Journal of Cellular Physiology最新文献

{"title":"Revisiting Cell Death in Colorectal Cancer: The Rise of Ferroptosis as a Therapeutic Opportunity","authors":"Abaher O. Altamimi,&nbsp;Noha M. Elemam,&nbsp;Matthew F. Kalady,&nbsp;Iman M. Talaat","doi":"10.1002/jcp.70237","DOIUrl":"10.1002/jcp.70237","url":null,"abstract":"<div>\u0000 \u0000 <p>Colorectal cancer (CRC) remains a global health concern and a leading cause of cancer mortality, where therapeutic resistance persists as the central barrier to sustained response. Most conventional therapies rely on apoptosis, but CRC frequently resists through p53 alterations, anti-apoptotic BCL-2 upregulation, and drug efflux mechanisms. Here, we explore unconventional cell death pathways, focusing on ferroptosis, as a strategy to overcome apoptosis-dependent therapeutic resistance in CRC. We discussed the molecular mechanisms of ferroptosis, including GPX4 blockade, iron dysregulation, and lipid metabolism remodeling, and emphasized their implications for drug-resistant CRC. Then, necroptosis, pyroptosis, and autophagy were discussed in relation to their crosstalk with ferroptosis. Preclinical models show that ferroptosis inducers (e.g., erastin, RSL3, talaroconvolutin) selectively kill chemoresistant CRC, including KRAS-mutant CRC, and potentiate the efficacy of conventional regimens. The therapeutic duality of autophagy, pyroptosis, and necroptosis in CRC is discussed, with emphasis on ferroptosis's ability to circumvent traditional mechanisms of resistance. Yet, clinical translation is hindered by insufficient pharmacokinetics, systemic toxicity, limited biomarker availability, tumor heterogeneity, compensatory antioxidant pathways, and the need for safer delivery platforms. We propose that ferroptosis is most likely to enter CRC therapy through rational combinations, biomarker-guided patient selection, and tumor-targeted delivery platforms rather than as a stand-alone cytotoxic strategy.</p></div>","PeriodicalId":15220,"journal":{"name":"Journal of Cellular Physiology","volume":"241 10","pages":""},"PeriodicalIF":4.0,"publicationDate":"2026-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149171305","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Rev-erb-α in Skeletal Muscle Adaptation: Integrating Circadian Control Mechanisms and Exercise Dynamic Responses","authors":"Ivo Vieira de Sousa Neto,&nbsp;Alisson Luiz da Rocha,&nbsp;Ana Paula Pinto,&nbsp;Eliézer Lucas Pires Ramos,&nbsp;Eduardo Rochete Ropelle,&nbsp;José Rodrigo Pauli,&nbsp;Ellen Cristini de Freitas,&nbsp;Adelino Sanchez Ramos da Silva","doi":"10.1002/jcp.70239","DOIUrl":"10.1002/jcp.70239","url":null,"abstract":"<p>Circadian rhythms orchestrate a host of biological processes in a time-dependent manner to maintain homeostasis in response to exercise. Within this framework, Rev-erb-α, an intracellular nuclear receptor and transcriptional regulator, transcends its role in circadian rhythms to drive myogenesis, muscle remodeling, primary metabolism, and autophagy, underscoring its versatile, pleiotropic actions. This review consolidates experimental evidence from cell culture, genetically modified animal models, drug-based approaches and humans, highlighting the role of Rev-erb-α mechanisms in skeletal muscle and exercise adaptation. Recent frontier-of-knowledge data indicate that acute and chronic exercise elicit distinct Rev-erb-α signatures. There is bimodal regulation: Rev-erb-α is downregulated immediately post-exercise, followed by a subsequent increase, reflecting its primary role in pathway repression. In chronic conditions, the upregulation of Rev-erb-α can act as an adaptive mechanism that governs robust responses to energy demand and mitochondrial function, thereby coordinating the metabolic network, calcium homeostasis, and oxidative capacity. Also, Rev-erb-α overexpression or its pharmacological activation may reduce pathways associated with muscle atrophy, thereby preserving tissue function and muscle mass. Excitingly, higher physical activity levels increase the amplitude of Rev-erb-α over 24 h, enhancing health and performance. However, exercise timing determines the Rev-erb-α signature that affects downstream phenotypes in skeletal muscle. Thus, elucidating the mechanisms of regulation and action of the Rev-erb-α protein may offer new perspectives for improving or preserving muscle quality across different health conditions and diseases.