Cell stem cell最新文献_第7页

Embryonic macrophages support endocrine commitment during human pancreatic differentiation 胚胎巨噬细胞支持人类胰腺分化过程中的内分泌承诺

IF 23.9 1区医学

Cell stem cell Pub Date : 2024-10-14 DOI: 10.1016/j.stem.2024.09.011

Adriana Migliorini, Sabrina Ge, Michael H. Atkins, Amanda Oakie, Rangarajan Sambathkumar, Gregory Kent, Haiyang Huang, Angel Sing, Conan Chua, Adam J. Gehring, Gordon M. Keller, Faiyaz Notta, Maria Cristina Nostro

{"title":"Embryonic macrophages support endocrine commitment during human pancreatic differentiation","authors":"Adriana Migliorini, Sabrina Ge, Michael H. Atkins, Amanda Oakie, Rangarajan Sambathkumar, Gregory Kent, Haiyang Huang, Angel Sing, Conan Chua, Adam J. Gehring, Gordon M. Keller, Faiyaz Notta, Maria Cristina Nostro","doi":"10.1016/j.stem.2024.09.011","DOIUrl":"https://doi.org/10.1016/j.stem.2024.09.011","url":null,"abstract":"Organogenesis is a complex process that relies on a dynamic interplay between extrinsic factors originating from the microenvironment and tissue-specific intrinsic factors. For pancreatic endocrine cells, the local niche consists of acinar and ductal cells as well as neuronal, immune, endothelial, and stromal cells. Hematopoietic cells have been detected in human pancreas as early as 6 post-conception weeks, but whether they play a role during human endocrinogenesis remains unknown. To investigate this, we performed single-nucleus RNA sequencing (snRNA-seq) of the second-trimester human pancreas and identified a wide range of hematopoietic cells, including two distinct subsets of tissue-resident macrophages. Leveraging this discovery, we developed a co-culture system of human embryonic stem cell-derived endocrine-macrophage organoids to model their interaction in vitro. Here, we show that macrophages support the differentiation and viability of endocrine cells in vitro and enhance tissue engraftment, highlighting their potential role in tissue engineering strategies for diabetes.","PeriodicalId":9665,"journal":{"name":"Cell stem cell","volume":"11 1","pages":""},"PeriodicalIF":23.9,"publicationDate":"2024-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142431233","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

Effective regulatory responses to predatory stem cell markets in Australia and Canada 澳大利亚和加拿大针对掠夺性干细胞市场的有效监管对策

IF 23.9 1区医学

Cell stem cell Pub Date : 2024-10-03 DOI: 10.1016/j.stem.2024.09.007

Laertis Ikonomou, Megan Munsie, Carl Power, Douglas Sipp, Leigh Turner, John E.J. Rasko

引用次数: 0

Let’s get functional: Drug sensitivity profiling to enable precision sarcoma medicine 让我们发挥功能：通过药物敏感性分析实现肉瘤精准医疗

IF 23.9 1区医学

Cell stem cell Pub Date : 2024-10-03 DOI: 10.1016/j.stem.2024.09.006

Claudia R. Ball, Stefan Fröhling

引用次数: 0

Common and uncommon findings in marmoset and human trophoblast stem cells 狨猴和人类滋养层干细胞的常见和不常见发现

IF 23.9 1区医学

Cell stem cell Pub Date : 2024-10-03 DOI: 10.1016/j.stem.2024.07.008

Hiroaki Okae, Shun Shibata, Takahiro Arima

引用次数: 0

Charles “Chuck” K.F. Chan (1975–2024) 陈国辉（1975-2024）

IF 23.9 1区医学

Cell stem cell Pub Date : 2024-10-03 DOI: 10.1016/j.stem.2024.09.005

Thomas H. Ambrosi, Michael T. Longaker

引用次数: 0

Early human development and stem cell-based human embryo models 人类早期发育和基于干细胞的人类胚胎模型

IF 23.9 1区医学

Cell stem cell Pub Date : 2024-10-03 DOI: 10.1016/j.stem.2024.09.002

Marta N. Shahbazi, Vincent Pasque

引用次数: 0

Selective translation of nuclear mitochondrial respiratory proteins reprograms succinate metabolism in AML development and chemoresistance 核线粒体呼吸蛋白的选择性翻译重塑了琥珀酸代谢在急性髓细胞性白血病发展和化疗抗药性过程中的作用

