Cells最新文献

{"title":"The CD39/CD73/Adenosine and NAD/CD38/CD203a/CD73 Axis in Cutaneous T-Cell Lymphomas.","authors":"Liyun Lin, Gabriele Roccuzzo, Yuliya Yakymiv, Sara Marchisio, Erika Ortolan, Ada Funaro, Rebecca Senetta, Valentina Pala, Martine Bagot, Adèle de Masson, Maxime Battistella, Emmanuella Guenova, Simone Ribero, Pietro Quaglino","doi":"10.3390/cells14040309","DOIUrl":"10.3390/cells14040309","url":null,"abstract":"<p><p>Cutaneous T-cell lymphoma (CTCL), characterized by malignant T-cell proliferation primarily in the skin, includes subtypes such as mycosis fungoides (MF) and Sézary syndrome (SS). The tumor microenvironment (TME) is central to their pathogenesis, with flow cytometry and histology being the gold standards for detecting malignant T cells within the TME. Alongside emerging molecular markers, particularly clonality analysis, these tools are indispensable for accurate diagnosis and treatment planning. Of note, adenosine signaling within the TME has been shown to suppress immune responses, affecting various cell types. The expression of CD39, CD73, and CD38, enzymes involved in adenosine production, can be elevated in MF and SS, contributing to immune suppression. Conversely, the expression of CD26, part of the adenosine deaminase/CD26 complex, that degrades adenosine, is often lost by circulating tumoral cells. Flow cytometry has demonstrated increased levels of CD39 and CD73 on Sézary cells, correlating with disease progression and prognosis, while CD38 shows a variable expression, with its prognostic significance remaining under investigation. Understanding these markers' roles in the complexity of TME-mediated immune evasion mechanisms might enhance diagnostic precision and offer new therapeutic targets in CTCL.</p>","PeriodicalId":9743,"journal":{"name":"Cells","volume":"14 4","pages":""},"PeriodicalIF":5.1,"publicationDate":"2025-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11854806/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143490948","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":"Role of Hemocytes in the Aging of Drosophila Male Germline.","authors":"Virginia Varga, Janka Szinyákovics, Anikó Bebes, Fanni Szikszai, Tibor Kovács","doi":"10.3390/cells14040315","DOIUrl":"10.3390/cells14040315","url":null,"abstract":"<p><p>Stem cells are essential for the proper functioning of tissues, replacing damaged, senescent cells to ensure tissue regeneration. However, as age advances, the number of these stem cells can change, and their self-renewal abilities can become impaired, leading to disruption of homeostasis, loss of regenerative capacity, and, ultimately, deterioration of tissue function. In <i>Drosophila</i> testis, in addition to the germline and somatic cells involved in spermatogenesis, there are immune cells (hemocytes) with macrophage function. In our study, we aimed to investigate the role of hemocytes in maintaining germline stem cells throughout their lifespan. Our results show that in the absence of plasmatocytes and crystal immune cells, the number of germline stem cells (GSCs) and apoptotic germline cells also increases significantly during senescence, which may have detrimental effects on the differentiation processes of germline cells. The size of the hub increases in aged male testes. It is therefore conceivable that changes in the hub may induce dysfunction of differentiation processes. The fertility of aged immunodeficient animals is decreased. Furthermore, we show that the expression of the JAK/STAT signaling pathway, which is essential for the maintenance of the stem cell <i>niche</i>, is impaired in the lack of hemocytes. We found an increased expression of Socs36e, an inhibitor of JAK-STAT, which correlates with decreased JAK-STAT activity. Overexpression of Socs36e in the apical part of the germline led to a phenotype similar to the immunodeficient aged germline, where an increased GSC number and hub size were also observed. However, spermatogenesis was also disturbed in this case. Our study shows that hemocytes are required to regulate the number of GSCs. This regulation could be mediated through the JAK-STAT signaling pathway. These results may help to provide a more complex insight into the relationships between immune cells and stem cells.</p>","PeriodicalId":9743,"journal":{"name":"Cells","volume":"14 4","pages":""},"PeriodicalIF":5.1,"publicationDate":"2025-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11854897/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143490868","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":"Therapeutic Targeting of the Galectin-1/miR-22-3p Axis Regulates Cell Cycle and EMT Depending on the Molecular Subtype of Breast Cancer.","authors":"Ju Yeon Kim, Jun Ho Lee, Eun Jung Jung, Young Sim Son, Hee Jin Park, Jae Myung Kim, Taejin Park, Sang-Ho Jeong, Jinkwon Lee, Tae Han Kim, Seon Min Lee, Jeong Doo Heo","doi":"10.3390/cells14040310","DOIUrl":"10.3390/cells14040310","url":null,"abstract":"<p><p>Breast cancer is a highly heterogeneous disease; hence, it is crucial to understand its biology and identify new targets for the