STEM CELLS最新文献_第2页

Derivation of dental epithelial-like cells from murine embryonic stem cells for tooth regeneration. 从小鼠胚胎干细胞中衍生出用于牙齿再生的牙上皮样细胞。

IF 4 2区医学

STEM CELLS Pub Date : 2024-11-05 DOI: 10.1093/stmcls/sxae052

Hong Hu, Yifan Zhao, Ce Shan, Huancheng Fu, Jinglei Cai, Zhonghan Li

{"title":"Derivation of dental epithelial-like cells from murine embryonic stem cells for tooth regeneration.","authors":"Hong Hu, Yifan Zhao, Ce Shan, Huancheng Fu, Jinglei Cai, Zhonghan Li","doi":"10.1093/stmcls/sxae052","DOIUrl":"10.1093/stmcls/sxae052","url":null,"abstract":"Teeth are comprised of epithelial and mesenchymal cells, and regenerative teeth rely on the regeneration of both cell types. Transcription factors play a pivotal role in cell fate determination. In this study, we establish fluorescence models based on transcription factors to monitor and analyze dental epithelial cells. Using Pitx2-P2A-copGFP mice, we observe that Pitx2+ epithelial cells, when combined with E14.5 dental mesenchymal cells, are sufficient for the reconstitution of teeth. Induced-Pitx2+ cells, directly isolated from the embryoid body that employs the Pitx2-GFP embryonic stem cell line, exhibit the capacity to differentiate into ameloblasts and develop into teeth when combined with dental mesenchymal cells. The regenerated teeth exhibit a complete structure, including dental pulp, dentin, enamel, and periodontal ligaments. Subsequent exploration via RNA-seq reveals that induced-Pitx2+ cells exhibit enrichment in genes associated with FGF receptors and WNT ligands compared with induced-Pitx2- cells. Our results indicate that both primary Pitx2+ and induced Pitx2+ cells possess the capability to differentiate into enamel-secreting ameloblasts and grow into teeth when combined with dental mesenchymal cells.","PeriodicalId":231,"journal":{"name":"STEM CELLS","volume":" ","pages":"945-956"},"PeriodicalIF":4.0,"publicationDate":"2024-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142034678","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

The global evolution and impact of systems biology and artificial intelligence in stem cell research and therapeutics development: a scoping review. 系统生物学和人工智能在干细胞研究和治疗开发中的全球演变和影响：范围综述》。

IF 4 2区医学

STEM CELLS Pub Date : 2024-11-05 DOI: 10.1093/stmcls/sxae054

Thayna Silva-Sousa, Júlia Nakanishi Usuda, Nada Al-Arawe, Francisca Frias, Irene Hinterseher, Rusan Catar, Christian Luecht, Katarina Riesner, Alexander Hackel, Lena F Schimke, Haroldo Dutra Dias, Igor Salerno Filgueiras, Helder I Nakaya, Niels Olsen Saraiva Camara, Stefan Fischer, Gabriela Riemekasten, Olle Ringdén, Olaf Penack, Tobias Winkler, Georg Duda, Dennyson Leandro M Fonseca, Otávio Cabral-Marques, Guido Moll

{"title":"The global evolution and impact of systems biology and artificial intelligence in stem cell research and therapeutics development: a scoping review.","authors":"Thayna Silva-Sousa, Júlia Nakanishi Usuda, Nada Al-Arawe, Francisca Frias, Irene Hinterseher, Rusan Catar, Christian Luecht, Katarina Riesner, Alexander Hackel, Lena F Schimke, Haroldo Dutra Dias, Igor Salerno Filgueiras, Helder I Nakaya, Niels Olsen Saraiva Camara, Stefan Fischer, Gabriela Riemekasten, Olle Ringdén, Olaf Penack, Tobias Winkler, Georg Duda, Dennyson Leandro M Fonseca, Otávio Cabral-Marques, Guido Moll","doi":"10.1093/stmcls/sxae054","DOIUrl":"10.1093/stmcls/sxae054","url":null,"abstract":"Advanced bioinformatics analysis, such as systems biology (SysBio) and artificial intelligence (AI) approaches, including machine learning (ML) and deep learning (DL), is increasingly present in stem cell (SC) research. An approximate timeline on these developments and their global impact is still lacking. We conducted a scoping review on the contribution of SysBio and AI analysis to SC research and therapy development based on literature published in PubMed between 2000 and 2024. We identified an 8 to 10-fold increase in research output related to all 3 search terms between 2000 and 2021, with a 10-fold increase in AI-related production since 2010. Use of SysBio and AI still predominates in preclinical basic research with increasing use in clinically oriented translational medicine since 2010. SysBio- and AI-related research was found all over the globe, with SysBio output led by the (US, n = 1487), (UK, n = 1094), Germany (n = 355), The Netherlands (n = 339), Russia (n = 215), and France (n = 149), while for AI-related research the US (n = 853) and UK (n = 258) take a strong lead, followed by Switzerland (n = 69), The Netherlands (n = 37), and Germany (n = 19). The US and UK are most active in SCs publications related to AI/ML and AI/DL. The prominent use of SysBio in ESC research was recently overtaken by prominent use of AI in iPSC and MSC research. This study reveals the global evolution and growing intersection among AI, SysBio, and SC research over the past 2 decades, with substantial growth in all 3 fields and exponential increases in AI-related research in the past decade.","PeriodicalId":231,"journal":{"name":"STEM CELLS","volume":" ","pages":"929-944"},"PeriodicalIF":4.0,"publicationDate":"2024-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142124308","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

