Cell stem cell最新文献_第8页

Enhanced viability and functional maturity of iPSC-derived islet organoids by collagen-VI-enriched ECM scaffolds 利用富含胶原vi的ECM支架增强ipsc衍生的胰岛类器官的活力和功能成熟度

IF 23.9 1区医学

Cell stem cell Pub Date : 2025-02-24 DOI: 10.1016/j.stem.2025.02.001

Deliang Zhu, Zixin Chen, Kaimin Guo, Qingqiang Xie, Yuxiu Zou, Qizheng Mou, Zhongjun Zhou, Guoxiang Jin

{"title":"Enhanced viability and functional maturity of iPSC-derived islet organoids by collagen-VI-enriched ECM scaffolds","authors":"Deliang Zhu, Zixin Chen, Kaimin Guo, Qingqiang Xie, Yuxiu Zou, Qizheng Mou, Zhongjun Zhou, Guoxiang Jin","doi":"10.1016/j.stem.2025.02.001","DOIUrl":"https://doi.org/10.1016/j.stem.2025.02.001","url":null,"abstract":"Islet organoids derived from pluripotent stem cells offer a promising solution for the shortage of cadaveric donors in diabetes treatment. However, challenges remain in improving their differentiation, viability, functional maturity, and engraftment. Here, we generated improved islet organoids with high viability and functionality by employing extracellular matrix (ECM) hydrogel of decellularized amniotic membrane (dAM). The dAM sheet facilitates islet organoid engraftment and rapidly restores normoglycemia in diabetic mice, accompanied by increased body weight and augmented insulin release in response to glucose. Interestingly, collagen VI (Col VI) was identified as a key component of islet niche, enhancing islet cell viability and biological function. Col-VI-based biomimetic ECM recapitulates the native environment and exhibits superior physiological properties. Importantly, the cellular composition and endocrine function of optimized induced pluripotent stem cell (iPSC)-derived islet organoids are comparable with those of human islets. Our findings offer a valuable platform for future endeavors in organoid-transplantation-based therapy of diabetes.","PeriodicalId":9665,"journal":{"name":"Cell stem cell","volume":"65 1","pages":""},"PeriodicalIF":23.9,"publicationDate":"2025-02-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143477375","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}

引用次数: 0

Systems immunology analysis of human immune organoids identifies host-specific correlates of protection to different influenza vaccines 人类免疫类器官的系统免疫学分析确定了对不同流感疫苗保护的宿主特异性相关因子

IF 23.9 1区医学

Cell stem cell Pub Date : 2025-02-21 DOI: 10.1016/j.stem.2025.01.014

Zachary W. Wagoner, Timothy B. Yates, Jenny E. Hernandez-Davies, Suhas Sureshchandra, Erika M. Joloya, Aarti Jain, Rafael de Assis, Jenna M. Kastenschmidt, Andrew M. Sorn, Mahina Tabassum Mitul, Ian Tamburini, Gurpreet Ahuja, Qiu Zhong, Douglas Trask, Marcus Seldin, D. Huw Davies, Lisa E. Wagar

{"title":"Systems immunology analysis of human immune organoids identifies host-specific correlates of protection to different influenza vaccines","authors":"Zachary W. Wagoner, Timothy B. Yates, Jenny E. Hernandez-Davies, Suhas Sureshchandra, Erika M. Joloya, Aarti Jain, Rafael de Assis, Jenna M. Kastenschmidt, Andrew M. Sorn, Mahina Tabassum Mitul, Ian Tamburini, Gurpreet Ahuja, Qiu Zhong, Douglas Trask, Marcus Seldin, D. Huw Davies, Lisa E. Wagar","doi":"10.1016/j.stem.2025.01.014","DOIUrl":"https://doi.org/10.1016/j.stem.2025.01.014","url":null,"abstract":"Vaccines are an essential tool to significantly reduce pathogen-related morbidity and mortality. However, our ability to rationally design vaccines and identify correlates of protection remains limited. Here, we employed an immune organoid approach to capture human adaptive immune response diversity to influenza vaccines and systematically identify host and antigen features linked to vaccine response variability. Our investigation identified established and unique immune signatures correlated with neutralizing antibody responses across seven different influenza vaccines and antigens. Unexpectedly, heightened ex vivo tissue frequencies of T helper (Th)1 cells emerged as both a predictor and a correlate of neutralizing antibody responses to inactivated influenza vaccines (IIVs). Secondary analysis of human public data confirmed that elevated Th1 signatures are associated with antibody responses following in vivo vaccination. These findings demonstrate the utility of human in vitro models for identifying in vivo correlates of protection and establish a role for Th1 functions in influenza vaccination.","PeriodicalId":9665,"journal":{"name":"Cell stem cell","volume":"22 1","pages":""},"PeriodicalIF":23.9,"publicationDate":"2025-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143463094","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}

