Cell stem cell最新文献_第10页

Human vascularized macrophage-islet organoids to model immune-mediated pancreatic β cell pyroptosis upon viral infection 用人血管化巨噬细胞-胰岛器官组织模拟病毒感染时免疫介导的胰腺 β 细胞脓毒症

IF 23.9 1区医学

Cell stem cell Pub Date : 2024-09-03 DOI: 10.1016/j.stem.2024.08.007

Liuliu Yang, Yuling Han, Tuo Zhang, Xue Dong, Jian Ge, Aadita Roy, Jiajun Zhu, Tiankun Lu, J. Jeya Vandana, Neranjan de Silva, Catherine C. Robertson, Jenny Z. Xiang, Chendong Pan, Yanjie Sun, Jianwen Que, Todd Evans, Chengyang Liu, Wei Wang, Ali Naji, Stephen C.J. Parker, Shuibing Chen

{"title":"Human vascularized macrophage-islet organoids to model immune-mediated pancreatic β cell pyroptosis upon viral infection","authors":"Liuliu Yang, Yuling Han, Tuo Zhang, Xue Dong, Jian Ge, Aadita Roy, Jiajun Zhu, Tiankun Lu, J. Jeya Vandana, Neranjan de Silva, Catherine C. Robertson, Jenny Z. Xiang, Chendong Pan, Yanjie Sun, Jianwen Que, Todd Evans, Chengyang Liu, Wei Wang, Ali Naji, Stephen C.J. Parker, Shuibing Chen","doi":"10.1016/j.stem.2024.08.007","DOIUrl":"https://doi.org/10.1016/j.stem.2024.08.007","url":null,"abstract":"There is a paucity of human models to study immune-mediated host damage. Here, we utilized the GeoMx spatial multi-omics platform to analyze immune cell changes in COVID-19 pancreatic autopsy samples, revealing an accumulation of proinflammatory macrophages. Single-cell RNA sequencing (scRNA-seq) analysis of human islets exposed to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) or coxsackievirus B4 (CVB4) viruses identified activation of proinflammatory macrophages and β cell pyroptosis. To distinguish viral versus proinflammatory-macrophage-mediated β cell pyroptosis, we developed human pluripotent stem cell (hPSC)-derived vascularized macrophage-islet (VMI) organoids. VMI organoids exhibited enhanced marker expression and function in both β cells and endothelial cells compared with separately cultured cells. Notably, proinflammatory macrophages within VMI organoids induced β cell pyroptosis. Mechanistic investigations highlighted TNFSF12-TNFRSF12A involvement in proinflammatory-macrophage-mediated β cell pyroptosis. This study established hPSC-derived VMI organoids as a valuable tool for studying immune-cell-mediated host damage and uncovered the mechanism of β cell damage during viral exposure.","PeriodicalId":9665,"journal":{"name":"Cell stem cell","volume":"149 1","pages":""},"PeriodicalIF":23.9,"publicationDate":"2024-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142123926","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

Inflammation-induced epigenetic imprinting regulates intestinal stem cells 炎症诱导的表观遗传印记调控肠道干细胞

IF 23.9 1区医学

Cell stem cell Pub Date : 2024-09-03 DOI: 10.1016/j.stem.2024.08.006

Dongchang Zhao, Visweswaran Ravikumar, Tyler J. Leach, Daniel Kraushaar, Emma Lauder, Lu Li, Yaping Sun, Katherine Oravecz-Wilson, Evan T. Keller, Fengju Chen, Laure Maneix, Robert R. Jenq, Robert Britton, Katherine Y. King, Ana E. Santibanez, Chad J. Creighton, Arvind Rao, Pavan Reddy

{"title":"Inflammation-induced epigenetic imprinting regulates intestinal stem cells","authors":"Dongchang Zhao, Visweswaran Ravikumar, Tyler J. Leach, Daniel Kraushaar, Emma Lauder, Lu Li, Yaping Sun, Katherine Oravecz-Wilson, Evan T. Keller, Fengju Chen, Laure Maneix, Robert R. Jenq, Robert Britton, Katherine Y. King, Ana E. Santibanez, Chad J. Creighton, Arvind Rao, Pavan Reddy","doi":"10.1016/j.stem.2024.08.006","DOIUrl":"https://doi.org/10.1016/j.stem.2024.08.006","url":null,"abstract":"It remains unknown whether and how intestinal stem cells (ISCs) adapt to inflammatory exposure and whether the adaptation leaves scars that will affect their subsequent regeneration. We investigated the consequences of inflammation on Lgr5+ ISCs in well-defined clinically relevant models of acute gastrointestinal graft-versus-host disease (GI GVHD). Utilizing single-cell transcriptomics, as well as organoid, metabolic, epigenomic, and in vivo models, we found that Lgr5+ ISCs undergo metabolic changes that lead to the accumulation of succinate, which reprograms their epigenome. These changes reduced the ability of ISCs to differentiate and regenerate ex vivo in serial organoid cultures and also in vivo following serial transplantation. Furthermore, ISCs demonstrated a reduced capacity for in vivo regeneration despite resolution of the initial inflammatory exposure, demonstrating the persistence of the maladaptive impact induced by the inflammatory encounter. Thus, inflammation imprints the epigenome of ISCs in a manner that persists and affects their sensitivity to adapt to future stress or challenges.","PeriodicalId":9665,"journal":{"name":"Cell stem cell","volume":"16 1","pages":""},"PeriodicalIF":23.9,"publicationDate":"2024-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142123911","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

