Cell stem cell最新文献

To play Paneth or goblet: Shapeshifting secretory cells read the room 玩潘尼斯或高脚杯：变形分泌细胞读取房间

IF 23.9 1区医学

Cell stem cell Pub Date : 2025-06-18 DOI: 10.1016/j.stem.2025.06.007

Irene V. Choi, Rachel K. Zwick

引用次数: 0

Rapid generation of functional vascular organoids via simultaneous transcription factor activation of endothelial and mural lineages 通过内皮和壁系同时激活转录因子快速生成功能性血管类器官

IF 23.9 1区医学

Cell stem cell Pub Date : 2025-06-13 DOI: 10.1016/j.stem.2025.05.014

Liyan Gong, Yadong Zhang, Yonglin Zhu, Umji Lee, Allen Chilun Luo, Xiang Li, Xi Wang, Danyang Chen, William T. Pu, Ruei-Zeng Lin, Minglin Ma, Miao Cui, Kaifu Chen, Kai Wang, Juan M. Melero-Martin

{"title":"Rapid generation of functional vascular organoids via simultaneous transcription factor activation of endothelial and mural lineages","authors":"Liyan Gong, Yadong Zhang, Yonglin Zhu, Umji Lee, Allen Chilun Luo, Xiang Li, Xi Wang, Danyang Chen, William T. Pu, Ruei-Zeng Lin, Minglin Ma, Miao Cui, Kaifu Chen, Kai Wang, Juan M. Melero-Martin","doi":"10.1016/j.stem.2025.05.014","DOIUrl":"https://doi.org/10.1016/j.stem.2025.05.014","url":null,"abstract":"Vascular organoids (VOs) are valuable tools for studying vascular development, disease, and regenerative medicine. However, controlling endothelial and mural compartments independently remains challenging. Here, we present a streamlined method to generate VOs from induced pluripotent stem cells (iPSCs) via orthogonal activation of the transcription factors (TFs) ETV2 and NKX3.1 using Dox-inducible or modRNA systems. This approach enables efficient co-differentiation of endothelial cells (iECs) and mural cells (iMCs), producing functional 3D VOs in 5 days without ECM embedding. VOs matured further upon ECM exposure, forming larger, structured vessels. Single-cell RNA sequencing revealed vascular heterogeneity, and temporal regulation of TF expression allowed modulation of arterial and angiogenic iEC phenotypes. In vivo, VOs engrafted into immunodeficient mice, formed perfused vasculature, and promoted revascularization in models of hind limb ischemia and pancreatic islet transplantation. These findings establish a rapid and versatile VO platform with broad potential for vascular modeling, disease studies, and regenerative cell therapy.","PeriodicalId":9665,"journal":{"name":"Cell stem cell","volume":"22 1","pages":""},"PeriodicalIF":23.9,"publicationDate":"2025-06-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144278515","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

Multiomic profiling reveals that prostaglandin E2 reverses aged muscle stem cell dysfunction, leading to increased regeneration and strength 多组学分析显示，前列腺素E2逆转衰老肌肉干细胞功能障碍，导致再生和力量增加

IF 23.9 1区医学

Cell stem cell Pub Date : 2025-06-12 DOI: 10.1016/j.stem.2025.05.012

Yu Xin Wang, Adelaida R. Palla, Andrew T.V. Ho, Daniel C.L. Robinson, Meenakshi Ravichandran, Glenn J. Markov, Thach Mai, Chris Still, Akshay Balsubramani, Surag Nair, Colin A. Holbrook, Ann V. Yang, Peggy E. Kraft, Shiqi Su, David M. Burns, Nora D. Yucel, Lei S. Qi, Anshul Kundaje, Helen M. Blau

{"title":"Multiomic profiling reveals that prostaglandin E2 reverses aged muscle stem cell dysfunction, leading to increased regeneration and strength","authors":"Yu Xin Wang, Adelaida R. Palla, Andrew T.V. Ho, Daniel C.L. Robinson, Meenakshi Ravichandran, Glenn J. Markov, Thach Mai, Chris Still, Akshay Balsubramani, Surag Nair, Colin A. Holbrook, Ann V. Yang, Peggy E. Kraft, Shiqi Su, David M. Burns, Nora D. Yucel, Lei S. Qi, Anshul Kundaje, Helen M. Blau","doi":"10.1016/j.stem.2025.05.012","DOIUrl":"https://doi.org/10.1016/j.stem.2025.05.012","url":null,"abstract":"Repair of muscle damage declines with age due to the accumulation of dysfunctional muscle stem cells (MuSCs). Here, we uncover that aged MuSCs have blunted prostaglandin E2 (PGE2)-EP4 receptor signaling, which causes precocious commitment and mitotic catastrophe. Treatment with PGE2 alters chromatin accessibility and overcomes the dysfunctional aged MuSC fate trajectory, increasing viability and triggering cell cycle re-entry. We employ neural network models to learn the complex logic of transcription factors driving the change in accessibility. After PGE2 treatment, we detect increased transcription factor binding at sites with CRE and E-box motifs and reduced binding at sites with AP1 motifs, overcoming the changes that occur with age. We find that short-term exposure of aged MuSCs to PGE2 augments their long-term regenerative capacity upon transplantation. Strikingly, PGE2 injections following myotoxin- or exercise-induced injury overcome the aged niche, leading to enhanced regenerative function of endogenous tissue-resident MuSCs and an increase in strength.","PeriodicalId":9665,"journal":{"name":"Cell stem cell","volume":"22 1","pages":""},"PeriodicalIF":23.9,"publicationDate":"2025-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144269215","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

