Theranostics最新文献

{"title":"Photoreceptor-targeted extracellular vesicles-mediated delivery of Cul7 siRNA for retinal degeneration therapy","authors":"Dong Guo, Yuntong Sun, Junqi Wu, Linchao Ding, Yiwen Jiang, Yadong Xue, Yongjun Ma, Fengtian Sun","doi":"10.7150/thno.99484","DOIUrl":"https://doi.org/10.7150/thno.99484","url":null,"abstract":"<b>Rationale:</b> Photoreceptor loss is a primary pathological feature of retinal degeneration (RD) with limited treatment strategies. RNA interference (RNAi) has emerged as a promising method of gene therapy in regenerative medicine. However, the transfer of RNAi therapeutics to photoreceptors and the deficiency of effective therapeutic targets are still major challenges in the treatment of RD./n<b>Methods:</b> In this study, photoreceptor-derived extracellular vesicles (PEVs) conjugated with photoreceptor-binding peptide MH42 (PEVs^MH42) were prepared using the anchoring peptide CP05. Transcriptome sequencing was applied to investigate the potential therapeutic target of RD. We then engineered PEVs^MH42 with specific small-interfering RNAs (siRNAs) through electroporation and evaluated their therapeutic efficacy in N-methyl-N-nitrosourea (MNU)-induced RD mice and Pde6β^rd1/rd1 mutant mice./n<b>Results:</b> PEVs^MH42 were selectively accumulated in photoreceptors after intravitreal injection. Cullin-7 (Cul7) was identified as a novel therapeutic target of RD. Taking advantage of the established PEVs^MH42, siRNAs targeting Cul7 (siCul7) were efficiently delivered to photoreceptors and consequently blocked the expression of Cul7. Moreover, suppression of Cul7 effectively protected photoreceptors to alleviate RD both in MNU-induced mouse model and Pde6β^rd1/rd1 mutant mouse model. Mechanistically, PEVs^MH42 loaded with siCul7 (PEVs^MH42-siCul7)-induced Cul7 downregulation was responsible for preventing Cul7-mediated glutathione peroxidase 4 (Gpx4) ubiquitination and degradation, resulting in the inhibition of photoreceptor ferroptosis./n<b>Conclusions:</b> In summary, PEVs^MH42-siCul7 attenuate photoreceptor ferroptosis to treat RD by inhibiting Cul7-induced ubiquitination of Gpx4. Our study develops a PEVs-based platform for photoreceptor-targeted delivery and highlights the potential of PEVs^MH42-siCul7 as effective therapeutics for RD.","PeriodicalId":22932,"journal":{"name":"Theranostics","volume":null,"pages":null},"PeriodicalIF":12.4,"publicationDate":"2024-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142187014","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Single cell RNA-sequencing delineates CD8⁺ tissue resident memory T cells maintaining rejection in liver transplantation.","authors":"Xinqiang Li, Shipeng Li, Yan Wang, Xin Zhou, Feng Wang, Imran Muhammad, Yurong Luo, Yandong Sun, Dan Liu, Bin Wu, Dahong Teng, Jinshan Wang, Kai Zhao, Qi Ling, Jinzhen Cai","doi":"10.7150/thno.96928","DOIUrl":"10.7150/thno.96928","url":null,"abstract":"<p><p><b>Rationale:</b> Understanding the immune mechanisms associated with liver transplantation (LT), particularly the involvement of tissue-resident memory T cells (TRMs), represents a significant challenge. <b>Methods:</b> This study employs a multi-omics approach to analyse liver transplant samples from both human (n = 17) and mouse (n = 16), utilizing single-cell RNA sequencing, bulk RNA sequencing, and immunological techniques. <b>Results:</b> Our findings reveal a comprehensive T cell-centric landscape in LT across human and mouse species, involving 235,116 cells. Notably, we found a substantial increase in CD8⁺ TRMs within rejected grafts compared to stable ones. The elevated presence of CD8⁺ TRMs is characterised by a distinct expression profile, featuring upregulation of tissue-residency markers (CD69, CXCR6, CD49A and CD103^+/-,), immune checkpoints (PD1, CTLA4, and TIGIT), cytotoxic markers (GZMB and IFNG) and proliferative markers (PCNA and TOP2A) during rejection. Furthermore, there is a high expression of transcription factors such as EOMES and RUNX3. Functional assays and analyses of cellular communication underscore the active role of CD8⁺ TRMs in interacting with other tissue-resident cells, particularly Kupffer cells, especially during rejection episodes. <b>Conclusions:</b> These insights into the distinctive activation and interaction patterns of CD8⁺ TRMs suggest their potential utility as biomarkers for graft rejection, paving the way for novel therapeutic strategies aimed at enhancing graft tolerance and improving overall transplant outcomes.