</p>","PeriodicalId":15220,"journal":{"name":"Journal of Cellular Physiology","volume":"241 10","pages":""},"PeriodicalIF":4.0,"publicationDate":"2026-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jcp.70239","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149136770","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":"Sestrin1 Ameliorates Senescence and Mediates the Protective Effects of Exercise Against Hepatic Abnormality in C57BL/6J Mice","authors":"Xuege Yang,&nbsp;Yuchen Zou,&nbsp;Xiuru Li,&nbsp;Zhili Rong,&nbsp;Yanmei Niu,&nbsp;Li Fu","doi":"10.1002/jcp.70241","DOIUrl":"10.1002/jcp.70241","url":null,"abstract":"<div>\u0000 \u0000 <p>Liver aging is characterized by structural remodeling and functional decline, frequently driven by mitochondrial dysfunction and senescence-associated secretory phenotype (SASP). Sestrins (SESNs) are a family of stress-inducible proteins, among which Sestrin1 and Sestrin2 are crucial for maintaining metabolic and redox homeostasis, yet their specific involvement in hepatic senescence remains unclear. In the present study, in vivo experiments were performed using WT mice at young, middle, and old ages, together with aged Sestrin1^−/− and Sestrin2^−/− mice. The aged mice displayed multifaceted hepatic dysfunction, accompanied by a progressive, age-dependent decline of hepatic Sestrin1 and Sestrin2 expression. Intriguingly, hepatic cellular senescence, lipid deposition, oxidative stress and inflammation were significantly exacerbated in Sestrin1^-/- mice compared to Sestrin2^-/- and WT mice. To further explore the underlying mechanism, senescent AML12 cells overexpressing Sestrin1 were treated with or without mitochondrial division inhibitor-1 (Mdivi-1). Mechanistically, Sestrin1 preserved mitochondrial homeostasis by promoting mitochondrial fission via dynamin-related protein 1 (Drp1), a master regulator of mitochondrial fission, and curtailing the leakage of mitochondrial DNA (mtDNA) into the cytoplasm, profoundly suppressing the cGAS-STING pathway. However, these effects were abolished upon mitochondrial fission inhibition. Given that exercise training is a potent anti-aging strategy known to upregulate SESNs protein levels, we further demonstrated that Sestrin1 is indispensable for its hepatoprotective benefits. Collectively, our results identified that the Sestrin1/Drp1/cGAS-STING axis plays a pivotal role in liver aging and positioned Sestrin1 as a vital therapeutic target, serving as a key mediator of the anti-aging benefits of exercise training.</p></div>","PeriodicalId":15220,"journal":{"name":"Journal of Cellular Physiology","volume":"241 10","pages":""},"PeriodicalIF":4.0,"publicationDate":"2026-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149127631","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Electrical Pulse Stimulation Partially Restores Insulin Signaling in Palmitate-Induced Insulin-Resistant Skeletal Muscle Cells via Mitochondrial Remodeling and Contractile Activity-Dependent Secretome","authors":"Falcone Alessandro,&nbsp;Yilmaz Sevgican,&nbsp;Hendlinger Mona,&nbsp;Schrauwen Patrick,&nbsp;Lipaeva Polina,&nbsp;Piribauer Marlene,&nbsp;Heilmann Geronimo,&nbsp;Trenkamp Sandra,&nbsp;Roden Michael,&nbsp;Mastrototaro Lucia","doi":"10.1002/jcp.70240","DOIUrl":"10.1002/jcp.70240","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 <p>Lipid oversupply induces insulin resistance in skeletal muscle (SkM), partly by altering mitochondrial function and dynamics. Although electrical pulse stimulation (EPS) improves insulin signaling in myotubes, the mechanisms contributing to this effect under lipotoxic conditions remain unclear. Thus, we investigated whether EPS restores lipid-induced insulin resistance in association with changes in mitochondrial respiration and dynamics, lipotoxic intermediates and evaluated the contribution of contraction-induced secreted factors, including small extracellular vesicles (sEV). Murine C2C12 myotubes were treated with palmitate (PA, 0.3 mmol/l) and subjected to EPS (1 Hz, 11.5 V) for 24 h. Insulin signaling, mitochondrial dynamics, respiratory capacity and lipotoxic intermediates were assessed by Western blotting, high-resolution respirometry and liquid chromatography-tandem mass spectrometry in control (CON) and PA-treated cells before and after EPS. Additionally, CON and PA-treated cells were incubated for 24 h with conditioned media and sEV from unstimulated or EPS-stimulated CON and PA-treated cells to evaluate the effect of the myocellular secretome on AKT signaling. PA reduced insulin-stimulated AKT(Ser473) and (Thr308) phosphorylation, which was partially rescued by EPS. In PA cells, EPS decreased the fusion proteins mitofusin 1 and 2 (MFN1, MFN2) and increased the fission marker dynamin-related protein 1 (DRP1). However, mitochondrial respiration and lipid accumulation were unaffected by EPS. Furthermore, conditioned media and sEV from EPS-stimulated cells enhanced AKT phosphorylation in PA-treated cells. These findings demonstrate that attenuation of lipid-induced insulin resistance is independent of mitochondrial respiratory capacity and lipid accumulation, but it is associated with alterations in proteins involved in mitochondrial dynamics and is likely mediated by exercise-derived sEV.