Cell Death & Disease最新文献

{"title":"Correction to: The IL-6-STAT3 axis mediates a reciprocal crosstalk between cancer-derived mesenchymal stem cells and neutrophils to synergistically prompt gastric cancer progression.","authors":"Q Zhu, X Zhang, L Zhang, W Li, H Wu, X Yuan, F Mao, M Wang, W Zhu, H Qian, W Xu","doi":"10.1038/s41419-024-07100-y","DOIUrl":"10.1038/s41419-024-07100-y","url":null,"abstract":"","PeriodicalId":9734,"journal":{"name":"Cell Death & Disease","volume":null,"pages":null},"PeriodicalIF":8.1,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11445406/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142364559","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"NOD2 reduces the chemoresistance of melanoma by inhibiting the TYMS/PLK1 signaling axis.","authors":"Fang Yun, Na Wu, Xiaojia Yi, Xuedan Zhang, Yu Feng, Qinxuan Ni, Yanlong Gai, Enjiang Li, Zhe Yang, Qiao Zhang, Buqing Sai, Yingmin Kuang, Yuechun Zhu","doi":"10.1038/s41419-024-07104-8","DOIUrl":"10.1038/s41419-024-07104-8","url":null,"abstract":"<p><p>Nucleotide-binding oligomerization domain 2 (NOD2) is an immune sensor crucial for eliciting the innate immune responses. Nevertheless, discrepancies exist regarding the effect of NOD2 on different types of cancer. This study aimed to investigate these function of NOD2 in melanoma and its underlying mechanisms. We have validated the tumor suppressor effect of NOD2 in melanoma. NOD2 inhibited the proliferation of melanoma cells, hindering their migration and invasion while promoting the onset of apoptosis. Our study showed that NOD2 expression is closely related to pyrimidine and folate metabolism. NOD2 inhibits thymidylate synthase (TYMS) expression by promoting K48-type ubiquitination modification of TYMS, thereby decreasing the resistance of melanoma cells to 5-fluorouracil (5-FU) and capecitabine (CAP). TYMS was identified to form a complex with Polo-like Kinase 1 (PLK1) and activate the PLK1 signaling pathway. Furthermore, we revealed that the combination of the PLK1 inhibitor volasertib (BI6727) with 5-FU or CAP had a synergistic effect repressing the proliferation, migration, and autophagy of melanoma cells. Overall, our research highlights the protective role of NOD2 in melanoma and suggests that targeting NOD2 and the TYMS/PLK1 signaling axis is a high-profile therapy that could be a prospect for melanoma treatment.</p>","PeriodicalId":9734,"journal":{"name":"Cell Death & Disease","volume":null,"pages":null},"PeriodicalIF":8.1,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11445241/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142361197","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Serum apolipoprotein H determines ferroptosis resistance by modulating cellular lipid composition.","authors":"Xiang He, Jiahui Zhang, Masha Huang, Jie Wang, Simin Yang, Xiang Yu, Yingjie Xu, Wen Yang","doi":"10.1038/s41419-024-07099-2","DOIUrl":"10.1038/s41419-024-07099-2","url":null,"abstract":"<p><p>Ferroptosis is a regulated cell death process dependent on iron, triggered by the accumulation of lipid peroxidation. The environmental context significantly impacts cellular sensitivities to ferroptosis. Serum, constituting the extracellular fluid composition in vivo, provides crucial environmental biomolecules. In this study, we investigated the influence of sera on ferroptosis induction, pinpointing the serum protein apolipoprotein H (APOH) as a pivotal inhibitor of ferroptosis. Moreover, we elucidated that APOH suppresses ferroptosis by activating the phosphoinositide 3-kinase (PI3K)-AKT-sterol regulatory element-binding proteins (SREBPs) pathway, thereby elevating stearoyl-CoA desaturase (SCD) levels and augmenting cellular monounsaturated fatty acid-containing phospholipids (MUFA-PLs). Furthermore, ApoHinfer, the peptide derivative of the active region of APOH, mimics its ferroptosis inhibitory activity. Our findings underscore the critical role of serum protein APOH in the inhibition of ferroptosis and indicates potential therapeutic applications in treating cancer and diseases associated with ferroptosis.