlighting specific miRNAs that are implicated in drug resistance pathways, we provide insights into their functional mechanisms and interactions with key molecular targets. We also explore the potential of miRNA-based strategies as novel therapeutic approaches and diagnostic tools to overcome resistance and improve patient outcomes. Despite promising developments, challenges such as specificity, stability, and effective delivery of miRNA-based therapeutics remain. This review aims to offer a critical perspective on current research and propose future directions for leveraging miRNA-based interventions in the fight against PC.</p>","PeriodicalId":12448,"journal":{"name":"Frontiers in Cell and Developmental Biology","volume":"12 ","pages":"1499111"},"PeriodicalIF":4.6,"publicationDate":"2025-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11774998/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143064596","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":"Achieving myoblast engraftment into intact skeletal muscle via extracellular matrix.","authors":"Kitora Dohi, Yasuko Manabe, Nobuharu L Fujii, Yasuro Furuichi","doi":"10.3389/fcell.2024.1502332","DOIUrl":"10.3389/fcell.2024.1502332","url":null,"abstract":"<p><p>Cell therapy of skeletal muscles is a promising approach for the prevention of muscular diseases and age-related muscle atrophy. However, cell transplantation to treat muscle atrophy that does not involve disease, such as sarcopenia, is considered impossible because externally injected cells rarely engraft into non-injured muscle tissue. Additionally, skeletal muscle-specific somatic stem cells, called satellite cells, lose their ability to adhere to tissue after being cultured <i>in vitro</i> and transforming into myoblasts. To overcome these hurdles, we explored using extracellular matrix (ECM) components to create a niche environment conducive for myoblasts during transplantation. We demonstrated that myoblasts mixed with ECM components can be engrafted into intact skeletal muscle and significantly increase muscle mass in a mouse model. These findings implicate cell transplantation therapy as a viable option for the treatment of sarcopenia. The findings will inform advancements in regenerative medicine for skeletal muscles.</p>","PeriodicalId":12448,"journal":{"name":"Frontiers in Cell and Developmental Biology","volume":"12 ","pages":"1502332"},"PeriodicalIF":4.6,"publicationDate":"2025-01-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11772487/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143058556","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":"Ferroptosis and its relationship with cancer.","authors":"Chuanchao Su, Yiwen Xue, Siyu Fan, Xin Sun, Qian Si, Zhen Gu, Jingfei Wang, Runzhi Deng","doi":"10.3389/fcell.2024.1423869","DOIUrl":"10.3389/fcell.2024.1423869","url":null,"abstract":"<p><p>Marked by iron buildup and lipid peroxidation, ferroptosis is a relatively new regulatory cell death (RCD) pathway. Many diseases like cancer, myocardial ischemia-reperfusion injury (MIRI), neurological disorders and acute renal failure (AKI) are corelated with ferroptosis. The main molecular processes of ferroptosis discovered yet will be presented here, along with the approaches in which it interacts with tumour-associated signaling pathways and its uses in systemic therapy, radiation therapy, and immunotherapy managing tumors.</p>","PeriodicalId":12448,"journal":{"name":"Frontiers in Cell and Developmental Biology","volume":"12 ","pages":"1423869"},"PeriodicalIF":4.6,"publicationDate":"2025-01-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11772186/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143058570","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":"Stem cell status and prognostic applications of cuproptosis-associated lncRNAs in acute myeloid leukemia.","authors":"Zhuodong Chai, Zhongyue Yuan, Yifei Chen","doi":"10.3389/fcell.2024.1549294","DOIUrl":"10.3389/fcell.2024.1549294","url":null,"abstract":"<p><strong>Introduction: </strong>Acute myeloid leukemia (AML), a highly heterogeneous hematological malignancy, remains a major challenge in adult oncology. Stem cell research has highlighted the crucial role of long noncoding RNA (lncRNA) in regulating cellular differentiation and self-renewal processes, which are pivotal in AML pathogenesis and therapy resistance.</p><p><strong>Methods: </strong>This study explores the relationship between cuproptosis-related lncRNAs and AML prognosis, providing novel insights into their impact on hematopoietic stem and progenitor cells.