</p>","PeriodicalId":22932,"journal":{"name":"Theranostics","volume":null,"pages":null},"PeriodicalIF":12.4,"publicationDate":"2024-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11373625/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142141166","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Engaging natural regulatory myeloid cells to restrict T-cell hyperactivation-induced liver inflammation via extracellular vesicle-mediated purine metabolism regulation.","authors":"Fan Yang, Ruoting Men, Linling Lv, Leyu Zhou, Qiaoyu Deng, Xianglin Wang, Jingping Liu, Li Yang","doi":"10.7150/thno.97427","DOIUrl":"10.7150/thno.97427","url":null,"abstract":"<p><p><b>Rationale:</b> Dysregulated T-cell immune response-mediated inflammation plays critical roles in the pathology of diverse liver diseases, but the underlying mechanism of liver immune homeostasis control and the specific therapies for limiting T-cell overactivation remain unclear. <b>Methods:</b> The metabolic changes in concanavalin A (ConA) mice and autoimmune hepatitis (AIH) patients and their associations with liver injury were analyzed. The expression of purine catabolism nucleases (e.g., CD39 and CD73) on liver cells and immune cells was assessed. The effects of MCregs and their extracellular vesicles (EVs) on CD4⁺ T-cell overactivation and the underlying mechanism were also explored. <b>Results:</b> Our findings revealed significant alterations in purine metabolism in ConA mice and AIH patients, which correlated with liver injury severity and therapeutic response. CD39 and CD73 were markedly upregulated on CD11b⁺Gr-1⁺ MCs under liver injury conditions. The naturally expanded CD39⁺CD73⁺Gr-1^highCD11b⁺ MCreg subset during early liver injury effectively suppressed CD4⁺ T-cell hyperactivation and liver injury both in vitro and in vivo. Mechanistically, MCregs released CD73^high EVs, which converted extracellular AMP to immunosuppressive metabolites (e.g., adenosine and inosine), activating the cAMP pathway and inhibiting glycolysis and cytokine secretion in activated CD4⁺ T cells. <b>Conclusions:</b> This study provides insights into the mechanism controlling immune homeostasis during the early liver injury phase and highlights that MCreg or MCreg-EV therapy may be a specific strategy for preventing diverse liver diseases induced by T-cell overactivation.</p>","PeriodicalId":22932,"journal":{"name":"Theranostics","volume":null,"pages":null},"PeriodicalIF":12.4,"publicationDate":"2024-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11373623/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142141150","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Oncofetal TRIM71 drives liver cancer carcinogenesis through remodeling CEBPA-mediated serine/glycine metabolism","authors":"Ying Su, Ziteng Li, Qin Li, Xinyi Guo, Hena Zhang, Yan Li, Zhiqiang Meng, Shenglin Huang, Zhixiang Hu","doi":"10.7150/thno.99633","DOIUrl":"https://doi.org/10.7150/thno.99633","url":null,"abstract":"<b>Rationale:</b> Tumor cells remodel transcriptome to construct an ecosystem with stemness features, which maintains tumor growth and highly malignant characteristics. However, the core regulatory factors involved in this process still need to be further discovered./n<b>Methods:</b> Single cell RNA-sequncing (scRNA-seq) and bulk RNA-sequencing profiles derived from fetal liver, normal liver, liver tumors, and their adjacent samples were collected to analyze the ecosystem of liver cancer. Mouse models were established to identify molecular functions of oncofetal-related oncogenes using hydrodynamic tail vein injection./n<b>Results:</b> We found that liver cancer rebuilt oncofetal ecosystem to maintain malignant features. Interestingly, we identified a group of RNA-binding proteins (RBPs) that were highly overexpressed with oncofetal features. Among them, TRIM71 was specifically expressed in liver cancers and was associated with poor outcomes. TRIM71 drove the carcinogenesis of hepatocellular carcinoma (HCC), and knockdown of TRIM71 significantly abolished liver cancer cell proliferation. Mechanistically, TRIM71 formed a protein complex with IGF2BP1, bound to and stabilized the mRNA of CEBPA in an m6A-dependent manner, enhance the serine/glycine metabolic pathway, and ultimately promoted liver cancer progression. Furthermore, we identified that all-trans-retinoic acid (ATRA) combined with e1A binding protein p300 (EP300) inhibitor A-485 repressed TRIM71, attenuated glycine/serine metabolism, and inhibited liver cancer cell proliferation with high TRIM71 levels./n<b>Conclusions:</b> We demonstrated the oncofetal status in liver cancer