</p>","PeriodicalId":9734,"journal":{"name":"Cell Death & Disease","volume":null,"pages":null},"PeriodicalIF":8.1,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11445452/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142361200","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Novel FABP4⁺C1q⁺ macrophages enhance antitumor immunity and associated with response to neoadjuvant pembrolizumab and chemotherapy in NSCLC via AMPK/JAK/STAT axis.","authors":"Dong Zhang, Min Wang, Gen Liu, Xin Li, Wenwen Yu, Zhenzhen Hui, Xiubao Ren, Qian Sun","doi":"10.1038/s41419-024-07074-x","DOIUrl":"10.1038/s41419-024-07074-x","url":null,"abstract":"<p><p>Immune checkpoint inhibitors (ICIs) immunotherapy facilitates new approaches to achieve precision cancer treatment. A growing number of patients with non-small cell lung cancer (NSCLC) have benefited from treatment with neoadjuvant ICIs combined with chemotherapy. However, the mechanisms and associations between the therapeutic efficacy of neoadjuvant pembrolizumab and chemotherapy (NAPC) and macrophage subsets are still unclear. We performed single-cell RNA sequencing (scRNA-seq) and identified a novel FABP4⁺C1q⁺ macrophage subtype, which exhibited stronger proinflammatory cytokine production and phagocytic ability. This subtype was found to be more abundant in tumor tissues and lymph nodes of major pathological response (MPR) patients compared to non-MPR patients, and was associated with a good efficacy of NAPC. Multiplex fluorescent immunohistochemical (mIHC) staining was subsequently used to verify our findings. Further mechanistic studies indicated that FABP4 and C1q regulate the expression of proinflammatory cytokines synergistically. In addition, FABP4 and C1q promote fatty acid synthesis, enhance anti-apoptosis ability and phagocytic ability of macrophage via the interaction of AMPK/JAK/STAT axis. This study provides novel insights into the underlying mechanisms and predictive biomarkers of NAPC. Our findings contribute to improving the prognosis of patients with NSCLC by potentially guiding more precise patient selection and treatment strategies. NOVELTY & IMPACT STATEMENTS: We identified a group of macrophages (FABP4⁺C1q⁺ macrophages) related to the therapeutic efficacy of neoadjuvant chemoimmunotherapy. FABP4⁺C1q⁺ macrophages highly expressed proinflammatory cytokines-related genes and had a strong cytokine production and phagocytic ability. We believe that our study provides a novel insight into the synergistic mechanism of neoadjuvant ICI combined with chemotherapy and may lead to improved clinical outcomes in patients with NSCLC in the future.</p>","PeriodicalId":9734,"journal":{"name":"Cell Death & Disease","volume":null,"pages":null},"PeriodicalIF":8.1,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11445384/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142361198","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"GPR56 facilitates hepatocellular carcinoma metastasis by promoting the TGF-β signaling pathway.","authors":"Yiming Luo, Junli Lu, Zhen Lei, Dean Rao, Tiantian Wang, Chenan Fu, He Zhu, Zhiwei Zhang, Zhibin Liao, Huifang Liang, Wenjie Huang","doi":"10.1038/s41419-024-07095-6","DOIUrl":"10.1038/s41419-024-07095-6","url":null,"abstract":"<p><p>The metastasis of hepatocellular carcinoma (HCC) poses a significant threat to the survival of patients. G protein-coupled receptor 56 (GPR56) has garnered extensive attention within malignant tumor research and plays a crucial role in cellular surface signal transmission. Nonetheless, its precise function in HCC remains ambiguous. Our investigation reveals a notable rise in GPR56 expression levels in human HCC cases, with heightened GPR56 levels correlating with unfavorable prognoses. GPR56 regulates TGF-β pathway by interacting with TGFBR1, thereby promoting HCC metastasis. At the same time, GPR56 is subject to regulation by the canonical cascade of TGF-β signaling, thereby establishing a positive feedback loop. Furthermore, the combination application of TGFBR1 inhibitor galunisertib (GAL) and GPR56 inhibitor Dihydromunduletone (DHM), significantly inhibits HCC metastasis. Interventions towards this signaling pathway could offer a promising therapeutic approach to effectively impede the metastasis of GPR56-mediated HCC.