IF 23.9 1区医学

Cell stem cell Pub Date : 2024-10-01 DOI: 10.1016/j.stem.2024.09.008

Guoqiang Han, Manman Cui, Pengbo Lu, Tiantian Zhang, Rong Yin, Jin Hu, Jihua Chai, Jing Wang, Kexin Gao, Weidong Liu, Shuxin Yao, Ziyan Cao, Yanbing Zheng, Wen Tian, Rongxia Guo, Min Shen, Zheming Liu, Weiming Li, Shanshan Zhao, Xiangpeng Lin, Haojian Zhang

{"title":"Selective translation of nuclear mitochondrial respiratory proteins reprograms succinate metabolism in AML development and chemoresistance","authors":"Guoqiang Han, Manman Cui, Pengbo Lu, Tiantian Zhang, Rong Yin, Jin Hu, Jihua Chai, Jing Wang, Kexin Gao, Weidong Liu, Shuxin Yao, Ziyan Cao, Yanbing Zheng, Wen Tian, Rongxia Guo, Min Shen, Zheming Liu, Weiming Li, Shanshan Zhao, Xiangpeng Lin, Haojian Zhang","doi":"10.1016/j.stem.2024.09.008","DOIUrl":"https://doi.org/10.1016/j.stem.2024.09.008","url":null,"abstract":"Mitochondrial adaptations dynamically reprogram cellular bioenergetics and metabolism and confer key properties for human cancers. However, the selective regulation of these mitochondrial responses remains largely elusive. Here, inspired by a genetic screening in acute myeloid leukemia (AML), we identify RAS effector RREB1 as a translational regulator and uncover a unique translation control system for nuclear-encoded mitochondrial proteins in human cancers. RREB1 deletion reduces mitochondrial activities and succinate metabolism, thereby damaging leukemia stem cell (LSC) function and AML development. Replenishing complex II subunit SDHD rectifies these deficiencies. Notably, inhibition of complex II re-sensitizes AML cells to venetoclax treatment. Mechanistically, a short RREB1 variant binds to a conserved motif in the 3′ UTRs and cooperates with elongation factor eEF1A1 to enhance protein translation of nuclear-encoded mitochondrial mRNAs. Overall, our findings reveal a unique translation control mechanism for mitochondrial adaptations in AML pathogenesis and provide a potential strategy for targeting this vulnerability of LSCs.","PeriodicalId":9665,"journal":{"name":"Cell stem cell","volume":"12 1","pages":""},"PeriodicalIF":23.9,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142360191","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

A human organoid drug screen identifies α2-adrenergic receptor signaling as a therapeutic target for cartilage regeneration 人体类器官药物筛选确定α2-肾上腺素能受体信号传导是软骨再生的治疗靶点

IF 23.9 1区医学

Cell stem cell Pub Date : 2024-09-30 DOI: 10.1016/j.stem.2024.09.001

Xiaocui Wei, Jingyang Qiu, Ruijun Lai, Tiantian Wei, Zhijie Lin, Shijiang Huang, Yuanjun Jiang, Zhanpeng Kuang, Hao Zeng, Yan Gong, Xiaoling Xie, Jun Yang, Yue Zhang, Sheng Zhang, Zhipeng Zou, Xuefei Gao, Xiaochun Bai