and highlighted the crucial role of TRIM71 and provided potential therapeutic strategies and liver cancer-specific biomarker for liver cancer patients.","PeriodicalId":22932,"journal":{"name":"Theranostics","volume":null,"pages":null},"PeriodicalIF":12.4,"publicationDate":"2024-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142186989","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Metal-organic cage as a theranostic nanoplatform for magnetic resonance imaging guided chemodynamic therapy.","authors":"Peilin Yin, Demei Sun, Yucen Deng, Xinyuan Zhu, Youfu Wang, Jinghui Yang, Xuesong Feng","doi":"10.7150/thno.97264","DOIUrl":"10.7150/thno.97264","url":null,"abstract":"<p><p><b>Rationale:</b> Theranostic nanoplatforms exert a vital role in facilitating concurrent real-time diagnosis and on-demand treatment of diseases, thereby making contributions to the improvement of therapeutic efficacy. Nevertheless, the structural intricacy and the absence of well-defined integration of dual functionality persist as challenges in the development of theranostic nanoplatforms. <b>Methods:</b> We develop an atomically precise theranostic nanoplatform based on metal-organic cage (MOC) to provide magnetic resonance imaging (MRI) guided chemodynamic therapy (CDT) for cancer therapy and assess the theranostic performance both <i>in vitro</i> and <i>in vivo</i>. Through UV-vis spectroscopy, electron paramagnetic resonance (EPR), confocal microscopy, flow cytometry, immunofluorescence staining, and western blotting, the ability of MOC-Mn to generate •OH and the subsequent inhibition of HeLa cells was confirmed. <b>Results:</b> The MOC-Mn composed of manganese and calixarene was successfully synthesized and comprehensively characterized. The catalytic activity of manganese within MOC-Mn facilitated the efficient generation of hydroxyl radicals (•OH) through a Fenton-like reaction, leveraging the high concentrations of hydrogen peroxide in the tumor microenvironment (TME). Additionally, its capacity to prolong the T1 relaxation time and augment the MR signal was observed. The theranostic efficacy was verified <i>via</i> rigorous <i>in vitro</i> and <i>in vivo</i> experiments, indicating that MOC-Mn offered clearer visualization of tumor particulars and substantial suppression of tumor growth. <b>Conclusion:</b> This study showcases a precise MRI-guided CDT theranostic nanoplatform for cancer therapy, thereby promoting the advancement of precise nanomedicine and structure-function research.</p>","PeriodicalId":22932,"journal":{"name":"Theranostics","volume":null,"pages":null},"PeriodicalIF":12.4,"publicationDate":"2024-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11373615/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142141163","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Bacteria-based cascade in situ near-infrared nano-optogenetically induced photothermal tumor therapy","authors":"Xiuwen Hu, Jiawen Chen, Yuzhi Qiu, Sihan Chen, Yidi Liu, Xi Yu, Yunting Liu, Xiangliang Yang, Yan Zhang, Yanhong Zhu","doi":"10.7150/thno.98097","DOIUrl":"https://doi.org/10.7150/thno.98097","url":null,"abstract":"<b>Rationale:</b> Optogenetically engineered facultative anaerobic bacteria exhibit a favorable tendency to colonize at solid tumor sites and spatiotemporally-programmable therapeutics release abilities, attracting extensive attention in precision tumor therapy. However, their therapeutic efficacy is moderate. Conventional photothermal agents with high tumor ablation capabilities exhibit low tumor targeting efficiency, resulting in significant off-target side effects. The combination of optogenetics and photothermal therapy may offer both tumor-targeting and excellent tumor-elimination capabilities, which unfortunately has rarely been investigated. Herein, we construct a bacteria-based cascade near-infrared optogentical-photothermal system (EcN_αHL-UCNPs) for enhanced tumor therapy./n<b>Methods:</b> EcN_αHL-UCNPs consists of an optogenetically engineered Escherichia coli Nissle 1917 (EcN) conjugated with lanthanide-doped upconversion nanoparticles (UCNPs), which are capable of locally secreting α-hemolysin (αHL), a pore-forming protein, in responsive to NIR irradiation. Anti-tumor effects of EcN_αHL-UCNPs were determined in both H22 and 4T1 tumors./n<b>Results:</b> The αHL not only eliminates tumor cells, but more importantly disrupts endothelium to form thrombosis as an <i>in situ</i> photothermal agent in tumors. The <i>in situ</i> formed thrombosis significantly potentiates the photothermic ablation of H22 tumors upon