Frontiers in Cell and Developmental Biology最新文献

{"title":"PFKP in malignant tumors: bridging metabolic reprogramming, post-translational modifications, and the immunosuppressive microenvironment.","authors":"Jing-Jing Zhao, Gangyuan Ma, Rui Zong, Jinlan Zhong, Yicheng Zhao, Liang Liu, Runze Li","doi":"10.3389/fcell.2026.1944968","DOIUrl":"https://doi.org/10.3389/fcell.2026.1944968","url":null,"abstract":"<p><p>Metabolic reprogramming is a hallmark of malignant tumors. Platelet-type phosphofructokinase (PFKP), a rate-limiting enzyme in glycolysis, is aberrantly overexpressed across diverse cancers and promotes tumor proliferation, invasion, and metastasis through both metabolic and non-metabolic pathways. The enzymatic activity, stability, and subcellular localization of PFKP are dynamically regulated by post-translational modifications-including phosphorylation, ubiquitination, acetylation, and lactylation-as well as by protein-protein interaction networks. Upon nuclear translocation, PFKP dissociates from glycolytic flux and engages in oncogenic transcriptional regulation. Moreover, PFKP upregulates PD-L1 expression, alters chemokine profiles, disrupts immune cell infiltration, and fosters an immunosuppressive microenvironment that facilitates immune evasion. Emerging evidence suggests PFKP holds diagnostic and prognostic potential, yet direct targeting evidence remains lacking, and most inhibitor studies are confined to preclinical models. This review synthesizes recent advances in PFKP research, focusing on its regulatory networks in tumor metabolism, post-translational modifications, protein interactions, and immune remodeling. We critically evaluate current controversies, unresolved questions, and translational barriers, and propose future directions-including epigenetic regulation, functional characterization of interacting partners, and combination strategies with immunotherapy-to inform precision oncology and targeted therapeutic development.</p>","PeriodicalId":12448,"journal":{"name":"Frontiers in Cell and Developmental Biology","volume":"14 ","pages":"1944968"},"PeriodicalIF":5.3,"publicationDate":"2026-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13631397/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149106752","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":"Single-cell transcriptomic characterization of a human MDS hematopoietic dataset and in vitro validation of apoptosis-related venetoclax resistance in human MDS-L cells.","authors":"Tianjiao Huang, Shiyu Li, Hong Zhou, Heng Guo, Suliang Wang","doi":"10.3389/fcell.2026.1947721","DOIUrl":"https://doi.org/10.3389/fcell.2026.1947721","url":null,"abstract":"<p><strong>Background: </strong>Myelodysplastic syndromes (MDS) are heterogeneous clonal hematopoietic disorders in which dysregulated apoptosis, oxidative stress, and adaptive survival signaling contribute to disease persistence and therapeutic resistance. Venetoclax (VEN) targets BCL-2-dependent survival, but resistance is frequently accompanied by compensatory survival programs. Whether ferroptosis-associated transcriptional states are dynamically remodeled during VEN treatment and participate in this adaptive phenotype remains incompletely understood.</p><p><strong>Methods: </strong>We analyzed two independent human MDS single-cell RNA-sequencing cohorts together with an <i>in vitro</i> VEN-resistant MDS-L model. GSE241417 was used to characterize longitudinal and cell-state-specific ferroptosis-associated transcriptional patterns, whereas GSE180298 provided independent single-cell validation. Longitudinal module scores were summarized across major hematopoietic states and treatment stages. Apoptosis/proliferation- and ferroptosis-related genes were further examined by qRT-PCR in parental and VEN-resistant MDS-L cells.</p><p><strong>Results: </strong>Single-cell analysis revealed marked heterogeneity of ferroptosis-associated transcriptional programs across MDS hematopoietic populations. Longitudinal trajectories in GSE241417 demonstrated nonuniform, treatment-stage- and cell-state-dependent remodeling of ferroptosis balance, inflammatory context, and survival-associated programs. The independent GSE180298 cohort reproduced major disease-associated ferroptosis-related transcriptional differences. In VEN-resistant MDS-L cells, <i>MCL1</i>, <i>BCL2L1</i>, <i>MKI67</i>, <i>GPX4</i>, <i>SLC7A11</i>, and <i>NFE2L2</i> were increased, whereas <i>BCL2</i>, <i>DDIT3</i>, <i>ACSL4</i>, and <i>NCOA4</i> were decreased, indicating coordinated adaptation of apoptotic and ferroptosis-related pathways.</p><p><strong>Conclusion: </strong>This study reveals cell-state-dependent and temporally dynamic ferroptosis-associated remodeling in MDS and identifies a coordinated apoptosis-redox transcriptional program associated with VEN resistance. The integration of longitudinal single-cell analysis, independent single-cell validation, and targeted qRT-PCR supports ferroptosis-defense pathways as a biologically relevant component of VEN-resistant adaptation and provides a rationale for future combination strategies that address both apoptotic dependence and redox-state plasticity.