引用次数: 0

Mechano-oncogenic cytoskeletal remodeling drives leukemic transformation with mitochondrial vesicle-mediated STING activation 机械致癌细胞骨架重塑通过线粒体囊泡介导的STING激活驱动白血病转化

IF 23.9 1区医学

Cell stem cell Pub Date : 2025-02-21 DOI: 10.1016/j.stem.2025.01.013

Zemin Song, Yali Cui, Lilan Xin, Ruijing Xiao, Jingjing Feng, Conghui Li, Zhinang Yin, Honghong Wang, Qiuzi Li, Mengxuan Wang, Baoyi Lin, Yiming Zhang, Ying Zhou, Li Huang, Yanli He, Xiaoqing Li, Xiaoyan Liu, Shangqin Liu, Fuling Zhou, Zheng Liu, Kaiwei Liang

{"title":"Mechano-oncogenic cytoskeletal remodeling drives leukemic transformation with mitochondrial vesicle-mediated STING activation","authors":"Zemin Song, Yali Cui, Lilan Xin, Ruijing Xiao, Jingjing Feng, Conghui Li, Zhinang Yin, Honghong Wang, Qiuzi Li, Mengxuan Wang, Baoyi Lin, Yiming Zhang, Ying Zhou, Li Huang, Yanli He, Xiaoqing Li, Xiaoyan Liu, Shangqin Liu, Fuling Zhou, Zheng Liu, Kaiwei Liang","doi":"10.1016/j.stem.2025.01.013","DOIUrl":"https://doi.org/10.1016/j.stem.2025.01.013","url":null,"abstract":"Mitochondria are integrated within the cytoskeleton for structural integrity and functional regulation, yet the pathological exploitation of these interactions in cell fate decisions remains largely unexplored. Here, we identify a cytoskeleton-mitochondria remodeling mechanism underlying leukemic transformation by the core-binding factor subunit beta and smooth muscle myosin heavy-chain fusion (CBFβ-SMMHC). This chimera reconstructs a cytosolic filamentous cytoskeleton, inducing NMIIA phosphorylation and INF2-dependent filamentous actin (F-actin) assembly, which enhance cellular stiffness and tension, leading to calcium-mediated mitochondrial constriction, termed cytoskeletal co-option of mitochondrial constriction (CCMC). CCMC can also be triggered through diverse approaches independent of CBFβ-SMMHC, reconstructing a similar cytoskeleton and recapitulating acute myeloid leukemia (AML) with consistent immunophenotypes and inflammatory signatures. Notably, CCMC generates TOM20−PDH+mtDNA+ mitochondrial-derived vesicles that activate cGAS-STING signaling, with Sting knockout abrogating CCMC-induced leukemogenesis. Targeted inhibition of CCMC or STING suppresses AML propagation while sparing normal hematopoiesis. These findings establish CCMC as an intrinsic mechano-oncogenic process linking genetic mutations with cytoskeletal remodeling to oncogenic transformation, highlighting its promise as a therapeutic target.","PeriodicalId":9665,"journal":{"name":"Cell stem cell","volume":"54 1","pages":""},"PeriodicalIF":23.9,"publicationDate":"2025-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143463093","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}