subsequent NIR light irradiation. Besides, αHL secreted by EcN_αHL-UCNPs under NIR light irradiation not only inhibits 4T1 tumor growth, but also suppresses metastasis of 4T1 tumor via inducing the immune response./n<b>Conclusion:</b> Our studies highlight bacteria-based cascade optogenetical-photothermal system for precise and effective tumor therapy.","PeriodicalId":22932,"journal":{"name":"Theranostics","volume":null,"pages":null},"PeriodicalIF":12.4,"publicationDate":"2024-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142186988","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Molecular imaging nanoprobes and their applications in atherosclerosis diagnosis.","authors":"Huari Kou, Hu Yang","doi":"10.7150/thno.96037","DOIUrl":"10.7150/thno.96037","url":null,"abstract":"<p><p>Molecular imaging has undergone significant development in recent years for its excellent ability to image and quantify biologic processes at cellular and molecular levels. Its application is of significance in cardiovascular diseases, particularly in diagnosing them at early stages. Atherosclerosis is a complex, chronic, and progressive disease that can lead to serious consequences such as heart strokes or infarctions. Attempts have been made to detect atherosclerosis with molecular imaging modalities. Not only do imaging modalities develop rapidly, but research of relevant nanomaterials as imaging probes has also been increasingly studied in recent years. This review focuses on the latest developments in the design and synthesis of probes that can be utilized in computed tomography, positron emission tomography, magnetic resonance imaging, ultrasound imaging, photoacoustic imaging and combined modalities. The challenges and future developments of nanomaterials for molecular imaging modalities are also discussed.</p>","PeriodicalId":22932,"journal":{"name":"Theranostics","volume":null,"pages":null},"PeriodicalIF":12.4,"publicationDate":"2024-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11373619/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142141164","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The principles and promising future of sonogenetics for precision medicine.","authors":"Pengying Wu, Zhaoyou Liu, Wenxin Tao, Yubo Lai, Guodong Yang, Lijun Yuan","doi":"10.7150/thno.98476","DOIUrl":"10.7150/thno.98476","url":null,"abstract":"<p><p>Sonogenetics is an emerging medical technology that uses acoustic waves to control cells through sonosensitive mediators (SSMs) that are genetically encoded, thus remotely and non-invasively modulating specific molecular events and/or biomolecular functions. Sonogenetics has opened new opportunities for targeted spatiotemporal manipulation in the field of gene and cell-based therapies due to its inherent advantages, such as its noninvasive nature, high level of safety, and deep tissue penetration. Sonogenetics holds impressive potential in a wide range of applications, from tumor immunotherapy and mitigation of Parkinsonian symptoms to the modulation of neural reward pathway, and restoration of vision. This review provides a detailed overview of the mechanisms and classifications of established sonogenetics systems and summarizes their applications in disease treatment and management. The review concludes by highlighting the challenges that hinder the further progress of sonogenetics, paving the way for future advances.</p>","PeriodicalId":22932,"journal":{"name":"Theranostics","volume":null,"pages":null},"PeriodicalIF":12.4,"publicationDate":"2024-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11373633/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142141181","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Single-cell RNA sequencing highlights the immunosuppression of IDO1⁺ macrophages in the malignant transformation of oral leukoplakia.","authors":"Yu Zhang, Jie Zhang, Simin Zhao, Yan Xu, Yingying Huang, Shaopeng Liu, Peng Su, Caijiao Wang, Yahui Li, Hao Li, Pishan Yang, Chengzhe Yang","doi":"10.7150/thno.99112","DOIUrl":"10.7150/thno.99112","url":null,"abstract":"<p><p><b>Rationale</b>: Immunosuppressive tumor microenvironment (iTME) plays an important role in carcinogenesis, and some macrophage subsets are associated with iTME generation. However, the sub-population characterization of macrophages in oral carcinogenesis remains largely unclear. Here, we investigated the immunosuppressive status with focus on function of a macrophage subset that expressed indoleamine 2,3 dioxygenase 1 (Macro-IDO1) in oral carcinogenesis. <b>Methods</b>: We built a single