</p>","PeriodicalId":12448,"journal":{"name":"Frontiers in Cell and Developmental Biology","volume":"14 ","pages":"1947721"},"PeriodicalIF":5.3,"publicationDate":"2026-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13630996/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149106861","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":"Diabetic cardiomyopathy as a disorder of proteostatic maladaptation: context-dependent ubiquitin-specific protease networks.","authors":"Xiangyun Meng, Shuming Guo, Hui Lin, Ruchao Li, Wei Peng, Lingang Sun, Xiaowei Shi, Lixia Yang","doi":"10.3389/fcell.2026.1910665","DOIUrl":"https://doi.org/10.3389/fcell.2026.1910665","url":null,"abstract":"<p><p>Diabetic cardiomyopathy (DCM) is a multidimensional myocardial remodeling disorder driven by interconnected metabolic, inflammatory, ferroptotic, autophagic and fibrotic programs, yet the post-translational mechanisms that convert diabetic stress into persistent injury remain incompletely integrated. Ubiquitin-specific proteases (USPs) regulate substrate stability, ubiquitin-chain architecture and signaling-complex dynamics and therefore represent an important proteostatic layer in DCM. Rather than assigning fixed protective or maladaptive identities to individual enzymes, this review organizes current evidence according to specific USP-substrate axes and their cellular and disease contexts. Predominantly protective axes include USP28-PPARα/Mfn2, USP8-Parkin, USP13-NLRP3, USP20-p62/STING, USP18-dependent stabilization of Notch1 or FOXC2, and the endothelial USP33-ATG7/FIS1 pathway. Predominantly injurious axes include USP38-ACAD11, USP14-VDAC1 and USP24-associated ferroptotic and autophagy-disruptive signaling. USP7 exemplifies substrate-dependent bidirectionality: USP7-PGC1β promotes metabolic dysfunction, whereas USP7-NRF2 supports GPX4-dependent ferroptosis resistance during empagliflozin treatment. By integrating these axes across pathological modules and cardiac cell types, this review reframes DCM as a disorder of context-dependent proteostatic maladaptation and highlights substrate-resolved USP regulation as a priority for future mechanistic and translational investigation.</p>","PeriodicalId":12448,"journal":{"name":"Frontiers in Cell and Developmental Biology","volume":"14 ","pages":"1910665"},"PeriodicalIF":5.3,"publicationDate":"2026-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13631399/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149106604","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":"Human stem cell-based embryo models: from self-organization to recapitulating development.","authors":"Dongsong Liu, Tianyao He","doi":"10.3389/fcell.2026.1857249","DOIUrl":"https://doi.org/10.3389/fcell.2026.1857249","url":null,"abstract":"<p><p>Human stem cell-based embryo models (hereafter referred to as embryo models) are a rapidly evolving field at the intersection of developmental biology and bioengineering. In this review, we examine design principles, material systems, and engineering approaches that enable the construction of models arising from pluripotent stem cells. We consider how three-dimensional environments, synthetic hydrogels, and spatiotemporal modulation of morphogenetic signals guide self-organization. Together, these factors enable the recapitulation of stages from blastocyst formation to early organogenesis. We then discuss opportunities of these engineered systems in disease modeling and developmental toxicity screening. We also address the scaling issues and biomanufacturing limitations that must be overcome to enable standardized, high-fidelity production.</p>","PeriodicalId":12448,"journal":{"name":"Frontiers in Cell and Developmental Biology","volume":"14 ","pages":"1857249"},"PeriodicalIF":5.3,"publicationDate":"2026-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13627765/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149106714","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":"Correction: Characterization of the roles of amphiregulin and transforming growth factor β1 in microvasculature-like formation in human granulosa-lutein cells.","authors":"Hui Li, Hsun-Ming Chang, Saijiao Li, Christian Klausen, Zhendan Shi, Peter C K Leung","doi":"10.3389/fcell.2026.1977869","DOIUrl":"https://doi.org/10.3389/fcell.2026.1977869","url":null,"abstract":"<p><p>[This corrects the article DOI: 10.3389/fcell.2022.968166.].</p>","PeriodicalId":12448,"journal":{"name":"Frontiers in Cell and Developmental Biology","volume":"14 ","pages":"1977869"},"PeriodicalIF":5.3,"publicationDate":"2026-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13628639/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149106600","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":"Correction: Unveiling the inflammatory link: integrated analysis identifies BMP7 and PPBP as key genes in obstructive sleep apnea-related atrial fibrillation.","authors":"Feng Li, Xing Xu, Yi-Qiu Hu, Cheng-Peng Zhang, Yi-Wei Shen, Chi Geng, Jia-Peng Chu, Hui-Yu Bai, Xiao-Song Gu, Hui Li","doi":"10.3389/fcell.2026.1988944","DOIUrl":"https://doi.org/10.3389/fcell.2026.1988944","url":null,"abstract":"<p><p>[This corrects the article DOI: 10.3389/fcell.2026.1914540.].