A de novo Missense Mutation in PPP2R5D Alters Dopamine Pathways and Morphology of iPSC-derived Midbrain Neurons. PPP2R5D中的一个新发缺义突变改变了多巴胺通路和iPSC衍生中脑神经元的形态。

IF 4 2区医学

STEM CELLS Pub Date : 2024-10-26 DOI: 10.1093/stmcls/sxae068

Jasmine L Carter, Julian A N M Halmai, Jennifer J Waldo, Paula A Vij, Maribel Anguiano, Isaac J Villegas, Yu Xin Du, Jan Nolta, Kyle D Fink

{"title":"A de novo Missense Mutation in PPP2R5D Alters Dopamine Pathways and Morphology of iPSC-derived Midbrain Neurons.","authors":"Jasmine L Carter, Julian A N M Halmai, Jennifer J Waldo, Paula A Vij, Maribel Anguiano, Isaac J Villegas, Yu Xin Du, Jan Nolta, Kyle D Fink","doi":"10.1093/stmcls/sxae068","DOIUrl":"https://doi.org/10.1093/stmcls/sxae068","url":null,"abstract":"Induced pluripotent stem cell (iPSC) models of neurodevelopmental disorders (NDDs) have promoted an understanding of commonalities and differences within or across patient populations by revealing the underlying molecular and cellular mechanisms contributing to disease pathology. Here, we focus on developing a human model for PPP2R5D-related NDD, called Jordan syndrome, which has been linked to Early-Onset Parkinson's Disease (EOPD). Here we sought to understand the underlying molecular and cellular phenotypes across multiple cell states and neuronal subtypes in order to gain insight into Jordan syndrome pathology. Our work revealed that iPSC-derived midbrain neurons from Jordan syndrome patients display significant differences in dopamine-associated pathways and neuronal architecture. We then evaluated a CRISPR-based approach for editing heterozygous dominant G-to-A mutations at the transcript level in patient-derived neural stem cells. Our findings show site-directed RNA editing is influenced by sgRNA length and cell type. These studies support the potential for a CRISPR RNA editor system to selectively edit mutant transcripts harboring G-to-A mutations in neural stem cells while providing an alternative editing technology for those suffering from NDDs.","PeriodicalId":231,"journal":{"name":"STEM CELLS","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2024-10-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142491797","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

High-throughput solutions in tumor organoids: From culture to drug screening. 肿瘤器官组织的高通量解决方案：从培养到药物筛选。

IF 4 2区医学

STEM CELLS Pub Date : 2024-10-26 DOI: 10.1093/stmcls/sxae070

Jianing Zuo, Yanhua Fang, Ruoyu Wang, Shan Shan Liang

引用次数: 0

USP13 Overexpression in BMSCs Enhances Anti-Apoptotic Ability and Guards Against Methylprednisolone-Induced Osteonecrosis in Rats. USP13 在 BMSCs 中的过表达可增强抗凋亡能力，防止甲泼尼龙诱导的大鼠骨坏死。

IF 4 2区医学

STEM CELLS Pub Date : 2024-10-26 DOI: 10.1093/stmcls/sxae069

Yixin Jiang, Xiaoli Fan, Yaling Yu, Hongfan Ge, Chengyin Liu, Yanyan Zhang, Lingyun Yu, Wen Yin, Zhenlei Zhou

引用次数: 0

RSPO/LGR signaling regulates proliferation of adult hippocampal neural stem cells. RSPO/LGR 信号调节成体海马神经干细胞的增殖。