引用次数: 0

Sustained NF-κB activation allows mutant alveolar stem cells to co-opt a regeneration program for tumor initiation 持续的NF-κB激活允许突变的肺泡干细胞参与肿瘤起始的再生程序

IF 23.9 1区医学

Cell stem cell Pub Date : 2025-02-19 DOI: 10.1016/j.stem.2025.01.011

Frances J. England, Ignacio Bordeu, Minn-E. Ng, JaeHak Bang, Bumsoo Kim, Jinwook Choi, Erik C. Cardoso, Bon-Kyoung Koo, Benjamin D. Simons, Joo-Hyeon Lee

引用次数: 0

PSPC1 exerts an oncogenic role in AML by regulating a leukemic transcription program in cooperation with PU.1 PSPC1通过与PU.1合作调节白血病转录程序，在AML中发挥致瘤作用

IF 23.9 1区医学

Cell stem cell Pub Date : 2025-02-14 DOI: 10.1016/j.stem.2025.01.010

Juyeong Hong, Pinpin Sui, Ying Li, Kerryn Y. Xu, Ji-Hoon Lee, Juan Wang, Shi Chen, Peng Zhang, Noah Wingate, Asra Noor, Yaxia Yuan, Robert Hromas, Hongwei Zhou, Karina Hamamoto, Rui Su, C. Cameron Yin, Fengxi Ye, Andrés E. Quesada, Jianjun Chen, Suming Huang, Mingjiang Xu

{"title":"PSPC1 exerts an oncogenic role in AML by regulating a leukemic transcription program in cooperation with PU.1","authors":"Juyeong Hong, Pinpin Sui, Ying Li, Kerryn Y. Xu, Ji-Hoon Lee, Juan Wang, Shi Chen, Peng Zhang, Noah Wingate, Asra Noor, Yaxia Yuan, Robert Hromas, Hongwei Zhou, Karina Hamamoto, Rui Su, C. Cameron Yin, Fengxi Ye, Andrés E. Quesada, Jianjun Chen, Suming Huang, Mingjiang Xu","doi":"10.1016/j.stem.2025.01.010","DOIUrl":"https://doi.org/10.1016/j.stem.2025.01.010","url":null,"abstract":"Acute myeloid leukemia (AML) is an aggressive hematopoietic malignancy characterized by the blockage of myeloid cell differentiation and uncontrolled proliferation of immature myeloid cells. Here, we show that paraspeckle component 1 (PSPC1) is aberrantly overexpressed and associated with poor survival in AML patients. Using human AML cells and mouse models, we demonstrate that PSPC1 is not required for normal hematopoiesis, but it is critical and essential for AML cells to maintain their leukemic characteristics. PSPC1 loss induces robust differentiation, suppresses proliferation, and abolishes leukemogenesis in diverse AML cells. Mechanistically, PSPC1 exerts a pro-leukemia effect by regulating a unique leukemic transcription program via cooperative chromatin binding with PU.1 and activation of tumor-promoting genes, including NDC1, which is not previously implicated in AML. Our findings uncover a unique and crucial role of PSPC1 dependency in AML and highlight its potential as a promising therapeutic target for AML.","PeriodicalId":9665,"journal":{"name":"Cell stem cell","volume":"18 1 1","pages":""},"PeriodicalIF":23.9,"publicationDate":"2025-02-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143417697","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}

引用次数: 0

Pre-clinical safety and efficacy of human induced pluripotent stem cell-derived products for autologous cell therapy in Parkinson’s disease 人类诱导多能干细胞衍生产品用于帕金森病自体细胞治疗的临床前安全性和有效性

IF 23.9 1区医学

Cell stem cell Pub Date : 2025-02-13 DOI: 10.1016/j.stem.2025.01.006

Jeha Jeon, Young Cha, Yean Ju Hong, In-Hee Lee, Heejin Jang, Sanghyeok Ko, Serhiy Naumenko, Minseon Kim, Hannah L. Ryu, Zenith Shrestha, Nayeon Lee, Tae-Yoon Park, HoeWon Park, Seo-Hyun Kim, Ki-Jun Yoon, Bin Song, Jeffrey Schweitzer, Todd M. Herrington, Sek Won Kong, Bob Carter, Kwang-Soo Kim