An organoid co-culture model for probing systemic anti-tumor immunity in lung cancer 探讨肺癌全身抗肿瘤免疫的类器官共培养模型

IF 23.9 1区医学

Cell stem cell Pub Date : 2025-06-12 DOI: 10.1016/j.stem.2025.05.011

Kaiyi Li, Chang Liu, Xizhao Sui, Chao Li, Ting Zhang, Tian Zhao, Dong Zhang, Hainan Wu, Yuhan Liu, Shuai Wang, Yingshun Yang, Baobao Lin, Wenyan Wang, Fan Yang, Xiaofang Chen, Peng Liu

{"title":"An organoid co-culture model for probing systemic anti-tumor immunity in lung cancer","authors":"Kaiyi Li, Chang Liu, Xizhao Sui, Chao Li, Ting Zhang, Tian Zhao, Dong Zhang, Hainan Wu, Yuhan Liu, Shuai Wang, Yingshun Yang, Baobao Lin, Wenyan Wang, Fan Yang, Xiaofang Chen, Peng Liu","doi":"10.1016/j.stem.2025.05.011","DOIUrl":"https://doi.org/10.1016/j.stem.2025.05.011","url":null,"abstract":"Deciphering interactions between tumor micro- and systemic immune macroenvironments is essential for developing more effective cancer diagnosis and therapeutic strategies. Here, we established a gel-liquid interface (GLI) co-culture model of lung cancer organoids (LCOs) and paired peripheral-blood mononuclear cells (PBMCs), featuring enhanced interactions between immune cells and tumor organoids for optimized simulation of in vivo systemic anti-tumor immunity. By constructing a cohort of lung cancer patients, we demonstrated that the responses of GLI models under αPD1 treatment reflected the immunotherapy outcomes of the corresponding patients precisely. Furthermore, we dissected the various tumor immune processes mediated by PBMC-derived T cells within GLI models through functional multi-omics analyses, along with the characterization of circulating tumor-reactive T cells (GNLY+CD44+CD9+) with effector memory-like phenotypes as a potential indicator of immunotherapy efficacy. Our findings indicate that the GLI co-culture model can be used to develop diagnostic strategies for precision immunotherapies, as well as understanding the underlying mechanisms.","PeriodicalId":9665,"journal":{"name":"Cell stem cell","volume":"100 1","pages":""},"PeriodicalIF":23.9,"publicationDate":"2025-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144269214","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

Human airway submucosal gland organoids to study respiratory inflammation and infection 人气道粘膜下腺类器官研究呼吸道炎症和感染

IF 23.9 1区医学

Cell stem cell Pub Date : 2025-06-12 DOI: 10.1016/j.stem.2025.05.013

Lin Lin, Carla Pou Casellas, Antonella F.M. Dost, Harry Begthel, Jeroen Korving, Stieneke van den Brink, Talya Dayton, Matthijs F.M. van Oosterhout, Niels Smakman, Lisa Thomann, Volker Thiel, Johan H. van Es, Hans Clevers

{"title":"Human airway submucosal gland organoids to study respiratory inflammation and infection","authors":"Lin Lin, Carla Pou Casellas, Antonella F.M. Dost, Harry Begthel, Jeroen Korving, Stieneke van den Brink, Talya Dayton, Matthijs F.M. van Oosterhout, Niels Smakman, Lisa Thomann, Volker Thiel, Johan H. van Es, Hans Clevers","doi":"10.1016/j.stem.2025.05.013","DOIUrl":"https://doi.org/10.1016/j.stem.2025.05.013","url":null,"abstract":"The human airway lining consists of two physiologically distinct compartments: the surface airway epithelium (SAE) and the submucosal glands (SMGs). Despite their critical role, the SMGs have remained largely overlooked in airway in vitro modeling of respiratory inflammation and infection. In this study, we leverage long-term cultured organoids derived separately from SAE and SMGs to investigate their unique physiological characteristics. Single-cell RNA sequencing (scRNA-seq) analysis confirms that these organoid models accurately replicate the cellular heterogeneity inherent to each tissue type. Specifically, SMG organoids are enriched in MUC5B-producing mucous cells and also generate alpha-smooth muscle actin (αSMA)-expressing myoepithelial cells. ANPEP/CD13 specifically marks SMG secretory cells. Exposure to cytokines elicits distinct inflammatory transcriptomic responses in SMG secretory cells. Infection assays with human alpha-coronavirus 229E (HCoV-229E) reveal the selective vulnerability of CD13-positive secretory cells, triggering an unfolded protein response. These findings broaden the utility of airway organoids for modeling respiratory (patho-)physiology.","PeriodicalId":9665,"journal":{"name":"Cell stem cell","volume":"19 1","pages":""},"PeriodicalIF":23.9,"publicationDate":"2025-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144269213","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

From genes to geometry: Controlling embryo models by programming genomic activation 从基因到几何：通过编程基因组激活来控制胚胎模型

IF 23.9 1区医学

Cell stem cell Pub Date : 2025-06-05 DOI: 10.1016/j.stem.2025.04.013

Harold M. McNamara, Berna Sozen

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On-demand microglia deliver the therapeutic payload in Alzheimer’s disease 按需小胶质细胞提供治疗阿尔茨海默病的有效载荷

IF 23.9 1区医学

Cell stem cell Pub Date : 2025-06-05 DOI: 10.1016/j.stem.2025.05.003

Jessica M. Thanos, John R. Lukens

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Hallmarks of MSCs: Key quality attributes for pharmacology and clinical use msc的特点：药理学和临床使用的关键质量属性