Cell and Bioscience最新文献

{"title":"Single-cell RNA sequencing uncovers abnormal Sertoli-cell elevation and testicular niche impairment in the transfemales's testis.","authors":"Jun Yu, Longfei Hu, Huixia Li, Xiaofeng Li, Chaoye Ma, Ting Jiang, Yongxin Liu, Xue Wang, Xia Li, Liandong Zuo, Haocheng Lin, Wenming Xu, Yiwen Zhou, Yang Liu, Hao Chen","doi":"10.1186/s13578-025-01445-3","DOIUrl":"10.1186/s13578-025-01445-3","url":null,"abstract":"<p><strong>Background: </strong>Transgender women (transfemales) often undergo gender-affirming hormone therapy (GAHT). However, the testicular impacts of feminising hormones present heterogeneity due to the complexity of testicular regulatory mechanisms.</p><p><strong>Method: </strong>In this study, we analyzed approximately 49,385 single-cell transcriptomes from transfemale human testicular tissue, comparing cellular composition with that of cisgender male individuals across a range of ages. Our approach included clustering of cell types, identification of marker genes, pseudotime analysis of germ cells, and comprehensive cell-cell interaction analyses. We employed immunohistochemistry, quantitative real-time PCR, and immunostaining to validate the key molecular signatures identified in the pathways of interest.</p><p><strong>Results: </strong>GAHT led to a significant reduction in spermatogenic cells, accompanied by an unexpected increase in Sertoli cell numbers per seminiferous tubule, suggesting disrupted germ cell-Sertoli cell interactions. Molecular analyses revealed upregulation of genes such as Decorin (DCN), Myoglobin (MB), and Beta-2-Microglobulin (B2M) in Sertoli cells, with enrichment in pathways related to cell adhesion, cytokine response, and wnt signaling. Notably, β-catenin was significantly elevated and translocated into the nucleus of Sertoli cells determined by immunostaining analysis. Additionally, collagen fiber infiltration disrupted the testicular microenvironment, further impairing germline-Sertoli cell communication.</p><p><strong>Conclusion: </strong>This study provides novel insights into the testicular alterations associated with GAHT in transfemales, particularly highlighting the role of germline-Sertoli cell interactions in testicular injury. Our findings contribute to a deeper understanding of the testicular response to feminizing hormones, offering a foundation for future therapeutic strategies.</p>","PeriodicalId":49095,"journal":{"name":"Cell and Bioscience","volume":"15 1","pages":"106"},"PeriodicalIF":6.1,"publicationDate":"2025-07-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12276673/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144676268","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":"Circ_HUWE1: a novel regulator of lipid accumulation, inflammation, and gut microbiota in atherosclerosis.","authors":"Zulong Sheng, Yi Fan, Zhenjun Ji, Yanru He, Rui Zhang, Yuyu Yao, Genshan Ma","doi":"10.1186/s13578-025-01440-8","DOIUrl":"10.1186/s13578-025-01440-8","url":null,"abstract":"<p><strong>Background: </strong>Atherosclerosis (AS) is a chronic cardiovascular disease characterized by lipid accumulation and inflammation within arterial walls, leading to plaque formation and cardiovascular events. Circular RNAs (circRNAs) have emerged as key regulators in various diseases, but their role in AS remains poorly understood. This study investigates the protective role and underlying mechanism of circ_HUWE1 in lipid metabolism, macrophage infiltration, inflammation, and gut microbiota modulation in AS.</p><p><strong>Methods: </strong>Circ_HUWE1 expression was evaluated in coronary artery disease (CAD) patients and in fecal samples from AS patients. An ApoE^-/- mouse model of high-fat diet (HFD)-induced atherosclerosis was employed to assess functional role of circ_HUWE1. Circ_HUWE1 overexpression was induced via adeno-associated virus delivery, and the impact on lipid accumulation, macrophage infiltration, inflammation, and gut microbiota composition was analyzed. Vascular smooth muscle cells (VSMCs) were used for in vitro studies of circ_HUWE1 mechanism of action, including interactions with miR-143-3p and IGFBP5.