Cell stem cell最新文献_第9页

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

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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

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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

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Mini-colons predict drug toxicity in vitro 小圆锥体可预测药物的体外毒性

IF 23.9 1区医学

Cell stem cell Pub Date : 2024-08-01 DOI: 10.1016/j.stem.2024.06.013

引用次数: 0

Engineered vascular grafts lend unique insight to pathophysiology of aortic aneurysms 工程血管移植物为了解主动脉瘤的病理生理学提供了独特视角

IF 23.9 1区医学

Cell stem cell Pub Date : 2024-08-01 DOI: 10.1016/j.stem.2024.07.002

引用次数: 0

Acetyl-CoA metabolism maintains histone acetylation for syncytialization of human placental trophoblast stem cells 乙酰-CoA 代谢维持组蛋白乙酰化，促进人胎盘滋养层干细胞的合胞化

IF 23.9 1区医学

Cell stem cell Pub Date : 2024-07-30 DOI: 10.1016/j.stem.2024.07.003

{"title":"Acetyl-CoA metabolism maintains histone acetylation for syncytialization of human placental trophoblast stem cells","authors":"","doi":"10.1016/j.stem.2024.07.003","DOIUrl":"https://doi.org/10.1016/j.stem.2024.07.003","url":null,"abstract":"During pregnancy, placental-fetal nutrient allocation is crucial for fetal and maternal health. However, the regulatory mechanisms for nutrient metabolism and allocation in placental trophoblasts have remained unclear. Here, we used human first-trimester placenta samples and human trophoblast stem cells (hTSCs) to discover that glucose metabolism is highly active in hTSCs and cytotrophoblasts, but during syncytialization, it decreases to basal levels, remaining necessary for fueling acetyl-CoA and differentiation potential. Acetate supplementation could rescue syncytiotrophoblast fusion from glycolysis deficiency by replenishing acetyl-CoA and maintaining histone acetylation, thus rescuing the activation of syncytialization genes. Even brief glycolysis deficiency could permanently inhibit differentiation potential and promote inflammation, which could also be permanently rescued by brief acetate supplementation in vivo. These results suggest that hTSCs retain only basal glycolytic acetyl-CoA metabolism during syncytialization to regulate cell fates via nutrient-responsive histone acetylation, with implications for our understanding of the balance between placental and fetal nutrition.","PeriodicalId":9665,"journal":{"name":"Cell stem cell","volume":"19 1","pages":""},"PeriodicalIF":23.9,"publicationDate":"2024-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141794971","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