development of effective treatments. Galectin-1 is known to play an oncogenic role in breast cancer progression. It is known that oncogenic factors can influence cancer progression through interactions with miRNAs. The purpose of this study is to identify the clinical significance and biological role of galectin-1 and miR-22-3p in cancer progression according to the molecular subtype of breast cancer. We analyzed the expression of galectin-1 and miR-22-3p using cancer tissues and the correlation with clinical pathological characteristics. In addition, we investigated the regulation of the cell cycle and EMT processes of cancer progression through the galectin-1/miR-22-3p axis using cell lines of different breast cancer subtypes. miR-22-3p negatively regulates galectin-1 expression and the two molecules have opposite patterns of oncogenic and tumor-suppressive functions, respectively; furthermore, these two molecules are associated with metastasis-free survival. Cell experiments showed that miR-22-3p overexpression and galectin-1 knockdown inhibited the proliferation and invasion of breast cancer cells. Galectin-1 regulates different cancer progression pathways depending on the molecular subtype. In hormone receptor-positive breast cancer cells, galectin-1 knockdown mainly inhibited cell cycle-related substances and induced G0/G1 arrest, whereas in triple-negative breast cancer cells, it suppressed molecules related to the epithelial-mesenchymal transition pathway. In conclusion, the miR-22-3p/galectin-1 axis regulates different cancer metastasis mechanisms depending on the specific molecular subtype of breast cancer, and miR-22-3p/galectin-1 axis modulation may be a novel target for molecular subtype-specific personalized treatment.</p>","PeriodicalId":9743,"journal":{"name":"Cells","volume":"14 4","pages":""},"PeriodicalIF":5.1,"publicationDate":"2025-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11854374/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143490958","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":"Establishing Minimum Criteria for Stem Cells from Human Exfoliated Deciduous Teeth (SHEDs) Cultured in Human Platelet Lysate (hPL)-Contained Media as Cell Therapy Candidates: Characterization and Predictive Analysis of Secretome Effects.","authors":"Ji-Young Yoon, Bình Do Quang, Ji-Sun Shin, Jong-Bin Kim, Jun Hee Lee, Hae-Won Kim, Jung-Hwan Lee","doi":"10.3390/cells14040316","DOIUrl":"10.3390/cells14040316","url":null,"abstract":"<p><p>SHEDs have demonstrated significant potential in cell therapy due to their superior proliferation rate, self-renewal and differentiation capacity (particularly neurogenesis attributed to their neural crest origin), and the less invasive procedure required for tissue collection compared to other stem cells. However, there is no established criterion to verify the minimum qualification to select one from numerous candidates, especially for SHEDs' cultured FBS-free medium for clinic application. For that, we performed a characteristic analysis containing the growth rate, colony-forming unit (CFU) number, average colony size, and migration capacity with hPL-cultured SHEDs from 21 different donors, and we suggest the result as a minimum standard to filter out unqualified candidates. In addition, in the secretome analysis to predict the paracrine effect, it was found that upregulated proteins compared to the control were related to angiogenesis, immune response, and BMP signaling, and this was found to have a strong correlation only with protein concentration. This study presents a minimum standard for selecting cell therapy candidates and suggests the protein concentration of a conditioned medium as a cost-effective tool to expect the paracrine effect of SHEDs.</p>","PeriodicalId":9743,"journal":{"name":"Cells","volume":"14 4","pages":""},"PeriodicalIF":5.1,"publicationDate":"2025-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11854447/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143490921","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":"Comparison Between Signal Transduction Pathway Activity in Blood Cells of Sepsis Patients and Laboratory Models.","authors":"Wilbert Bouwman, Reinier Raymakers, Tom van der Poll, Anja van de Stolpe","doi":"10.3390/cells14040311","DOIUrl":"10.3390/cells14040311","url":null,"abstract":"<p><p>Sepsis represents a serious disease burden that lacks effective treatment. Drug development for sepsis requires laboratory models that adequately represent sepsis patients. Simultaneous Transcriptome-based Activity Profiling of Signal Transduction Pathway (STAP-STP) technology quantitatively infers STP activity from mRNA levels of target genes of the STP-associated transcription factor. Here, we used STAP-STP technology to compare STP activities between sepsis patients and lipopolysaccharide (LPS)-based models. Activity scores of Androgen Receptor (AR), TGFβ, NFκB, JAK-STAT1/2, and JAK-STAT3 STPs were calculated based on publicly available transcriptome data. Peripheral blood mononuclear cells (PBMCs) from patients with Gram-negative sepsis, nor PBMCs stimulated with LPS in vitro, showed altered STP activity. Increased NFκB, JAK-STAT1/2, and JAK-STAT3 STP activity was found in whole blood stimulated with LPS in vitro, and in whole blood obtained after intravenous injection of LPS in humans in vivo; AR and TGFβ STP activity only increased in the in vivo LPS model. These results resembled previously reported STP activity in whole blood of sepsis patients. We provide the first comparison of STP activity between patients with sepsis and laboratory model systems. Results are of use for the refinement of sepsis model systems for rational drug development.