Generation of human region-specific brain organoids with medullary spinal trigeminal nuclei 生成具有延髓脊髓三叉神经核的特定区域人脑器官组织

IF 23.9 1区医学

Cell stem cell Pub Date : 2024-08-28 DOI: 10.1016/j.stem.2024.08.004

引用次数: 0

Context-dependent roles of mitochondrial LONP1 in orchestrating the balance between airway progenitor versus progeny cells 线粒体 LONP1 在协调气道祖细胞与后代细胞之间的平衡中的作用与环境有关

IF 23.9 1区医学

Cell stem cell Pub Date : 2024-08-23 DOI: 10.1016/j.stem.2024.08.001

Le Xu, Chunting Tan, Justinn Barr, Nicole Talaba, Jamie Verheyden, Ji Sun Chin, Samvel Gaboyan, Nikita Kasaraneni, Ruth M. Elgamal, Kyle J. Gaulton, Grace Lin, Kamyar Afshar, Eugene Golts, Angela Meier, Laura E. Crotty Alexander, Zea Borok, Yufeng Shen, Wendy K. Chung, David J. McCulley, Xin Sun

{"title":"Context-dependent roles of mitochondrial LONP1 in orchestrating the balance between airway progenitor versus progeny cells","authors":"Le Xu, Chunting Tan, Justinn Barr, Nicole Talaba, Jamie Verheyden, Ji Sun Chin, Samvel Gaboyan, Nikita Kasaraneni, Ruth M. Elgamal, Kyle J. Gaulton, Grace Lin, Kamyar Afshar, Eugene Golts, Angela Meier, Laura E. Crotty Alexander, Zea Borok, Yufeng Shen, Wendy K. Chung, David J. McCulley, Xin Sun","doi":"10.1016/j.stem.2024.08.001","DOIUrl":"https://doi.org/10.1016/j.stem.2024.08.001","url":null,"abstract":"While all eukaryotic cells are dependent on mitochondria for function, in a complex tissue, which cell type and which cell behavior are more sensitive to mitochondrial deficiency remain unpredictable. Here, we show that in the mouse airway, compromising mitochondrial function by inactivating mitochondrial protease gene Lonp1 led to reduced progenitor proliferation and differentiation during development, apoptosis of terminally differentiated ciliated cells and their replacement by basal progenitors and goblet cells during homeostasis, and failed airway progenitor migration into damaged alveoli following influenza infection. ATF4 and the integrated stress response (ISR) pathway are elevated and responsible for the airway phenotypes. Such context-dependent sensitivities are predicted by the selective expression of Bok, which is required for ISR activation. Reduced LONP1 expression is found in chronic obstructive pulmonary disease (COPD) airways with squamous metaplasia. These findings illustrate a cellular energy landscape whereby compromised mitochondrial function could favor the emergence of pathological cell types.","PeriodicalId":9665,"journal":{"name":"Cell stem cell","volume":"42 1","pages":""},"PeriodicalIF":23.9,"publicationDate":"2024-08-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142043073","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

Mitochondrial serine catabolism safeguards maintenance of the hematopoietic stem cell pool in homeostasis and injury 线粒体丝氨酸分解为维持造血干细胞池的平衡和损伤提供保障

IF 23.9 1区医学

Cell stem cell Pub Date : 2024-08-23 DOI: 10.1016/j.stem.2024.07.009

Changhong Du, Chaonan Liu, Kuan Yu, Shuzhen Zhang, Zeyu Fu, Xinliang Chen, Weinian Liao, Jun Chen, Yimin Zhang, Xinmiao Wang, Mo Chen, Fang Chen, Mingqiang Shen, Cheng Wang, Shilei Chen, Song Wang, Junping Wang