{"title":"A human organoid drug screen identifies α2-adrenergic receptor signaling as a therapeutic target for cartilage regeneration","authors":"Xiaocui Wei, Jingyang Qiu, Ruijun Lai, Tiantian Wei, Zhijie Lin, Shijiang Huang, Yuanjun Jiang, Zhanpeng Kuang, Hao Zeng, Yan Gong, Xiaoling Xie, Jun Yang, Yue Zhang, Sheng Zhang, Zhipeng Zou, Xuefei Gao, Xiaochun Bai","doi":"10.1016/j.stem.2024.09.001","DOIUrl":"https://doi.org/10.1016/j.stem.2024.09.001","url":null,"abstract":"Directed differentiation of stem cells toward chondrogenesis in vitro and in situ to regenerate cartilage suffers from off-target differentiation and hypertrophic tendency. Here, we generated a cartilaginous organoid system from human expanded pluripotent stem cells (hEPSCs) carrying a COL2A1mCherry and COL10A1eGFP double reporter, enabling real-time monitoring of chondrogenesis and hypertrophy. After screening 2,040 FDA-approved drugs, we found that α-adrenergic receptor (α-AR) antagonists, especially phentolamine, stimulated chondrogenesis but repressed hypertrophy, while α2-AR agonists reduced chondrogenesis and induced hypertrophy. Phentolamine prevented cartilage degeneration in hEPSC cartilaginous organoid and human cartilage explant models and stimulated microfracture-activated endogenous skeletal stem cells toward hyaline-like cartilage regeneration without fibrotic degeneration in situ. Mechanistically, α2-AR signaling induced hypertrophic degeneration via cyclic guanosine monophosphate (cGMP)-dependent secretory leukocyte protease inhibitor (SLPI) production. SLPI-deleted cartilaginous organoid was degeneration resistant, facilitating large cartilage defect healing. Ultimately, targeting α2-AR/SLPI was a promising and clinically feasible strategy to regenerate cartilage via promoting chondrogenesis and repressing hypertrophy.","PeriodicalId":9665,"journal":{"name":"Cell stem cell","volume":"40 1","pages":""},"PeriodicalIF":23.9,"publicationDate":"2024-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142330145","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

Epitope prime editing shields hematopoietic cells from CD123 immunotherapy for acute myeloid leukemia 表位素编辑可保护造血细胞免受治疗急性髓性白血病的 CD123 免疫疗法的影响

IF 23.9 1区医学

Cell stem cell Pub Date : 2024-09-30 DOI: 10.1016/j.stem.2024.09.003

Rui-Jin Ji, Guo-Hua Cao, Wei-Qiang Zhao, Mu-Yao Wang, Pan Gao, Yi-Zhou Zhang, Xue-Bin Wang, Hou-Yuan Qiu, Di-Di Chen, Xiao-Han Tong, Min Duan, Hao Yin, Ying Zhang

{"title":"Epitope prime editing shields hematopoietic cells from CD123 immunotherapy for acute myeloid leukemia","authors":"Rui-Jin Ji, Guo-Hua Cao, Wei-Qiang Zhao, Mu-Yao Wang, Pan Gao, Yi-Zhou Zhang, Xue-Bin Wang, Hou-Yuan Qiu, Di-Di Chen, Xiao-Han Tong, Min Duan, Hao Yin, Ying Zhang","doi":"10.1016/j.stem.2024.09.003","DOIUrl":"https://doi.org/10.1016/j.stem.2024.09.003","url":null,"abstract":"Acute myeloid leukemia (AML) is a malignant cancer characterized by abnormal differentiation of hematopoietic stem and progenitor cells (HSPCs). While chimeric antigen receptor T (CAR-T) cell immunotherapies target AML cells, they often induce severe on-target/off-tumor toxicity by attacking normal cells expressing the same antigen. Here, we used base editors (BEs) and a prime editor (PE) to modify the epitope of CD123 on HSPCs, protecting healthy cells from CAR-T-induced cytotoxicity while maintaining their normal function. Although BE effectively edits epitopes, complex bystander products are a concern. To enhance precision, we optimized prime editing, increasing the editing efficiency from 5.9% to 78.9% in HSPCs. Epitope-modified cells were resistant to CAR-T lysis while retaining normal differentiation and function. Furthermore, BE- or PE-edited HSPCs infused into humanized mice endowed myeloid lineages with selective resistance to CAR-T immunotherapy, demonstrating a proof-of-concept strategy for treating relapsed AML.","PeriodicalId":9665,"journal":{"name":"Cell stem cell","volume":"39 1","pages":""},"PeriodicalIF":23.9,"publicationDate":"2024-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142330271","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

Multiplex CRISPR/Cas9-Based Genome Editing in Human Hematopoietic Stem Cells Models Clonal Hematopoiesis and Myeloid Neoplasia 基于多重 CRISPR/Cas9 基因组编辑的人类造血干细胞克隆性造血和骨髓性肿瘤模型

IF 23.9 1区医学

Cell stem cell Pub Date : 2024-09-24 DOI: 10.1016/j.stem.2024.09.012

Zuzana Tothova, John M. Krill-Burger, Katerina D. Popova, Catherine C. Landers, Quinlan L. Sievers, David Yudovich, Roger Belizaire, Jon C. Aster, Elizabeth A. Morgan, Aviad Tsherniak, Benjamin L. Ebert

引用次数: 0