</p>","PeriodicalId":9743,"journal":{"name":"Cells","volume":"14 4","pages":""},"PeriodicalIF":5.1,"publicationDate":"2025-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11854017/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143490879","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 Critical Role of Intracellular PD-L1 in Promoting Ovarian Cancer Progression.","authors":"Rui Huang, Brad Nakamura, Rosemary Senguttuvan, Yi-Jia Li, Antons Martincuks, Rania Bakkar, Mihae Song, David K Ann, Lorna Rodriguez-Rodriguez, Hua Yu","doi":"10.3390/cells14040314","DOIUrl":"10.3390/cells14040314","url":null,"abstract":"<p><p>Disrupting the interaction between tumor-cell surface PD-L1 and T cell membrane PD-1 can elicit durable clinical responses. However, only about 10% of ovarian cancer patients respond to PD-1/PD-L1 blockade. Here, we show that PD-L1 expression in ovarian cancer-patient tumors is predominantly intracellular. Notably, PARP inhibitor treatment highly increased intracellular PD-L1 accumulation in both ovarian cancer-patient tumor samples and cell lines. We investigated whether intracellular PD-L1 might play a critical role in ovarian cancer progression. Mutating the PD-L1 acetylation site in PEO1 and ID8<i>^Brca1-/-</i> ovarian cancer cells significantly decreased PD-L1 levels and impaired colony formation, which was accompanied by cell cycle G2/M arrest and apoptosis induction. PEO1 and ID8<i>^Brca1-/-</i> tumors with PD-L1 acetylation site mutation also exhibited significantly reduced growth in mice. Furthermore, targeting intracellular PD-L1 with a cell-penetrating antibody effectively decreased ovarian tumor-cell intracellular PD-L1 level and induced tumor-cell growth arrest and apoptosis, as well as enhanced DNA damage and STING activation, both in vitro and in vivo. In conclusion, we have shown the critical role of intracellular PD-L1 in ovarian cancer progression.</p>","PeriodicalId":9743,"journal":{"name":"Cells","volume":"14 4","pages":""},"PeriodicalIF":5.1,"publicationDate":"2025-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11853747/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143490913","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":"Rotavirus Spreads in a Spatially Controlled Manner.","authors":"Gianna V Passarelli, Patricio Doldan, Camila Metz-Zumaran, Yagmur Keser, Steeve Boulant, Megan L Stanifer","doi":"10.3390/cells14040313","DOIUrl":"10.3390/cells14040313","url":null,"abstract":"<p><p>Rotavirus is an enteric virus that leads to 200,000 deaths worldwide every year. The live-cell imaging evaluating rotavirus infection of MA104 cells revealed that rotavirus replication and spread occurs in a spatially controlled manner. Specifically, following initial rotavirus infection, the infected cells die, and the second round of infection occurs in the restricted area surrounding the initially infected cell. Interestingly, we found that the time required to establish the secondary infection is shorter compared to the time required for the initial infection. To determine if this increase in the kinetic of secondary infection was due to the early release of viruses or priming of the cells that are infected during the secondary infection, we used a combination of live-cell microscopy, trypsin neutralization assays, and the pharmacological inhibition of calcium signaling. Together, our results show that the second round of infection required rotavirus to be released and accessible to extracellular proteases. In addition, we found that the calcium wave induced upon rotavirus infection was critical for initial infection but did not play a role in the establishment of a secondary infection. Finally, we uncovered that high viral titers released from the initial infection were sufficient to accelerate the rate of the secondary infection.