</p>","PeriodicalId":9734,"journal":{"name":"Cell Death & Disease","volume":null,"pages":null},"PeriodicalIF":8.1,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11445230/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142361194","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"CD2AP promotes the progression of glioblastoma multiforme via TRIM5-mediated NF-kB signaling.","authors":"Liang Zhang, Jiawei He, Wentao Zhao, Yuhang Zhou, Jin Li, Shaobo Li, Wenpeng Zhao, Lingliang Zhang, Ziqian Tang, Guowei Tan, Sifang Chen, Bingchang Zhang, Yun-Wu Zhang, Zhanxiang Wang","doi":"10.1038/s41419-024-07094-7","DOIUrl":"10.1038/s41419-024-07094-7","url":null,"abstract":"<p><p>CD2-associated protein (CD2AP) is a scaffolding/adaptive protein that regulates intercellular adhesion and multiple signaling pathways. Although emerging evidence suggests that CD2AP is associated with several malignant tumors, there is no study investigating the expression and biological significance of CD2AP in glioblastoma multiforme (GBM). Here by studying public datasets, we found that CD2AP expression was significantly elevated in GBM and that glioma patients with increased CD2AP expression had a worse prognosis. We also confirmed the increase of CD2AP expression in clinical GBM samples and GBM cell lines. CD2AP overexpression in GBM cells promoted their proliferation, colony formation, migration, and invasion in vitro and their tumorigenesis in vivo, and reduced cell apoptosis both at basal levels and in response to temozolomide. While CD2AP knockdown had the opposite effects. Mechanistically, we revealed that CD2AP interacted with TRIM5, an NF-κB modulator. CD2AP overexpression and knockdown increased and decreased TRIM5 levels as well as the NF-κB activity, respectively. Moreover, downregulation of TRIM5 reversed elevated NF-κB activity in GBM cells with CD2AP overexpression; and inhibition of the NF-κB activity attenuated malignant features of GBM cells with CD2AP overexpression. Our findings demonstrate that CD2AP promotes GBM progression through activating TRIM5-mediated NF-κB signaling and that downregulation of CD2AP can attenuate GBM malignancy, suggesting that CD2AP may become a biomarker and the CD2AP-TRIM5-NF-κB axis may become a therapeutic target for GBM.</p>","PeriodicalId":9734,"journal":{"name":"Cell Death & Disease","volume":null,"pages":null},"PeriodicalIF":8.1,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11445578/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142361192","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Deciphering the impact of PROM1 alternative splicing on human photoreceptor development and maturation.","authors":"Marina Moya-Molina, Birthe Dorgau, Emily Flood, Stef J F Letteboer, Esben Lorentzen, Jonathan Coxhead, Graham Smith, Ronald Roepman, Sushma Nagaraja Grellscheid, Lyle Armstrong, Majlinda Lako","doi":"10.1038/s41419-024-07105-7","DOIUrl":"10.1038/s41419-024-07105-7","url":null,"abstract":"<p><p>Alternative splicing (AS) is a crucial mechanism contributing to proteomic diversity, which is highly regulated in tissue- and development-specific patterns. Retinal tissue exhibits one of the highest levels of AS. In particular, photoreceptors have a distinctive AS pattern involving the inclusion of microexons not found in other cell types. PROM1 whose encoded protein Prominin-1 is located in photoreceptor outer segments (OSs), undergoes exon 4 inclusion from the 12^th post-conception week of human development through adulthood. Exon 4 skipping in PROM1 is associated with late-onset mild maculopathy, however its role in photoreceptor maturation and function is unknown. In this study retinal organoids, a valuable model system, were employed in combination with phosphorodiamidate morpholino oligos (PMOs) to assess the role of exon 4 AS in the development of human retina. Retinal organoids were treated with the PMOs for four weeks after which RT-PCR, western