</p><p><strong>Results: </strong>Circ_HUWE1 expression was significantly downregulated in CAD patients, fecal samples of AS patients and in HFD-fed ApoE^-/- mice. Circ_HUWE1 overexpression reduced lipid accumulation, plaque formation, and macrophage infiltration in ApoE^-/- mice. Circ_HUWE1 also mitigated dyslipidemia by lowering serum levels of triglycerides (TG), total cholesterol (TC), and low-density lipoprotein (LDL) while increasing high-density lipoprotein (HDL) levels. Histological analyses showed attenuation of hepatocyte steatosis and adipose tissue enlargement in HFD-fed ApoE^-/- mice. Additionally, circ_HUWE1 reduced proinflammatory cytokines and adhesion molecules, highlighting its anti-inflammatory properties. Furthermore, circ_HUWE1 also modulated the gut microbiota by restoring the abundance of beneficial gut bacteria, Faecalibacterium prausnitzii and Coprococcus comes, which correlated with reduced plaque burden. Mechanistically, circ_HUWE1 functioned as a competing endogenous RNA (ceRNA) by sponging miR-143-3p, thereby upregulating IGFBP5 expression. In vitro, circ_HUWE1 suppressed lipid accumulation and inflammation in VSMCs, effects that were reversed by miR-143-3p overexpression and IGFBP5 knockdown.</p><p><strong>Conclusion: </strong>Our study demonstrates for the first time that circ-HUWE1 exerts a protective effect against atherosclerosis by regulating lipid metabolism, macrophage infiltration and inflammatory responses through the miR-143-3p/IGFBP5 axis and reshaping the gut microbiota. These findings suggest circ_HUWE1 as a potential therapeutic target for atherosclerosis treatment.</p>","PeriodicalId":49095,"journal":{"name":"Cell and Bioscience","volume":"15 1","pages":"105"},"PeriodicalIF":6.1,"publicationDate":"2025-07-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12275453/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144668753","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":"Reactive oxygen species regulate adipose-osteogenic lineage commitment of human mesenchymal stem cells by modulating gene expression of C/EBP homology protein and aldo-keto reductase family 1 member A1.","authors":"Chen Hao Chiang, Yu-Chieh Kao, Yi-Hui Lin, Yi-Shing Ma, Yu-Ting Wu, Bo-Yan Jian, Yau-Huei Wei, Chuan-Mu Chen, Ying-Ming Liou","doi":"10.1186/s13578-025-01448-0","DOIUrl":"10.1186/s13578-025-01448-0","url":null,"abstract":"<p><strong>Background: </strong>Bone-derived mesenchymal stem cells (BMSCs) are multipotent stem cells capable of differentiating into adipocytes and osteoblasts. Dysfunctional differentiation, characterized by a shift from osteoblastogenesis to adipogenesis, is closely associated with metabolic and senile osteoporosis. The Aldo-keto reductase family 1 member A1 (Akr1A1) enzyme, which utilizes NADPH to reduce aldehyde groups to alcohols, has emerged as a potential regulator. This study investigates the role of reactive oxygen species (ROS) in modulating Akr1A1 expression during the lineage differentiation of human mesenchymal stem cells into osteoblasts and adipocytes.</p><p><strong>Results: </strong>Our findings demonstrate that increased ROS levels enhance the expression of C/EBP homology protein (CHOP) and Akr1A1 during adipogenic differentiation. Conversely, reduced ROS levels suppress CHOP and Akr1A1 expression in osteogenically committed cells. Functional studies involving Akr1A1 silencing and overexpression revealed that Akr1A1 expression levels dictate MSC lineage commitment without altering ROS production or CHOP expression. Knockdown of Akr1A1 suppressed adipogenesis while promoting osteoblastogenesis, accompanied by upregulation of SIRT1, PGC-1α, TAZ, and other osteogenic transcription factors. In contrast, overexpression of Akr1A1 reduced SIRT1, PGC-1α, and TAZ levels, thereby enhancing adipogenesis and inhibiting osteogenesis. These findings position Akr1A1 as a downstream target of the ROS/CHOP signaling pathway. Using an oxidative stress cell model induced by D-galactose in BMSCs, we confirmed that elevated ROS levels upregulate CHOP and Akr1A1 expression, preferentially driving differentiation into adipocytes over osteoblasts.</p><p><strong>Conclusions: </strong>Our results reveal that intracellular ROS modulate CHOP and Akr1A1 expression, which regulate commitment to adipogenic and osteogenic lineages. This regulation appears to occur through inhibiting SIRT1-dependent pathways, shedding light on potential therapeutic targets for metabolic and age-related osteoporosis.