</p>","PeriodicalId":12448,"journal":{"name":"Frontiers in Cell and Developmental Biology","volume":"14 ","pages":"1988944"},"PeriodicalIF":5.3,"publicationDate":"2026-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13627899/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149106574","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":"Reconstitution of genome remodeling using <i>Xenopus</i> egg extracts.","authors":"Katherine G Lenz, Coral Y Zhou","doi":"10.3389/fcell.2026.1932329","DOIUrl":"https://doi.org/10.3389/fcell.2026.1932329","url":null,"abstract":"<p><p>Changes in 3D genome organization drive critical cellular transitions including cell division and differentiation. Cytoplasmic extracts derived from eggs of the African clawed frog <i>Xenopus laevis</i> offer a powerful system for reconstituting genome remodeling events <i>in vitro</i> and dissecting the underlying biochemical mechanisms. Female <i>X. laevis</i> produce thousands of large eggs that can be readily lysed by centrifugation to yield egg cytoplasm-commonly referred to as egg extract. This extract contains the full complement of molecules required to support multiple rounds of chromatin assembly, nuclear formation, DNA replication and repair, and chromosome segregation. Addition of an exogenous DNA source triggers rapid, highly reproducible remodeling that can be monitored by fluorescence microscopy, gel electrophoresis, or genomics approaches. The biochemical tractability of this system has historically been instrumental in revealing fundamental mechanisms of chromatin assembly and remodeling. This review summarizes the major genome remodeling assays enabled by <i>Xenopus</i> egg extracts and highlights recent advances in the field. We also outline promising new directions for leveraging this system to unravel the molecular basis of speciation and polyploidy.</p>","PeriodicalId":12448,"journal":{"name":"Frontiers in Cell and Developmental Biology","volume":"14 ","pages":"1932329"},"PeriodicalIF":5.3,"publicationDate":"2026-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13627764/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149106771","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":"Glutamine metabolism and its roles in tumor radiotherapy by regulating DNA damage repair.","authors":"Yuwei Huang, Huanhuan Wang, Shuang Zhang, Zhenyang Jiang, Ruolin Shen, Weiqin Chang, Xin Jiang","doi":"10.3389/fcell.2026.1915673","DOIUrl":"https://doi.org/10.3389/fcell.2026.1915673","url":null,"abstract":"<p><strong>Background: </strong>As a conditionally essential amino acid that is required by tumor cells, glutamine serves as a key metabolic hub in tumor cells, functioning both as a carbon source for the tricarboxylic acid cycle and lipid synthesis and as a nitrogen source for amino acid and nucleotide biosynthesis. Cancer cells reprogram glutamine metabolism to enhance its uptake and utilization, thereby supporting anabolic demands, maintaining redox homeostasis, and ensuring genomic stability. The efficacy of radiotherapy against malignancies largely depends on tumor cell radiosensitivity, which is influenced by DNA damage repair capacity, microenvironmental hypoxia, and cancer stem cells. Growing evidence indicates that glutamine metabolism significantly modulates tumor radiosensitivity by regulating the supply of key substrates for DNA damage repair, affecting repair protein function through post-translational modifications, and altering chromatin architecture.</p><p><strong>Methods: </strong>We performed a comprehensive literature search across PubMed and Web of Science, focusing on studies investigating the interplay among glutamine metabolism, DNA damage response, and tumor radiosensitivity. Based on critical analysis and synthesis of the retrieved literature, we propose an integrated framework linking metabolic rewiring to DNA repair modulation in the context of radiotherapy.</p><p><strong>Results: </strong>This review identifies three principal mechanisms by which glutamine metabolism may regulate the DNA damage response in tumors: (1) supplying essential substrates for DNA repair, including purines and pyrimidines derived from glutamine-dependent biosynthesis; (2) modulating the activity and function of DNA repair proteins through O-GlcNAcylation and PARylation as critical post-translational modifications, as well as regulating chromatin accessibility via histone modifications; and (3) maintaining redox homeostasis and counteracting iron-dependent lipid peroxidation to modulate ferroptosis susceptibility following irradiation. Notably, targeted inhibition of glutamine metabolism significantly enhances tumor radiosensitivity and suppresses tumor growth, demonstrating the therapeutic potential of metabolic intervention.</p><p><strong>Conclusion: </strong>Glutamine metabolism plays a multifaceted role in regulating the DNA damage response and tumor radiosensitivity. Targeting glutamine metabolic pathways, particularly through substrate supply deprivation, post-translational modification interference, or chromatin remodeling modulation, may represent a rational strategy for radiosensitization. This review provides a theoretical basis for the development of novel combination regimens integrating glutamine metabolism inhibitors with radiotherapy.