blotting and immunofluorescence analysis were performed to assess exon 4 exclusion and its impact on photoreceptors. The transcriptome of treated ROs was studied by bulk RNA-Seq. Our data demonstrate that 55% skipping of PROM1 exon 4 resulted in decreased Prominin-1 expression by 40%, abnormal accumulation of cones in the basal side of the retinal organoids as well as detectable cone photoreceptor cilium defects. Transcriptomic and western blot analyses revealed decreased expression of cone, inner segment and connecting cilium basal body markers, increased expression of genes associated with stress response and the ubiquitin-proteasome system, and downregulation of autophagy. Importantly, the use of retinal organoids provides a valuable platform to study AS and unravel disease mechanisms in a more physiologically relevant context, opening avenues for further research and potential therapeutic interventions. Together our data indicate that cones may be more sensitive to PROM1 exon 4 skipping and/or reduced Prominin-1 expression, corroborating the pathogenesis of late-onset mild maculopathy.</p>","PeriodicalId":9734,"journal":{"name":"Cell Death & Disease","volume":null,"pages":null},"PeriodicalIF":8.1,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11445533/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142361193","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cholesterol inhibition enhances antitumor response of gilteritinib in lung cancer cells.","authors":"Chao-Yue Sun, Di Cao, Yue-Ning Wang, Nuo-Qing Weng, Qian-Nan Ren, Shuo-Cheng Wang, Mei-Yin Zhang, Shi-Juan Mai, Hui-Yun Wang","doi":"10.1038/s41419-024-07082-x","DOIUrl":"10.1038/s41419-024-07082-x","url":null,"abstract":"<p><p>Repositioning approved antitumor drugs for different cancers is a cost-effective approach. Gilteritinib was FDA-approved for the treatment of FLT3-mutated acute myeloid leukemia in 2018. However, the therapeutic effects and mechanism of Gilteritinib on other malignancies remain to be defined. In this study, we identified that gilteritinib has an inhibitory effect on lung cancer cells (LCCs) without FLT3 mutation in vitro and in vivo. Unexpectedly, we found that gilteritinib induces cholesterol accumulation in LCCs via upregulating cholesterol biosynthetic genes and inhibiting cholesterol efflux. This gilteritinib-induced cholesterol accumulation not only attenuates the antitumor effect of gilteritinib but also induces gilteritinib-resistance in LCCs. However, when cholesterol synthesis was prevented by squalene epoxidase (SQLE) inhibitor NB-598, both LCCs and gilteritinib-resistant LCCs became sensitive to gilteritinib. More importantly, the natural cholesterol inhibitor 25-hydroxycholesterol (25HC) can suppress cholesterol biosynthesis and increase cholesterol efflux in LCCs. Consequently, 25HC treatment significantly increases the cytotoxicity of gilteritinib on LCCs, which can be rescued by the addition of exogenous cholesterol. In a xenograft model, the combination of gilteritinib and 25HC showed significantly better efficacy than either monotherapy in suppressing lung cancer growth, without obvious general toxicity. Thus, our findings identify an increase in cholesterol induced by gilteritinib as a mechanism for LCC survival, and highlight the potential of combining gilteritinib with cholesterol-lowering drugs to treat lung cancer.</p>","PeriodicalId":9734,"journal":{"name":"Cell Death & Disease","volume":null,"pages":null},"PeriodicalIF":8.1,"publicationDate":"2024-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11443066/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142342465","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"LncRNA PVT1 induces mitochondrial dysfunction of podocytes via TRIM56 in diabetic kidney disease.","authors":"Zhimei Lv, Ziyang Wang, Jinxiu Hu, Hong Su, Bing Liu, Yating Lang, Qun Yu, Yue Liu, Xiaoting Fan, Meilin Yang, Ning Shen, Dongdong Zhang, Xia Zhang, Rong Wang","doi":"10.1038/s41419-024-07107-5","DOIUrl":"10.1038/s41419-024-07107-5","url":null,"abstract":"<p><p>Mitochondrial dysfunction is a significant contributor to