</p>","PeriodicalId":49095,"journal":{"name":"Cell and Bioscience","volume":"15 1","pages":"104"},"PeriodicalIF":6.1,"publicationDate":"2025-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12275293/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144668754","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 dual role of mTOR signaling in lung development and adult lung diseases.","authors":"Jiahui Bao, Wenjing Bao, Yajie Song, Zhiliang Li, Liang Kan, Jianhua Fu, Dan Zhang","doi":"10.1186/s13578-025-01428-4","DOIUrl":"10.1186/s13578-025-01428-4","url":null,"abstract":"","PeriodicalId":49095,"journal":{"name":"Cell and Bioscience","volume":"15 1","pages":"103"},"PeriodicalIF":6.2,"publicationDate":"2025-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12273038/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144660872","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 sequencing combined with spatial transcriptomics reveals the characteristics of follicle-targeted inflammation patterns in primary cicatricial alopecia.","authors":"Qitao Chen, Yuqian Li, Qilin Zhu, Zhongming Li, Guanghui Shao, Yanjun Liu, Peixuan Jiang, Qiuwei Tao, Lili Shen, Jing Zhu, Linwei Wei, Yanhua Li, Xufeng Du","doi":"10.1186/s13578-025-01447-1","DOIUrl":"10.1186/s13578-025-01447-1","url":null,"abstract":"<p><strong>Background: </strong>Primary cicatricial alopecia (PCA) causes irreversible hair loss due to immune-mediated hair follicle destruction. This study investigates follicle-targeted inflammation in lichen planopilaris (LPP), a major PCA subtype, to identify therapeutic targets.</p><p><strong>Methods: </strong>Scalp samples from LPP, localized scleroderma (LS), and controls were analyzed using single-cell RNA sequencing and spatial transcriptomics. Cellular composition, spatial localization, and intercellular interactions were examined using differential gene expression and ligand-receptor analyses.</p><p><strong>Results: </strong>CD8⁺ effector memory T cells (Tem) and macrophages infiltrated hair follicles in LPP, disrupting immune privilege and promoting scarring. Heightened interferon-γ (IFN-γ) signaling and STAT1 activation in Tem cells caused epithelial-mesenchymal transition (EMT) in hair follicle stem cells (HFSCs). Additionally, macrophage-secreted oncostatin M (OSM) impaired HFSC integrity. These mechanisms drive LPP's inflammation and fibrosis.</p><p><strong>Conclusions: </strong>Our findings identify interferon-γ and oncostatin M as key drivers of LPP pathogenesis, offering targets to reduce follicular scarring and preserve hair growth.</p><p><strong>Trial registration: </strong>Not applicable.</p>","PeriodicalId":49095,"journal":{"name":"Cell and Bioscience","volume":"15 1","pages":"102"},"PeriodicalIF":6.1,"publicationDate":"2025-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12265327/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144650968","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":"Cell condensation initiates organogenesis: the role of actin dynamics in supracellular self-organizing process.","authors":"Jun-Xi He, Bing-Dong Sui, Yan Jin, Chen-Xi Zheng, Fang Jin","doi":"10.1186/s13578-025-01429-3","DOIUrl":"10.1186/s13578-025-01429-3","url":null,"abstract":"<p><p>The emergence of complex tissue architectures from homogeneous stem cell condensates persists as a central enigma in developmental biology. While biochemical signaling gradients have long dominated explanations of organ patterning, the mechanistic interplay between tissue-scale forces and thermodynamic constraints in driving symmetry breaking remains unresolved. This review unveils supracellular actin networks as mechanochemical integrators that establish developmental tensegrity structures, wherein Brownian ratchet-driven polymerization generates patterned stress fields to guide condensate stratification. Central to this paradigm is the dynamic remodeling of actin branches, which transduce mechanical loads into adaptive network architectures through force-modulated capping kinetics and angular reorientation. Such plasticity enables fluid-to-solid phase transitions, stabilizing organ primordia through viscoelastic microdomain formation. Crucially, these biophysical processes are functionally coupled with metabolic reprogramming events, where cytoskeletal strain modulates glycolytic flux and nuclear mechanotransduction pathways to inform differentiation decisions, forging a feedback loop between tissue mechanics and cellular fate specification. Building on these insights, we argue that limitations in current organoid self-organization may originate from incomplete reconstitution of actin-mediated mechanical coherence, and modeling of heterogeneous mesenchymal condensation dynamics offers a strategic framework to decode self-organization trajectories, bridging developmental principles with regenerative design. By synthesizing advances from molecular biophysics to tissue mechanics, this work reframes organogenesis not as a hierarchy of molecular commands, but as an emergent continuum where biochemical, mechanical, and thermodynamic constraints coevolve to sculpt living architectures.