IF 4 2区医学

STEM CELLS Pub Date : 2024-10-21 DOI: 10.1093/stmcls/sxae065

Daniela Valenzuela-Bezanilla, Muriel D Mardones, Maximiliano Galassi, Sebastian B Arredondo, Sebastian H Santibanez, Stephanie Gutierrez-Jimenez, Nicolás Merino-Véliz, Fernando J Bustos, Lorena Varela-Nallar

{"title":"RSPO/LGR signaling regulates proliferation of adult hippocampal neural stem cells.","authors":"Daniela Valenzuela-Bezanilla, Muriel D Mardones, Maximiliano Galassi, Sebastian B Arredondo, Sebastian H Santibanez, Stephanie Gutierrez-Jimenez, Nicolás Merino-Véliz, Fernando J Bustos, Lorena Varela-Nallar","doi":"10.1093/stmcls/sxae065","DOIUrl":"https://doi.org/10.1093/stmcls/sxae065","url":null,"abstract":"In the dentate gyrus of the adult hippocampus, neurogenesis from neural stem cells (NSCs) is regulated by Wnt signals from the local microenvironment. The Wnt/β-catenin pathway is active in NSCs, where it regulates proliferation and fate commitment, and subsequently its activity is strongly attenuated. The mechanisms controlling Wnt activity are poorly understood. In stem cells from adult peripheral tissues, secreted R-spondin proteins (RSPO1-4) interact with LGR4-6 receptors and control Wnt signaling strength. Here, we found that RSPO1-3 and LGR4-6 are expressed in the adult dentate gyrus and in cultured NSCs isolated from the adult mouse hippocampus. LGR4-5 expression decreased in cultured NSCs upon differentiation, concomitantly with the reported decrease in Wnt activity. Treatment with RSPO1-3 increased NSC proliferation and the expression of Cyclin D1, but did not induce the expression of Axin2 or RNF43, two well-described Wnt target genes. However, RSPOs enhanced the effect of Wnt3a on Axin2 and RNF43 expression, as well as on Wnt/β-catenin reporter activity, indicating that they can potentiate Wnt activity in NSCs. Moreover, RSPO1-3 were found to be expressed by cultured dentate gyrus astrocytes, a crucial component of the neurogenic niche. In co-culture experiments, the astrocyte-induced proliferation of NSCs was prevented by RSPO2 knockdown in astrocytes and LGR5 knockdown in hippocampal NSCs. Additionally, RSPO2 knockdown in the adult mouse dentate gyrus reduced proliferation of neural stem and progenitor cells in vivo. Altogether, our results indicate that RSPO/LGR signaling is present in the dentate gyrus and plays a crucial role in regulating neural precursor cell proliferation.","PeriodicalId":231,"journal":{"name":"STEM CELLS","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2024-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142454404","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Advantages of Cell Proliferation and Immune Regulation in CD146+NESTIN+ HUMSCs: Insights from Single-Cell RNA Sequencing. CD146+NESTIN+ HUMSCs 的细胞增殖和免疫调节优势：单细胞 RNA 测序的启示。

IF 4 2区医学

STEM CELLS Pub Date : 2024-10-21 DOI: 10.1093/stmcls/sxae063

Peng Huang, Xiaofei Qin, Chuiqin Fan, Huifeng Zhong, Manna Wang, Fuyi Chen, Maochuan Liao, Nanpeng Zheng, Hongwu Wang, Bingchun Lin, Lian Ma