podocyte injury in diabetic kidney disease (DKD). While previous studies have shown that PVT1 might play a vital role in DKD, the precise molecular mechanisms are largely unknown. By analyzing the plasma and kidney tissues of DKD patients, we observed a significant upregulation of PVT1 expression, which exhibited a positive correlation with albumin/creatinine ratios and serum creatinine levels. Then, we generated mice with podocyte-specific deletion of PVT1 (Nphs2-Cre/Pvt1^flox/flox) and confirmed that the deletion of PVT1 suppressed podocyte mitochondrial dysfunction and inflammation in addition to ameliorating diabetes-induced podocyte injury, glomerulopathy, and proteinuria. Subsequently, we cultured podocytes in vitro and observed that PVT1 expression was upregulated under hyperglycemic conditions. Mechanistically, we demonstrated that PVT1 was involved in mitochondrial dysfunction by interacting with TRIM56 post-transcriptionally to modulate the ubiquitination of AMPKα, leading to aberrant mitochondrial biogenesis and fission. Additionally, the release of mtDNA and mtROS from damaged mitochondria triggered inflammation in podocytes. Subsequently, we verified the important role of TRIM56 in vivo by constructing Nphs2-Cre/Trim56^flox/flox mice, consistently with the results of Nphs2-Cre/Pvt1^flox/flox mice. Together, our results revealed that upregulation of PVT1 could promote mitochondrial dysfunction and inflammation of podocyte by modulating TRIM56, highlighting a potential novel therapeutic target for DKD.</p>","PeriodicalId":9734,"journal":{"name":"Cell Death & Disease","volume":null,"pages":null},"PeriodicalIF":8.1,"publicationDate":"2024-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11442824/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142342372","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"SALL2 regulates neural differentiation of mouse embryonic stem cells through Tuba1a.","authors":"Hui Xiong, Bowen Lin, Junyang Liu, Renhong Lu, Zheyi Lin, Chengwen Hang, Wenjun Liu, Lei Zhang, Jie Ding, Huixin Guo, Mingshuai Zhang, Siyu Wang, Zheng Gong, Duanyang Xie, Yi Liu, Dan Shi, Dandan Liang, Zhen Liu, Yi-Han Chen, Jian Yang","doi":"10.1038/s41419-024-07088-5","DOIUrl":"10.1038/s41419-024-07088-5","url":null,"abstract":"<p><p>The spalt (Sal) gene family has four members (Sall1-4) in vertebrates, all of which play pivotal roles in various biological processes and diseases. However, the expression and function of SALL2 in development are still less clear. Here, we first charted SALL2 protein expression pattern during mouse embryo development by immunofluorescence, which revealed its dominant expression in the developing nervous system. With the establishment of Sall2 deficient mouse embryonic stem cells (ESCs), the in vitro neural differentiation system was leveraged to interrogate the function of SALL2, which showed impaired neural differentiation of Sall2 knockout (KO) ESCs. Furthermore, neural stem cells (NSCs) could not be derived from Sall2 KO ESCs and the generation of neural tube organoids (NTOs) was greatly inhibited in the absence of SALL2. Meanwhile, transgenic expression of E1 isoform of SALL2 restored the defects of neural differentiation in Sall2 KO ESCs. By chromatin immunoprecipitation sequencing (ChIP-seq), Tuba1a was identified as downstream target of SALL2, whose function in neural differentiation was confirmed by rescuing neural phenotypes of Sall2 KO ESCs when overexpressed. In sum, by elucidating SALL2 expression dynamics during early mouse development and mechanistically characterizing its indispensable role in neural differentiation, this study offers insights into SALL2's function in human nervous system development, associated pathologies stemming from its mutations and relevant therapeutic strategy.</p>","PeriodicalId":9734,"journal":{"name":"Cell Death & Disease","volume":null,"pages":null},"PeriodicalIF":8.1,"publicationDate":"2024-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11442768/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142342375","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}