{"title":"Pre-clinical safety and efficacy of human induced pluripotent stem cell-derived products for autologous cell therapy in Parkinson’s disease","authors":"Jeha Jeon, Young Cha, Yean Ju Hong, In-Hee Lee, Heejin Jang, Sanghyeok Ko, Serhiy Naumenko, Minseon Kim, Hannah L. Ryu, Zenith Shrestha, Nayeon Lee, Tae-Yoon Park, HoeWon Park, Seo-Hyun Kim, Ki-Jun Yoon, Bin Song, Jeffrey Schweitzer, Todd M. Herrington, Sek Won Kong, Bob Carter, Kwang-Soo Kim","doi":"10.1016/j.stem.2025.01.006","DOIUrl":"https://doi.org/10.1016/j.stem.2025.01.006","url":null,"abstract":"Human induced pluripotent stem cell (hiPSC)-derived midbrain dopaminergic cells (mDACs) represent a promising source for autologous cell therapy in Parkinson’s disease (PD), but standardized regulatory criteria are essential for clinical translation. In this pre-clinical study, we generated multiple clinical-grade hiPSC lines from freshly biopsied fibroblasts of four sporadic PD patients using episomal reprogramming and differentiated them into mDACs using a refined 21-day protocol. Rigorous evaluations included whole-genome/exome sequencing, RNA sequencing, and in vivo studies, including a 39-week Good Laboratory Practice-compliant mouse safety study. While mDACs from all lines met safety criteria, mDACs from one patient failed to improve rodent behavioral outcomes, underscoring inter-individual variability. Importantly, in vitro assessments did not reliably predict in vivo efficacy, identifying dopaminergic fiber density as a key efficacy criterion. These findings support comprehensive quality control guidelines for autologous cell therapy and pave the way for a clinical trial with eight sporadic PD patients, scheduled to commence in 2025.","PeriodicalId":9665,"journal":{"name":"Cell stem cell","volume":"78 1","pages":""},"PeriodicalIF":23.9,"publicationDate":"2025-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143401335","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}

引用次数: 0

Individualized patient tumor organoids faithfully preserve human brain tumor ecosystems and predict patient response to therapy 个体化患者肿瘤类器官忠实地保存人类脑肿瘤生态系统并预测患者对治疗的反应

IF 23.9 1区医学

Cell stem cell Pub Date : 2025-02-11 DOI: 10.1016/j.stem.2025.01.002

Tianping Peng, Xiujian Ma, Wei Hua, Changwen Wang, Youjun Chu, Meng Sun, Valentina Fermi, Stefan Hamelmann, Katharina Lindner, Chunxuan Shao, Julia Zaman, Weili Tian, Yue Zhuo, Yassin Harim, Nadja Stöffler, Linda Hammann, Qungen Xiao, Xiaoliang Jin, Rolf Warta, Catharina Lotsch, Ying Mao

{"title":"Individualized patient tumor organoids faithfully preserve human brain tumor ecosystems and predict patient response to therapy","authors":"Tianping Peng, Xiujian Ma, Wei Hua, Changwen Wang, Youjun Chu, Meng Sun, Valentina Fermi, Stefan Hamelmann, Katharina Lindner, Chunxuan Shao, Julia Zaman, Weili Tian, Yue Zhuo, Yassin Harim, Nadja Stöffler, Linda Hammann, Qungen Xiao, Xiaoliang Jin, Rolf Warta, Catharina Lotsch, Ying Mao","doi":"10.1016/j.stem.2025.01.002","DOIUrl":"https://doi.org/10.1016/j.stem.2025.01.002","url":null,"abstract":"Tumor organoids are important tools for cancer research, but current models have drawbacks that limit their applications for predicting response to therapy. Here, we developed a fast, efficient, and complex culture system (IPTO, individualized patient tumor organoid) that accurately recapitulates the cellular and molecular pathology of human brain tumors. Patient-derived tumor explants were cultured in induced pluripotent stem cell (iPSC)-derived cerebral organoids, thus enabling culture of a wide range of human tumors in the central nervous system (CNS), including adult, pediatric, and metastatic brain cancers. Histopathological, genomic, epigenomic, and single-cell RNA sequencing (scRNA-seq) analyses demonstrated that the IPTO model recapitulates cellular heterogeneity and molecular features of original tumors. Crucially, we showed that the IPTO model predicts patient-specific drug responses, including resistance mechanisms, in a prospective patient cohort. Collectively, the IPTO model represents a major breakthrough in preclinical modeling of human cancers, which provides a path toward personalized cancer therapy.","PeriodicalId":9665,"journal":{"name":"Cell stem cell","volume":"86 1","pages":""},"PeriodicalIF":23.9,"publicationDate":"2025-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143385072","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}