{"title":"Mitochondrial serine catabolism safeguards maintenance of the hematopoietic stem cell pool in homeostasis and injury","authors":"Changhong Du, Chaonan Liu, Kuan Yu, Shuzhen Zhang, Zeyu Fu, Xinliang Chen, Weinian Liao, Jun Chen, Yimin Zhang, Xinmiao Wang, Mo Chen, Fang Chen, Mingqiang Shen, Cheng Wang, Shilei Chen, Song Wang, Junping Wang","doi":"10.1016/j.stem.2024.07.009","DOIUrl":"https://doi.org/10.1016/j.stem.2024.07.009","url":null,"abstract":"Hematopoietic stem cells (HSCs) employ a very unique metabolic pattern to maintain themselves, while the spectrum of their metabolic adaptations remains incompletely understood. Here, we uncover a distinct and heterogeneous serine metabolism within HSCs and identify mouse HSCs as a serine auxotroph whose maintenance relies on exogenous serine and the ensuing mitochondrial serine catabolism driven by the hydroxymethyltransferase 2 (SHMT2)-methylene-tetrahydrofolate dehydrogenase 2 (MTHFD2) axis. Mitochondrial serine catabolism primarily feeds NAD(P)H generation to maintain redox balance and thereby diminishes ferroptosis susceptibility of HSCs. Dietary serine deficiency, or genetic or pharmacological inhibition of the SHMT2-MTHFD2 axis, increases ferroptosis susceptibility of HSCs, leading to impaired maintenance of the HSC pool. Moreover, exogenous serine protects HSCs from irradiation-induced myelosuppressive injury by fueling mitochondrial serine catabolism to mitigate ferroptosis. These findings reframe the canonical view of serine from a nonessential amino acid to an essential niche metabolite for HSC pool maintenance.","PeriodicalId":9665,"journal":{"name":"Cell stem cell","volume":"37 1","pages":""},"PeriodicalIF":23.9,"publicationDate":"2024-08-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142043120","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

Incompatibility in cell adhesion constitutes a barrier to interspecies chimerism 细胞粘附不相容是种间嵌合的障碍

IF 23.9 1区医学

Cell stem cell Pub Date : 2024-08-23 DOI: 10.1016/j.stem.2024.07.010

Emily Ballard, Masahiro Sakurai, Leqian Yu, Lizhong Liu, Seiya Oura, Jia Huang, Jun Wu

引用次数: 0

A primate-specific endogenous retroviral envelope protein sequesters SFRP2 to regulate human cardiomyocyte development 一种灵长类特异性内源性逆转录病毒包膜蛋白能封存 SFRP2，从而调节人类心肌细胞的发育

IF 23.9 1区医学

Cell stem cell Pub Date : 2024-08-14 DOI: 10.1016/j.stem.2024.07.006

{"title":"A primate-specific endogenous retroviral envelope protein sequesters SFRP2 to regulate human cardiomyocyte development","authors":"","doi":"10.1016/j.stem.2024.07.006","DOIUrl":"https://doi.org/10.1016/j.stem.2024.07.006","url":null,"abstract":"Endogenous retroviruses (ERVs) occupy a significant part of the human genome, with some encoding proteins that influence the immune system or regulate cell-cell fusion in early extra-embryonic development. However, whether ERV-derived proteins regulate somatic development is unknown. Here, we report a somatic developmental function for the primate-specific ERVH48-1 (SUPYN/Suppressyn). ERVH48-1 encodes a fragment of a viral envelope that is expressed during early embryonic development. Loss of ERVH48-1 led to impaired mesoderm and cardiomyocyte commitment and diverted cells to an ectoderm-like fate. Mechanistically, ERVH48-1 is localized to sub-cellular membrane compartments through a functional N-terminal signal peptide and binds to the WNT antagonist SFRP2 to promote its polyubiquitination and degradation, thus limiting SFRP2 secretion and blocking repression of WNT/β-catenin signaling. Knockdown of SFRP2 or expression of a chimeric SFRP2 with the ERVH48-1 signal peptide rescued cardiomyocyte differentiation. This study demonstrates how ERVH48-1 modulates WNT/β-catenin signaling and cell type commitment in somatic development.","PeriodicalId":9665,"journal":{"name":"Cell stem cell","volume":"40 1","pages":""},"PeriodicalIF":23.9,"publicationDate":"2024-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141981009","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 amphiregulin expression in intermediate alveolar stem cells drives progressive fibrosis 中间肺泡干细胞中持续表达两性胰岛素会导致渐进性纤维化

IF 23.9 1区医学

Cell stem cell Pub Date : 2024-08-02 DOI: 10.1016/j.stem.2024.07.004

引用次数: 0

Macrophages: A missing key in cardiac tissue engineering for sustained vascularization 巨噬细胞：心脏组织工程中缺失的关键--持续血管化

IF 23.9 1区医学

Cell stem cell Pub Date : 2024-08-01 DOI: 10.1016/j.stem.2024.07.001

引用次数: 0

Setting the stage for embryo segmentation 为胚胎分割创造条件

IF 23.9 1区医学

Cell stem cell Pub Date : 2024-08-01 DOI: 10.1016/j.stem.2024.06.014

引用次数: 0