</p>\u0000 </section>\u0000 </div>","PeriodicalId":15220,"journal":{"name":"Journal of Cellular Physiology","volume":"241 10","pages":""},"PeriodicalIF":4.0,"publicationDate":"2026-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13640965/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149110156","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":"SLC35F2 in Cancer Development and Progression","authors":"Si Shen,&nbsp;Zhonghao Tang,&nbsp;Chen Guo,&nbsp;Sixi Li,&nbsp;Anjie Chen,&nbsp;Chenwei Gu,&nbsp;Yuanyuan Mi","doi":"10.1002/jcp.70238","DOIUrl":"10.1002/jcp.70238","url":null,"abstract":"<div>\u0000 \u0000 <p>Solute carrier family 35 member F2 (SLC35F2) is a transporter located predominantly at the plasma membrane and Golgi apparatus and is predicted to contain ten transmembrane helices. Recent studies have identified SLC35F2 as the only currently known queuosine (Q)-specific transporter in human cells and as the principal high-affinity transporter of queuine (q), although it is not the absolutely exclusive route for q uptake. SLC35F2 is also aberrantly expressed in multiple cancers and has been associated with cell proliferation, migration, invasion, chemoresistance, and ferroptosis regulation. However, the available evidence derives mainly from database analyses, individual cell-based studies, and limited animal experiments and does not yet demonstrate that its tumor-promoting effects directly depend on q/Q uptake or tRNA queuosine modification. SLC35F2 is also an important uptake transporter for the anticancer agent YM155, and its expression can influence intracellular drug exposure and DNA-damage toxicity. YM155 was initially classified as a survivin transcriptional inhibitor, but subsequent studies indicate that its actions also involve DNA intercalation and oxidative DNA damage. Previous clinical trials did not prospectively stratify patients by SLC35F2 expression and showed limited overall efficacy; consequently, its clinical value remains translationally uncertain and biomarker-dependent. Using a structured narrative-review approach, this article critically evaluates the structure and localization of SLC35F2, q/Q transport, regulation of its expression and protein stability, tumor-associated functions, and YM155 delivery. It distinguishes replicated mechanisms from findings supported by single studies and from testable hypotheses, thereby providing a framework for future mechanistic research and precision drug delivery.</p></div>","PeriodicalId":15220,"journal":{"name":"Journal of Cellular Physiology","volume":"241 10","pages":""},"PeriodicalIF":4.0,"publicationDate":"2026-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149110285","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction to “Exosome-Mediated Transfer of miR-1260b Promotes Cell Invasion Through Wnt/β-catenin Signaling Pathway in Lung Adenocarcinoma”","authors":"","doi":"10.1002/jcp.70229","DOIUrl":"10.1002/jcp.70229","url":null,"abstract":"<p>Yang Xia, et al. Exosome-mediated transfer of miR-1260b promotes cell invasion through Wnt/β-catenin signaling pathway in lung adenocarcinoma. J Cell Physiol. 2020 Oct;235(10):6843-6853.</p><p>In Figure 1c, western blot image of Calnexin was incorrect. This error occurred during the revision stage, not the initial submission. We mistakenly submitted the unmarked version of Figure 1 instead of the revised one. The revised Figure 1 is provided below. The authors confirm that this mistake does not affect the results and conclusions of the study.</p><p>We apologize for this error.