</p><p><strong>Results: </strong>We collected clinical information from 214 AML patients in our center and analyzed the association between granulocyte recovery after chemotherapy, cuproptosis, and prognosis. Additionally, we developed a prognostic model-the cuproptosis-associated long noncoding RNA prognostic model (CRLPM)-y analyzing data from The Cancer Genome Atlas (TCGA). Patients were stratified into high- and low-risk groups based on CRLPM, revealing significant survival differences. High-risk patients demonstrated lower sensitivity to chemotherapeutic agents such as Axitinib, GSK429286A, Navitoclax, and ZM-447439, underscoring the need for alternative therapeutic strategies.</p><p><strong>Discussion: </strong>CRLPM offers a promising framework for integrating stem cell-focused approaches into personalized treatment regimens, paving the way for precision medicine in AML management.</p>","PeriodicalId":12448,"journal":{"name":"Frontiers in Cell and Developmental Biology","volume":"12 ","pages":"1549294"},"PeriodicalIF":4.6,"publicationDate":"2025-01-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11772438/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143058576","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 stumbling block in pancreatic cancer treatment: drug resistance signaling networks.","authors":"Jinming Liu, Biao Zhang, Bingqian Huang, Kexin Zhang, Fujia Guo, Zhizhou Wang, Dong Shang","doi":"10.3389/fcell.2024.1462808","DOIUrl":"10.3389/fcell.2024.1462808","url":null,"abstract":"<p><p>The primary node molecules in the cell signaling network in cancer tissues are maladjusted and mutated in comparison to normal tissues, which promotes the occurrence and progression of cancer. Pancreatic cancer (PC) is a highly fatal cancer with increasing incidence and low five-year survival rates. Currently, there are several therapies that target cell signaling networks in PC. However, PC is a \"cold tumor\" with a unique immunosuppressive tumor microenvironment (poor effector T cell infiltration, low antigen specificity), and targeting a single gene or pathway is basically ineffective in clinical practice. Targeted matrix therapy, targeted metabolic therapy, targeted mutant gene therapy, immunosuppressive therapy, cancer vaccines, and other emerging therapies have shown great therapeutic potential, but results have been disappointing. Therefore, we summarize the identified and potential drug-resistant cell signaling networks aimed at overcoming barriers to existing PC therapies.</p>","PeriodicalId":12448,"journal":{"name":"Frontiers in Cell and Developmental Biology","volume":"12 ","pages":"1462808"},"PeriodicalIF":4.6,"publicationDate":"2025-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11770040/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143052143","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":"Oral microbiota: the overlooked catalyst in cancer initiation and progression.","authors":"Xinlin Wang, Xin He, Bin Zhong","doi":"10.3389/fcell.2024.1479720","DOIUrl":"10.3389/fcell.2024.1479720","url":null,"abstract":"<p><p>The advancement of high-throughput sequencing technology in recent decades has led to a greater understanding of the components of the oral microbiota, providing a solid foundation for extensive research in this field. The oral microbiota plays an important role in an individual's overall health. It has been shown to be significantly correlated with chronic human diseases, including diabetes, rheumatoid arthritis, cardiovascular disease, periodontal disease, and Alzheimer's disease. Furthermore, tumor occurrence and development are closely related to the oral microbiome. Specific bacteria, such as <i>Fusobacterium nucleatum</i> (<i>F. nucleatum</i>), <i>Porphyromonas gingivalis</i> (<i>P. gingivalis</i>), <i>Streptococcus</i>, <i>Streptomyces</i>, <i>Prevotella</i>, and <i>Fibrophagy</i> gingivalis, play critical roles in cancer development. The oral microbiota has various oncogenic mechanisms, including bacterial inflammation, immunological suppression, tumor growth mediated by bacterial toxins, antiapoptotic activity, and carcinogenic effects. This paper reviews the role of the oral microbiota in the occurrence and progression of cancer and systematically elucidates the molecular mechanisms by which dysbiosis influences tumorigenesis and tumor progression. This information can provide a theoretical basis for exploring cancer treatment strategies and offer new insights for cancer prevention.