</p>","PeriodicalId":49095,"journal":{"name":"Cell and Bioscience","volume":"15 1","pages":"101"},"PeriodicalIF":6.1,"publicationDate":"2025-07-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12257841/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144627490","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":"HTT loss-of-function contributes to RNA deregulation in developing Huntington's disease neurons.","authors":"Emilia Kozłowska, Agata Ciołak, Grażyna Adamek, Julia Szcześniak, Agnieszka Fiszer","doi":"10.1186/s13578-025-01443-5","DOIUrl":"10.1186/s13578-025-01443-5","url":null,"abstract":"<p><strong>Background: </strong>Huntington's disease (HD) is a neurodegenerative disorder caused by the expansion of CAG repeats in the HTT gene, which results in a long polyglutamine tract in the huntingtin protein (HTT). One of the earliest key molecular mechanisms underlying HD pathogenesis is transcriptional dysregulation, which is already present in the developing brain. In this study, we searched for networks of deregulated RNAs crucial for initial transcriptional changes in HD- and HTT-deficient neuronal cells.</p><p><strong>Results: </strong>RNA-seq (including small RNAs) was used to analyze a set of isogenic human neural stem cells. The results were validated using additional methods, rescue experiments, and in the medium spiny neuron-like cells. We observed numerous changes in gene expression and substantial dysregulation of miRNA expression in HD and HTT-knockout (HTT-KO) cell lines. The overlapping set of genes upregulated in both HD and HTT-KO cells was enriched in genes associated with DNA binding and the regulation of transcription. We observed substantial upregulation of the following transcription factors: TWIST1, SIX1, TBX1, TBX15, MSX2, MEOX2 and FOXD1. Moreover, we identified miRNAs that were consistently deregulated in HD and HTT-KO cells, including miR-214, miR-199, and miR-9. These miRNAs may function in the network that regulates TWIST1 and HTT expression via a regulatory feed-forward loop in HD.</p><p><strong>Conclusions: </strong>On the basis of overlapping changes in the mRNA and miRNA profiles of HD and HTT-KO cell lines, we propose that transcriptional deregulation in HD at early neuronal stages is largely caused by a deficiency of properly functioning HTT rather than a typical gain-of-function mechanism.</p>","PeriodicalId":49095,"journal":{"name":"Cell and Bioscience","volume":"15 1","pages":"100"},"PeriodicalIF":6.2,"publicationDate":"2025-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12239503/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144601992","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 role of m⁶A RNA methylation in a love-hate relationship between porcine rotavirus and host cells.","authors":"Yaxu Liang, Xuejiao Zhu, Ruhao Zhuo, Ning Peng, Shuyu Chen, Shimeng Huang, Zhending Gan, Jun Qi, Zhibo Wang, Bin Li, Xiang Zhong","doi":"10.1186/s13578-025-01436-4","DOIUrl":"10.1186/s13578-025-01436-4","url":null,"abstract":"<p><p>N6-methyladenosine (m⁶A), the most abundant mRNA modification, regulates various mRNA metabolism to affect numerous physiological processes, including immune response. Interestingly, many RNA viruses contain internal m⁶A modifications that contribute to viral replication and innate immune escape process, but its mechanisms remain unclear. Porcine rotavirus (PoRV) is a common cause of diarrhea and gastroenteritis in piglets. Here, we first revealed the m⁶A methylation profile on the PoRV genome. PoRV infection significantly reduced methyltransferase METTL3 expression and induced nuclear-cytoplasmic translocation of METTL3. The structural protein VP6 of PoRV can co-localize with METTL3 in the cytoplasm and bind to METTL3 protein, suggesting that PoRV hijacked the host METTL3 to achieve m⁶A methylation. On the contrary, knockdown of Mettl3 or Ythdf2 in IPEC cells inhibited the replication of PoRV. Mechanistically, silencing of Mettl3 or Ythdf2 enhanced the expression of IRF2 and IFI44L via an increase of mRNA stability of Irf2 and Ifi44l. Furthermore, knockdown of Irf2 and Ifi44l promoted viral replication in IPEC cells. In conclusion, PoRV took full advantage of METTL3 to promote replication, in turn, host reduced own m⁶A methylation to enhance IRF2 and IFI44L to restrain virus infection, suggesting a love-hate relationship between virus and host, and providing novel targets for developing antiviral drugs in the pig industry.