</p>","PeriodicalId":15220,"journal":{"name":"Journal of Cellular Physiology","volume":"241 10","pages":""},"PeriodicalIF":4.0,"publicationDate":"2026-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jcp.70229","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149110178","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":"Hepatic Macrophage STING Signaling in Liver Fibrosis: Mechanisms and Therapeutic Perspectives.","authors":"Qiulian Lei, Xinghong Liu, Yidan Yuan, Hui Li","doi":"10.1002/jcp.70235","DOIUrl":"https://doi.org/10.1002/jcp.70235","url":null,"abstract":"<p><p>Liver fibrosis (LF) arises from chronic liver injury, in which a persistently pro-inflammatory microenvironment shaped by hepatic macrophages drives hepatic stellate cells (HSCs) activation and fibrosis progression. The cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) pathway serves as a molecular hub linking metabolic liver injury to immune and inflammatory responses, sensing danger signals from metabolic stress, mitochondrial injury, and cell death to initiate downstream inflammatory transcription. This signaling may sustain a pro-inflammatory macrophage phenotype and amplify inflammation, potentially driving fibrosis from reversible repair toward progressive disease. This review summarizes the pathological mechanisms and translational advances of macrophage STING signaling in LF, discusses how STING integrates mitochondrial DNA (mtDNA) sensing with non-canonical metabolic stress signals to sustain pro-inflammatory macrophage states via bioenergetic and organelle remodeling, and evaluates emerging therapeutic strategies aimed at modulating macrophage STING signaling, including mesenchymal stem cell (MSC)/exosome-based approaches and natural-product interventions, for the potential therapeutic management of LF.</p>","PeriodicalId":15220,"journal":{"name":"Journal of Cellular Physiology","volume":"241 10","pages":"e70235"},"PeriodicalIF":4.0,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149216313","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Molecular and Cellular Underpinnings of Primary Hypertension: An Integrative Mechanistic Framework","authors":"Dima Nasrallah,&nbsp;Alaa Abdelhamid,&nbsp;Omar Tluli,&nbsp;Yaman Al-Haneedi,&nbsp;Mera Abu Hussien,&nbsp;Ali H. Eid","doi":"10.1002/jcp.70233","DOIUrl":"https://doi.org/10.1002/jcp.70233","url":null,"abstract":"<p>Hypertension is a highly prevalent clinical condition and a major contributor to global cardiovascular morbidity and mortality. Despite extensive research, its complex and multifaceted pathogenesis is yet to be fully elucidated. This paper explores the updated understanding of primary hypertension as a systemic disorder rather than an isolated vascular or renal abnormality. At the center of this multifactorial disease lie three primary and interrelated pathophysiological mechanisms: dysregulation of the renin–angiotensin–aldosterone system, dysfunction of the central nervous system, and activation of inflammatory and oxidative stress pathways. These core drivers not only interact with each other in a self-reinforcing cycle but also serve as convergence points for a range of additional contributors. Specifically, suboptimal dietary patterns, salt sensitivity, gut microbiota dysbiosis, circadian rhythm disruption, and insulin resistance act by modulating these central processes, thereby perpetuating blood pressure elevation. This review further elaborates on how these mechanisms span across multiple organ systems, driving vascular, renal, neurohumoral, and immune dysfunction. Taken together, this perspective underscores the need for integrated, upstream-targeted therapeutic strategies. By highlighting the interconnected nature of these drivers and contributors, this paper provides a comprehensive framework to inform future research and guide more effective preventive and management approaches for hypertension.</p>","PeriodicalId":15220,"journal":{"name":"Journal of Cellular Physiology","volume":"241 10","pages":""},"PeriodicalIF":4.0,"publicationDate":"2026-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jcp.70233","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149068469","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":"RETRACTION: Loss of TET1 Facilitates DLD1 Colon Cancer Cell Migration via H3K27me3-Mediated Down-Regulation of E-Cadherin","authors":"","doi":"10.1002/jcp.70223","DOIUrl":"10.1002/jcp.70223","url":null,"abstract":"<p><b>RETRACTION</b>: Z. Zhou, H.-S. Zhang, Y. Liu, Z.-G. Zhang, G.-Y. Du, H. Li, X.-Y. Yu, and Y.-H. Huang, “Loss of TET1 Facilitates DLD1 Colon Cancer Cell Migration via H3K27me3-Mediated Down-Regulation of E-Cadherin,” <i>Journal of Cellular Physiology</i> 233, no. 2 (2018): 1359–1369, https://doi.org/10.1002/jcp.26012.