cell transcriptome atlas from 3 patients simultaneously containing oral squamous cell carcinoma (OSCC), precancerous oral leukoplakia (preca-OLK) and paracancerous tissue (PCA). Through single-cell RNA sequencing and further validation using multicolor immunofluorescence staining and the <i>in vitro</i>/<i>in vivo</i> experiments, the immunosuppressive cell profiles were built and the role of a macrophage subset that expressed indoleamine 2,3 dioxygenase 1 (Macro-IDO1) in the malignant transformation of oral leukoplakia was evaluated. <b>Results</b>: The iTME formed at preca-OLK stage, as evidenced by increased exhausted T cells, Tregs and some special subsets of macrophages and fibroblasts. Macro-IDO1 was predominantly enriched in preca-OLK and OSCC, distributed near exhausted T cells and possessed tumor associated macrophage transformation potentials. Functional analysis revealed the established immunosuppressive role of Macro-IDO1 in preca-OLK and OSCC: enriching the immunosuppression related genes; having an established level of immune checkpoint score; exerting strong immunosuppressive interaction with T cells; positively correlating with the CD8-exhausted. The immunosuppression related gene expression of macrophages also increased in preca-OLK/OSCC compared to PCA. The use of the IDO1 inhibitor reduced 4NQO induced oral carcinogenesis in mice. Mechanistically, IFN-γ-JAK-STAT pathway was associated with IDO1 upregulation in OLK and OSCC. <b>Conclusions</b>: These results highlight that Macro-IDO1-enriched in preca-OLK possesses a strong immunosuppressive role and contributes to oral carcinogenesis, providing a potential target for preventing precancerous legions from transformation into OSCC.</p>","PeriodicalId":22932,"journal":{"name":"Theranostics","volume":null,"pages":null},"PeriodicalIF":12.4,"publicationDate":"2024-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11373622/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142141179","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Transcriptome analysis reveals EBF1 ablation-induced injuries in cardiac system.","authors":"Yueheng Wu, Shaoxian Chen, Guiping Huang, Lu Zhang, Liying Zhong, Yi Feng, Pengju Wen, Juli Liu","doi":"10.7150/thno.92060","DOIUrl":"10.7150/thno.92060","url":null,"abstract":"<p><p><b>Rationale:</b> Regulatory processes of transcription factors (TFs) shape heart development and influence the adult heart's response to stress, contributing to cardiac disorders. Despite their significance, the precise mechanisms underpinning TF-mediated regulation remain elusive. Here, we identify that EBF1, as a TF, is highly expressed in human heart tissues. EBF1 is reported to be associated with human cardiovascular disease, but its roles are unclear in heart. In this study, we investigated EBF1 function in cardiac system. <b>Methods:</b> RNA-seq was utilized to profile EBF1 expression patterns. CRISPR/Cas9 was utilized to knock out EBF1 to investigate its effects. Human pluripotent stem cells (hPSCs) differentiated into cardiac lineages were used to mimic cardiac development. Cardiac function was evaluated on mouse model with Ebf1 knockout by using techniques such as echocardiography. RNA-seq was conducted to analyze transcriptional perturbations. ChIP-seq was employed to elucidate EBF1-bound genes and the underlying regulatory mechanisms. <b>Results:</b> EBF1 was expressed in some human and mouse cardiomyocyte. Knockout of EBF1 inhibited cardiac development. ChIP-seq indicated EBF1's binding on promoters of cardiogenic TFs pivotal to cardiac development, facilitating their transcriptional expression and promoting cardiac development. In mouse, Ebf1 depletion triggered transcriptional perturbations of genes, resulting in cardiac remodeling. Mechanistically, we found that EBF1 directly bound to upstream chromatin regions of cardiac hypertrophy-inducing genes, contributing to cardiac hypertrophy. <b>Conclusions:</b> We uncover the mechanisms underlying EBF1-mediated regulatory processes, shedding light on cardiac development, and the pathogenesis of cardiac remodeling. These findings emphasize EBF1's critical role in orchestrating diverse aspects of cardiac processes and provide a promising therapeutic intervention for cardiomyopathy.</p>","PeriodicalId":22932,"journal":{"name":"Theranostics","volume":null,"pages":null},"PeriodicalIF":12.4,"publicationDate":"2024-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11373621/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142141183","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}