</p>","PeriodicalId":49095,"journal":{"name":"Cell and Bioscience","volume":"15 1","pages":"99"},"PeriodicalIF":6.1,"publicationDate":"2025-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12239464/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144592787","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":"Cerebrovascular-mediated dynamic alterations in neurovascular coupling: a key pathological mechanism of depression.","authors":"Xiaoyun Yang, Jiaxin Wang, Jiahao Zhang, Mengjie Zhang, Anran Hao, Feng Guo, Xueying Huang, Jinlan Yan, Yuanjia Zheng, Yucen Xia, Taiyi Wang, Meng Zhang, Ning Weng, Yongjun Chen, Lin Yao","doi":"10.1186/s13578-025-01444-4","DOIUrl":"10.1186/s13578-025-01444-4","url":null,"abstract":"<p><p>Neurovascular coupling (NVC) is a vital regulatory mechanism that synchronizes neural activity with vascular responses to support brain function. Although the precise mechanisms of NVC remain incompletely elucidated, its dysfunction is increasingly implicated in the pathogenesis of various neurological disorders. This review synthesizes recent advancements in understanding the vascular cascade, emphasizing key dynamic regulators of NVC, including mechanical forces and diffusible signals mediated by blood flow. We explore the intricate bidirectional interactions between the vasculature and neurons, highlighting their interdependent roles in neurovascular regulation. Using major depressive disorder (MDD) as a case study, we further discuss emerging evidence linking vascular dysfunction and impaired NVC to MDD pathophysiology. These insights position NVC as a promising therapeutic target for emotional disorders, underscoring the pivotal roles of hemodynamic signaling in neurovascular regulation.</p>","PeriodicalId":49095,"journal":{"name":"Cell and Bioscience","volume":"15 1","pages":"97"},"PeriodicalIF":6.1,"publicationDate":"2025-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12232600/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144585462","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":"Regulation of revival stem cell differentiation by CREPT/RPRD1B during intestinal regeneration.","authors":"Tingwei Lan, Mengdi Li, Xiaolin Duan, Huihui Jia, Yajun Cao, Yinyin Wang, Fangli Ren, Jianqiu Sheng, Junfeng Xu, Zhijie Chang","doi":"10.1186/s13578-025-01434-6","DOIUrl":"10.1186/s13578-025-01434-6","url":null,"abstract":"<p><p>Revival stem cells (revSCs) defined by transient induction of clusterin (CLU) expression rapidly expand and differentiate into multiple IEC lineages during intestinal regeneration. Although revSC induction is well-studied, the mechanisms governing their differentiation remain unclear. In this study, we demonstrate that CREPT/RPRD1B, a protein highly expressed in tumors and essential for crypt-base columnar cell (CBC) maintenance, was required for revSC differentiation during intestinal regeneration. Using Villin-Cre-mediated CREPT knockout (Vil-CREPT^KO) mice, we found that CREPT deletion leads to regeneration failure following irradiation-induced damage. Interestingly, revSCs were remarkably accumulated, but enterocytes were decreased in Vil-CREPT^KO mice. Our single-cell transcriptome analyses demonstrated that CREPT deletion impaired the stem potential of revSCs and inhibited their differentiation into enterocytes and goblet cells. Lineage tracing experiments confirmed the reduced regenerative capacity of CREPT-deficient revSCs in vivo. Together, our findings identified CREPT as an important regulator of revSC differentiation during intestinal regeneration.</p>","PeriodicalId":49095,"journal":{"name":"Cell and Bioscience","volume":"15 1","pages":"98"},"PeriodicalIF":6.1,"publicationDate":"2025-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12232850/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144585463","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}