引用次数: 0

Cognitive impairment in epilepsy progression: Adult neurogenesis loss at critical window 癫痫进展中的认知障碍：关键窗口期成人神经发生丧失

IF 23.9 1区医学

Cell stem cell Pub Date : 2025-02-06 DOI: 10.1016/j.stem.2025.01.004

Yi Wang, Zhong Chen

引用次数: 0

Human iPSCs offer an alternative for modeling vascular malformation 人类多能干细胞为血管畸形建模提供了另一种选择

IF 23.9 1区医学

Cell stem cell Pub Date : 2025-02-06 DOI: 10.1016/j.stem.2025.01.008

Stefanie DeFronzo, Guohao Dai

引用次数: 0

Neural stem cell quiescence and activation dynamics are regulated by feedback input from their progeny under homeostatic and regenerative conditions 在稳态和再生条件下，神经干细胞的静止和激活动力学是由其后代的反馈输入调节的

IF 23.9 1区医学

Cell stem cell Pub Date : 2025-02-06 DOI: 10.1016/j.stem.2025.01.001

Alina Marymonchyk, Raquel Rodriguez-Aller, Ashleigh Willis, Frédéric Beaupré, Sareen Warsi, Marina Snapyan, Valérie Clavet-Fournier, Flavie Lavoie-Cardinal, David R. Kaplan, Freda D. Miller, Armen Saghatelyan

{"title":"Neural stem cell quiescence and activation dynamics are regulated by feedback input from their progeny under homeostatic and regenerative conditions","authors":"Alina Marymonchyk, Raquel Rodriguez-Aller, Ashleigh Willis, Frédéric Beaupré, Sareen Warsi, Marina Snapyan, Valérie Clavet-Fournier, Flavie Lavoie-Cardinal, David R. Kaplan, Freda D. Miller, Armen Saghatelyan","doi":"10.1016/j.stem.2025.01.001","DOIUrl":"https://doi.org/10.1016/j.stem.2025.01.001","url":null,"abstract":"Life-long maintenance of stem cells implies that feedback mechanisms from the niche regulate their quiescence/activation dynamics. Here, in the mouse adult subventricular neural stem cell (NSC) niche, we charted a precise spatiotemporal map of functional responses in NSCs induced by multiple niche cells and used machine learning to predict NSC interactions with specific niche cell types. We revealed a feedback mechanism whereby the NSC proliferative state is directly repressed by transient amplifying cells (TAPs), their rapidly dividing progeny. NSC processes wrap around TAPs and display hotspots of Ca2+ activity at their points of contact, mediated by ephrin (Efn) signaling. The modulation of Efn signaling or TAP ablation altered the Ca2+ signature of NSCs, leading to their activation. In vivo optogenetic modulation of Ca2+ dynamics abrogated NSC activation and prevented niche replenishment. Thus, TAP-to-NSC feedback signaling controls stem cell quiescence and activation, providing a mechanism to maintain stem cell pools throughout life.","PeriodicalId":9665,"journal":{"name":"Cell stem cell","volume":"42 1","pages":""},"PeriodicalIF":23.9,"publicationDate":"2025-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143192640","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}

引用次数: 0