</p>","PeriodicalId":12448,"journal":{"name":"Frontiers in Cell and Developmental Biology","volume":"14 ","pages":"1915673"},"PeriodicalIF":5.3,"publicationDate":"2026-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13627316/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149106769","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":"TRPV1 mediates mitochondrial dysfunction in hyperthermia-induced ameloblast mineralization defects.","authors":"Jingyi Li, Jing Fu, Yiwen Pan, Huiwen Zheng, Xianghui Xing","doi":"10.3389/fcell.2026.1903038","DOIUrl":"https://doi.org/10.3389/fcell.2026.1903038","url":null,"abstract":"<p><strong>Background: </strong>Enamel hypomineralization is a prevalent developmental dental defect associated with several early-life risk factors, including hyperthermia. However, the cellular mechanisms linking hyperthermia to impaired enamel mineralization remain unclear. This study investigated the potential role of transient receptor potential vanilloid 1 (TRPV1) in hyperthermia-associated ameloblast dysfunction.</p><p><strong>Methods: </strong>Using a mouse ameloblast-lineage cell (ALC) model, we performed quantitative real-time PCR (qRT-PCR), alkaline phosphatase (ALP) staining, Alizarin Red S (ARS) staining, RNA sequencing, immunohistochemistry, Western blotting, molecular intervention experiments, intracellular and mitochondrial calcium imaging, reactive oxygen species measurements, and mitochondrial functional assays.</p><p><strong>Results: </strong>RNA sequencing and immunohistochemistry identified TRPV1 as a candidate heat-responsive channel expressed in ameloblasts. Hyperthermia was associated with reduced mineralization-related markers, increased intracellular and mitochondrial Ca²⁺ signals and reactive oxygen species levels, decreased mitochondrial membrane potential, and impaired ATP content and NAD⁺/NADH ratio. Pharmacological inhibition and genetic suppression of TRPV1 partially alleviated these hyperthermia-associated alterations.</p><p><strong>Conclusion: </strong>These findings support the involvement of TRPV1 in hyperthermia-associated calcium dysregulation, mitochondrial dysfunction, and impaired mineralization-related responses in cultured ALCs. The results provide a testable framework for further in vivo investigation.</p>","PeriodicalId":12448,"journal":{"name":"Frontiers in Cell and Developmental Biology","volume":"14 ","pages":"1903038"},"PeriodicalIF":5.3,"publicationDate":"2026-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13627420/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149105839","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":"Mechanoresponsive reprogramming of tumor-associated macrophages during cancer progression.","authors":"Dayeon Kim, Yeonjae Kim, Jihye Lee, Saumendra Kumar Bajpai, Dong-Hwee Kim","doi":"10.3389/fcell.2026.1915582","DOIUrl":"https://doi.org/10.3389/fcell.2026.1915582","url":null,"abstract":"<p><p>Tumor-associated macrophages (TAMs) are critical regulators of the tumor microenvironment. They exhibit diverse pro-tumorigenic and antitumor phenotypes depending on their monocyte-derived or tissue-resident origins. Beyond biochemical signaling, the mechanical properties of the tumor microenvironment, including extracellular matrix stiffness, density, architecture, and spatial heterogeneity, can regulate TAM behavior. This review discusses how these mechanical cues influence TAM infiltration, polarization, and tumor-supportive functions. We further highlight how spatially distinct mechanical environments contribute to TAM heterogeneity within solid tumors. Furthermore, we evaluate how advanced 3D biomimetic cancer platforms, including hydrogels, spheroids, organoids, and microfluidic organ-on-a-chip models, have become essential for accurately recapitulating these mechanoresponsive behaviors and phenotypic adaptations <i>in vitro</i>. We also discuss the capacity and current limitations of these models in reproducing the mechanical properties of the tumor microenvironment. Finally, we discuss how understanding these mechanical regulatory pathways may reveal promising avenues for TAM-targeted therapeutic strategies, particularly those aimed at disrupting mechanical niches to achieve effective TAM depletion or antitumor reprogramming. We highlight the need to integrate TAM-targeted strategies with mechanobiological regulation. Collectively, these insights underscore the importance of mechanobiology in regulating macrophage plasticity and its therapeutic potential in clinical oncology.</p>","PeriodicalId":12448,"journal":{"name":"Frontiers in Cell and Developmental Biology","volume":"14 ","pages":"1915582"},"PeriodicalIF":5.3,"publicationDate":"2026-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13627447/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149106749","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}