{"title":"Advantages of Cell Proliferation and Immune Regulation in CD146+NESTIN+ HUMSCs: Insights from Single-Cell RNA Sequencing.","authors":"Peng Huang, Xiaofei Qin, Chuiqin Fan, Huifeng Zhong, Manna Wang, Fuyi Chen, Maochuan Liao, Nanpeng Zheng, Hongwu Wang, Bingchun Lin, Lian Ma","doi":"10.1093/stmcls/sxae063","DOIUrl":"https://doi.org/10.1093/stmcls/sxae063","url":null,"abstract":"The heterogeneity of stem cells is a significant factor inhibiting their clinical application, as different cell subpopulations may exhibit substantial differences in biological functions. We performed single-cell sequencing on HUMSCs from three donors of different gestational ages (22 + 5 weeks, 28 weeks, 39 weeks). We also compared the data with single-cell sequencing data from BMSCs from two public databases. The content of CD146+Nestin+ MSCs in preterm HUMSCs (22 + 5W: 30.2%, 28W: 25.8%) was higher than that in full-term HUMSCs (39W: 0.5%) and BMSCs (BMSC1: 0, BMSC2: 0.9%). Cell cycle analysis indicated a higher proportion of cells in the proliferative G2M phase in CD146+Nestin+ MSCs (40.8%) compared to CD146+Nestin- MSCs (20%) and CD146-Nestin- MSCs (12.5%). Degree of differentiation assessment suggested that CD146+Nestin+ MSCs exhibited lower differentiation than other cell subpopulations. Differential gene analysis revealed that CD146+Nestin+ MSCs overexpressed immune regulation-related factors. GO and KEGG enrichment analysis of modules identified by WGCNA suggested enrichment in pathways related to cellular immune regulation, antimicrobial activity, and proliferation. Immune-related gene analysis indicated that CD146+Nestin+ MSCs exhibited expression of multiple immune-related genes associated with \"Antimicrobials,\" \"Cytokines,\" and \"Cytokine Receptors.\" Gene regulatory network analysis revealed high expression of immune-related regulators RELB, GAPB1, and EHF in CD146+Nestin+ MSCs.Our study provides a single-cell atlas of preterm HUMSCs, demonstrating the expression of CD146+Nestin+ MSCs across different tissues and confirming their advantages in cellular proliferation, antimicrobial activity, immune regulation, and low differentiation at the RNA level. This contributes valuable insights for the clinical application of HUMSCs.","PeriodicalId":231,"journal":{"name":"STEM CELLS","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2024-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142454402","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

NLRP3 deficiency improves bone healing of tooth extraction sockets through SMAD2/3-RUNX2 mediated osteoblast differentiation. 缺乏 NLRP3 可通过 SMAD2/3-RUNX2 介导的成骨细胞分化改善拔牙窝的骨愈合。

IF 4 2区医学

STEM CELLS Pub Date : 2024-10-15 DOI: 10.1093/stmcls/sxae064

Ying Geng, Chen Bao, Yue Chen, Ziwei Yan, Fen Miao, Ting Wang, Yingyi Li, Lu Li, Wen Sun, Yan Xu

{"title":"NLRP3 deficiency improves bone healing of tooth extraction sockets through SMAD2/3-RUNX2 mediated osteoblast differentiation.","authors":"Ying Geng, Chen Bao, Yue Chen, Ziwei Yan, Fen Miao, Ting Wang, Yingyi Li, Lu Li, Wen Sun, Yan Xu","doi":"10.1093/stmcls/sxae064","DOIUrl":"https://doi.org/10.1093/stmcls/sxae064","url":null,"abstract":"Impaired bone healing following tooth extraction poses a significant challenge for implantation. As a crucial component of the natural immune system, the NLRP3 inflammasome is one of the most extensively studied Pattern-Recognition Receptors (PRRs), and is involved in multiple diseases. Yet, the role of NLRP3 in bone healing remains to be clarified. Here, to investigate the effect of NLRP3 on bone healing, we established a maxillary first molar extraction model in wild-type (WT) and NLRP3KO mice using minimally invasive techniques. We observed that NLRP3 was activated during the bone repair phase, and its depletion enhanced socket bone formation and osteoblast differentiation. Moreover, NLRP3 inflammasome activation was found to inhibit osteogenic differentiation in alveolar bone-derived mesenchymal stem cells (aBMSCs), an effect mitigated by NLRP3 deficiency. Mechanistically, we established that SMAD2/3-RUNX2 signaling pathway is a downstream target of NLRP3 inflammasome activation, and SMAD2/3 knockdown partially reversed the significant decrease in expression of RUNX2, OSX, and ALP induced by NLRP3. Thus, our findings demonstrate that NLRP3 negatively modulates alveolar socket bone healing and contribute to the understanding of the NLRP3-induced signaling pathways involved in osteogenesis regulation.","PeriodicalId":231,"journal":{"name":"STEM CELLS","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2024-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142454403","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Integrin-linked kinase control dental pulp stem cell senescence via the mTOR signaling pathway. 整合素连接激酶通过 mTOR 信号通路控制牙髓干细胞衰老

IF 4 2区医学

STEM CELLS Pub Date : 2024-10-09 DOI: 10.1093/stmcls/sxae047

Lu Chen, Xiping Wang, Sha Tian, Linxi Zhou, Li Wang, Xiaohan Liu, Zihan Yang, Guiqiang Fu, Xingguang Liu, Chen Ding, Duohong Zou