</p>","PeriodicalId":12448,"journal":{"name":"Frontiers in Cell and Developmental Biology","volume":"12 ","pages":"1479720"},"PeriodicalIF":4.6,"publicationDate":"2025-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11769975/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143052181","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":"CD73/adenosine dynamics in treatment-induced pneumonitis: balancing efficacy with risks of adverse events in combined radio-immunotherapies.","authors":"Lena Gockeln, Florian Wirsdörfer, Verena Jendrossek","doi":"10.3389/fcell.2024.1471072","DOIUrl":"10.3389/fcell.2024.1471072","url":null,"abstract":"<p><p>Consolidation with PD-1/PD-L1-based immune checkpoint blockade after concurrent platinum-based chemo-radiotherapy has become the new standard of care for advanced stage III unresectable non-small cell lung cancer (NSCLC) patients. In order to further improve therapy outcomes, innovative combinatorial treatment strategies aim to target additional immunosuppressive barriers in the tumor microenvironment such as the CD73/adenosine pathway. CD73 and adenosine are known as crucial endogenous regulators of lung homeostasis and inflammation, but also contribute to an immunosuppressive tumor microenvironment. Furthermore, the CD73/adenosine pathway can also limit the immune-activating effects of cytotoxic therapies by degrading the pro-inflammatory danger molecule ATP, which is released into the tumor microenvironment and normal lung tissue upon therapy-induced cell damage. Thus, while targeting CD73 may enhance the efficacy of radio-immunotherapies in cancer treatment by mitigating tumor immune escape and improving immune-mediated tumor killing, it also raises concerns about increased immune-related adverse events (irAEs) in the normal tissue. In fact, combined radio-immunotherapies bear an increased risk of irAEs in the lungs, and additional pharmacologic inhibition of CD73 may further enhance the risk of overwhelming or overlapping pulmonary toxicity and thereby limit therapy outcome. This review explores how therapeutic interventions targeting CD73/adenosine dynamics could enhance radiation-induced immune activation in combined radio-immunotherapies, whilst potentially driving irAEs in the lung. We specifically investigate the interactions between radiotherapy and the CD73/adenosine pathway in radiation pneumonitis. Additionally, we compare the incidence of (radiation) pneumonitis reported in relevant trials to determine if there is an increased risk of irAEs in the clinical setting. By understanding these dynamics, we aim to inform future strategies for optimizing radio-immunotherapy regimens, ensuring effective cancer control while preserving pulmonary integrity and patient quality of life.</p>","PeriodicalId":12448,"journal":{"name":"Frontiers in Cell and Developmental Biology","volume":"12 ","pages":"1471072"},"PeriodicalIF":4.6,"publicationDate":"2025-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11769960/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143052175","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":"Telocytes in inflammatory bowel diseases: contributions to pathology and therapeutic potentials.","authors":"Ronaldo Paolo Panganiban, Christina McAninch, Marina Chulkina, Irina V Pinchuk","doi":"10.3389/fcell.2024.1452258","DOIUrl":"10.3389/fcell.2024.1452258","url":null,"abstract":"<p><p>Telocytes, a novel mesenchymal cell population, are characterized by their distinctive long and slender projections known as telopodes and have garnered significant interest since their formal introduction to the literature in 2010. These cells have been identified in various tissues, including the gastrointestinal (GI) tract, where they are suggested to play important roles in maintaining structural integrity, immune modulation, and barrier function. Inflammatory bowel diseases (IBD), which include Crohn's disease (CD) and ulcerative colitis (UC), are characterized by chronic inflammation and fibrosis. While limited information is available on the fate of telocytes in this group of diseases, it has been suggested that loss/plasticity of telocytes can be among the key factors contributing to their pathogenesis. This review focuses on the current understanding of telocytes, their structural features, and their distribution within the GI tract under gut homeostasis and IBD. We also discuss the roles of these cells in immune regulation and intestinal repair. We highlight evidence implicating telocytes in the pathogenesis of IBD and other chronic inflammatory diseases that share similar pathophysiological processes with IBD. Lastly, we discuss the current challenges in gut telocyte biology and the potential therapeutic implications of telocytes in IBD.</p>","PeriodicalId":12448,"journal":{"name":"Frontiers in Cell and Developmental Biology","volume":"12 ","pages":"1452258"},"PeriodicalIF":4.6,"publicationDate":"2025-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11770051/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143052185","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}