</p><p>The above article, published online on 17 May 2017 in Wiley Online Library (https://onlinelibrary.wiley.com/), has been retracted by agreement between the journal Editor-in-Chief, Robert Heath; and Wiley Periodicals LLC. The retraction has been agreed due to concerns raised by a third party on PubPeer [1], which revealed inappropriate figure overlaps and suspected image manipulations in Figure 1c among the three columns; Figure 2c partial overlaps within the images shTET1(1) and shTET1(2); and partial overlaps within the images Figure 6b EZH2 and siUTX-1. In addition, concerns were raised about all Western blots in the article, specifically, that the background appears to be very bright due to overly adjusted contrast. Although the corresponding author was responsive and provided a correction of overlapped figures and also shared the original Western blots during the investigation, the Editor-in-Chief and the publisher have decided that a correction could not resolve the concerns raised for this paper. Therefore, the Editor-in-Chief has lost faith in the reliability of the presented results, and the article must be retracted. The authors disagree with the retraction.</p><p><b>References</b></p><p>[1] S. consimilis, “Loss of TET1 facilitates DLD1 colon cancer cell migration via H3K27me3-mediated down-regulation of E-cadherin,” PubPeer, 2024, https://pubpeer.com/publications/FE83376A7CF1DA6D632CA15B7219AE.</p>","PeriodicalId":15220,"journal":{"name":"Journal of Cellular Physiology","volume":"241 9","pages":""},"PeriodicalIF":4.0,"publicationDate":"2026-09-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jcp.70223","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149061346","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":"Early-Life Nutritional Disruption Reshapes Gastric Epithelial Development Through Coordinated Changes in the Dynamics and Signaling of Proliferative Niches","authors":"Isadora Campos Rattes,&nbsp;Marcos Aurélio Santos da Costa,&nbsp;Viviane Rosa de Oliveira,&nbsp;Patrícia Gama","doi":"10.1002/jcp.70234","DOIUrl":"10.1002/jcp.70234","url":null,"abstract":"<p>Gastric gland cells originate from two proliferative niches: the main rapid one in the isthmus, and the slow secondary one in the base. However, while nutrition is dependent on breastfeeding, the proliferative niches are not established, and proliferation occurs along the gland. Currently, we investigated the influence of early weaning (EW) on shaping gastric proliferative niches and their signaling. Wistar rats were separated into suckling (S) and EW groups on postnatal day (PND) 15 for gastric mucosa collection. BrdU was administered (PND 14 and 15) and as it diluted between daughter-cells we evaluated migration and differentiation. In parallel EdU incorporation was used to identify cells during S phase. Through these tools, we studied the different profiles of BrdU/EdU dual labeling at 18, 21 and 30 PND. At 18 PND, EW decreased BrdU+ population (<i>p</i> &lt; 0.0001 <i>vs</i>. S group) in the upper and bottom gland areas (<i>p</i> &lt; 0.05). The BrdU + /EdU+ cells were concentrated in the upper gland, where we recorded a larger EdU+ population after EW (<i>p</i> &lt; 0.05). On PND 30, EW decreased BrdU+ cells in the gland (<i>p</i> &lt; 0.05), whereas EdU+ cells were more numerous in the isthmus. At 18 PND, EW reduced <i>Wnt3</i>, <i>Notch1</i>, and <i>Notch2</i> expressions (<i>p</i> &lt; 0.05), while increasing <i>Bmp2</i>. In contrast, at 60 PND, <i>Axin2</i>, <i>Notch1</i>, and <i>Notch2</i> transcripts were elevated after EW (<i>p</i> &lt; 0.05). Notch1 and Notch2 distribution indicated that EW might shift Notch2 to the upper gland, potentially affecting the fate of progenitor cells in pups. <i>In silico</i> analyses showed that zymogenic cells are in a renewal-promoting environment, while parietal cells contribute to differentiation and signaling. Therefore, EW restricted the proliferative activity to the isthmus, altering the spatiotemporal expression of genes involved in stemness and differentiation, and reshaped the distribution of Notch receptors, without affecting the distribution of its downstream effector Hes1. These spatially organized molecular landscapes are crucial for proper epithelial renewal and function, and our data suggest that early nutritional disruption reprograms these niches with long-term consequences.</p>","PeriodicalId":15220,"journal":{"name":"Journal of Cellular Physiology","volume":"241 9","pages":""},"PeriodicalIF":4.0,"publicationDate":"2026-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jcp.70234","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149038907","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}