{"title":"Integrin-linked kinase control dental pulp stem cell senescence via the mTOR signaling pathway.","authors":"Lu Chen, Xiping Wang, Sha Tian, Linxi Zhou, Li Wang, Xiaohan Liu, Zihan Yang, Guiqiang Fu, Xingguang Liu, Chen Ding, Duohong Zou","doi":"10.1093/stmcls/sxae047","DOIUrl":"10.1093/stmcls/sxae047","url":null,"abstract":"Human dental pulp stem cells (HDPSCs) showed an age-dependent decline in proliferation and differentiation capacity. Decline in proliferation and differentiation capacity affects the dental stromal tissue homeostasis and impairs the regenerative capability of HDPSCs. However, which age-correlated proteins regulate the senescence of HDPSCs remain unknown. Our study investigated the proteomic characteristics of HDPSCs isolated from subjects of different ages and explored the molecular mechanism of age-related changes in HDPSCs. Our study showed that the proliferation and osteogenic differentiation of HDPSCs were decreased, while the expression of aging-related genes (p21, p53) and proportion of senescence-associated β-galactosidase (SA-β-gal)-positive cells were increased with aging. The bioinformatic analysis identified that significant proteins positively correlated with age were enriched in response to the mammalian target of rapamycin (mTOR) signaling pathway (ILK, MAPK3, mTOR, STAT1, and STAT3). We demonstrated that OSU-T315, an inhibitor of integrin-linked kinase (ILK), rejuvenated aged HDPSCs, similar to rapamycin (an inhibitor of mTOR). Treatment with OSU-T315 decreased the expression of aging-related genes (p21, p53) and proportion of SA-β-gal-positive cells in HDPSCs isolated from old (O-HDPSCs). Additionally, OSU-T315 promoted the osteoblastic differentiation capacity of O-HDPSCs in vitro and bone regeneration of O-HDPSCs in rat calvarial bone defects model. Our study indicated that the proliferation and osteoblastic differentiation of HDPSCs were impaired with aging. Notably, the ILK/AKT/mTOR/STAT1 signaling pathway may be a major factor in the regulation of HDPSC senescence, which help to provide interventions for HDPSC senescence.","PeriodicalId":231,"journal":{"name":"STEM CELLS","volume":" ","pages":"861-873"},"PeriodicalIF":4.0,"publicationDate":"2024-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11464141/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142015888","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

TMEM16A regulates satellite cell-mediated skeletal muscle regeneration by ensuring a moderate level of caspase 3 activity. TMEM16A 通过确保适度的 Caspase 3 活性来调节卫星细胞介导的骨骼肌再生。

IF 4 2区医学

STEM CELLS Pub Date : 2024-10-09 DOI: 10.1093/stmcls/sxae048

Zhiyuan Sun, Xinqi Shan, Chun'e Fan, Lutao Liu, Shuai Li, Jiahui Wang, Na Zhou, Minsheng Zhu, Huaqun Chen

{"title":"TMEM16A regulates satellite cell-mediated skeletal muscle regeneration by ensuring a moderate level of caspase 3 activity.","authors":"Zhiyuan Sun, Xinqi Shan, Chun'e Fan, Lutao Liu, Shuai Li, Jiahui Wang, Na Zhou, Minsheng Zhu, Huaqun Chen","doi":"10.1093/stmcls/sxae048","DOIUrl":"10.1093/stmcls/sxae048","url":null,"abstract":"It has been documented that caspase 3 activity is necessary for skeletal muscle regeneration, but how its activity is regulated is largely unknown. Our previous report shows that intracellular TMEM16A, a calcium activated chloride channel, significantly regulates caspase 3 activity in myoblasts during skeletal muscle development. By using a mouse line with satellite cell (SC)-specific deletion of TMEM16A, we examined the role of TMEM16A in regulating caspase 3 activity in SC (or SC-derived myoblast) as well as skeletal muscle regeneration. The mutant animals displayed apparently impaired regeneration capacity in adult muscle along with enhanced ER stress and elevated caspase 3 activity in Tmem16a-/- SC derived myoblasts. Blockade of either excessive ER stress or caspase 3 activity by small molecules significantly restored the inhibited myogenic differentiation of Tmem16a-/- SCs, indicating that excessive caspase 3 activity resulted from TMEM16A deletion contributes to the impaired muscle regeneration and the upstream regulator of caspase 3 was ER stress. Our results revealed an essential role of TMEM16A in satellite cell-mediated skeletal muscle regeneration by ensuring a moderate level of caspase 3 activity.","PeriodicalId":231,"journal":{"name":"STEM CELLS","volume":" ","pages":"902-913"},"PeriodicalIF":4.0,"publicationDate":"2024-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141887741","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0