</p>","PeriodicalId":9743,"journal":{"name":"Cells","volume":"14 4","pages":""},"PeriodicalIF":5.1,"publicationDate":"2025-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11854656/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143490870","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":"Exploratory Review and In Silico Insights into circRNA and RNA-Binding Protein Roles in γ-Globin to β-Globin Switching.","authors":"Alawi Habara","doi":"10.3390/cells14040312","DOIUrl":"10.3390/cells14040312","url":null,"abstract":"<p><p>β-globin gene cluster regulation involves complex mechanisms to ensure proper expression and function in RBCs. During development, switching occurs as γ-globin is replaced by β-globin. Key regulators, like BCL11A and ZBTB7A, repress γ-globin expression to facilitate this transition with other factors, like KLF1, LSD1, and PGC-1α; these regulators ensure an orchestrated transition from γ- to β-globin during development. While these mechanisms have been extensively studied, circRNAs have recently emerged as key contributors to gene regulation, but their role in β-globin gene cluster regulation remains largely unexplored. Although discovered in the 1970s, circRNAs have only recently been recognized for their functional roles, particularly in interactions with RNA-binding proteins. Understanding how circRNAs contribute to switching from γ- to β-globin could lead to new therapeutic strategies for hemoglobinopathies, such as sickle cell disease and β-thalassemia. This review uses the circAtlas 3.0 database to explore circRNA expressions in genes related to switching from γ- to β-globin expression, focusing on blood, bone marrow, liver, and spleen. It emphasizes the exploration of the potential interactions between circRNAs and RNA-binding proteins involved in β-globin gene cluster regulatory mechanisms, further enhancing our understanding of β-globin gene cluster expression.</p>","PeriodicalId":9743,"journal":{"name":"Cells","volume":"14 4","pages":""},"PeriodicalIF":5.1,"publicationDate":"2025-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11854342/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143490923","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":"The Emerging Role of the Histone H2AK13/15 Ubiquitination: Mechanisms of Writing, Reading, and Erasing in DNA Damage Repair and Disease.","authors":"Qi Shu, Yun Liu, Huasong Ai","doi":"10.3390/cells14040307","DOIUrl":"10.3390/cells14040307","url":null,"abstract":"<p><p>Histone modifications serve as molecular switches controlling critical cellular processes. The ubiquitination of histone H2A at lysines 13 and 15 (H2AK13/15ub) is a crucial epigenetic modification that coordinates DNA repair and genome stability during the DNA damage response (DDR). This epigenetic mark is dynamically regulated by three functional protein groups: \"writer\" enzymes (e.g., E3 ubiquitin ligase RNF168 that catalyzes H2AK13/15ub formation), \"reader\" proteins (including 53BP1 and BRCA1-BARD1 that recognize the mark to guide DNA repair), and \"eraser\" deubiquitinases (such as USP3 and USP16 that remove the modification). Dysregulation of the precisely coordinated network of H2AK13/15ub is strongly associated with various diseases, including RIDDLE syndrome, neurodegenerative disorders, immune deficiencies, and breast cancer. This review systematically analyzes the dynamic regulation of H2AK13/15ub in DDR and explores its therapeutic potential for disease intervention.</p>","PeriodicalId":9743,"journal":{"name":"Cells","volume":"14 4","pages":""},"PeriodicalIF":5.1,"publicationDate":"2025-02-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11854596/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143490951","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":"Prenatal Exposure to Metals Is Associated with Placental Decelerated Epigenetic Gestational Age in a Sex-Dependent Manner in Infants Born Extremely Preterm.","authors":"Katelyn K Huff, Kyle R Roell, Lauren A Eaves, Thomas Michael O'Shea, Rebecca C Fry","doi":"10.3390/cells14040306","DOIUrl":"10.3390/cells14040306","url":null,"abstract":"<p><p>Prenatal exposure to metals can influence fetal programming via DNA methylation and has been linked to adverse birth outcomes and long-term consequences. Epigenetic clocks estimate the biological age of a given tissue based on DNA methylation and are potential health biomarkers. This study leveraged the Extremely Low Gestational Age Newborn (ELGAN) study (<i>n</i> = 265) to evaluate associations between umbilical cord tissue concentrations of 11 metals as single exposures as well as mixtures in relation to (1) placental epigenetic gestational age acceleration (eGAA) and the (2) methylation status of the Robust Placental Clock (RPC) CpGs. Linear mixed effect regression models were stratified by infant sex. Both copper (Cu) and manganese (Mn) were significantly associated with a decelerated placental eGA of -0.98 (95% confidence interval (CI): -1.89, -0.07) and -0.90 weeks (95% CI: -1.78, -0.01), respectively, in male infants. Cu and Mn levels were also associated with methylation at RPC CpGs within genes related to processes including energy homeostasis and inflammatory response in placenta. Overall, these findings suggest that prenatal exposures to Cu and Mn impact placental eGAA in a sex-dependent manner in ELGANs, and future work could examine eGAA as a potential mechanism mediating in utero metal exposures and later life consequences.</p>","PeriodicalId":9743,"journal":{"name":"Cells","volume":"14 4","pages":""},"PeriodicalIF":5.1,"publicationDate":"2025-02-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11854159/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143490986","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}