Cell stem cell最新文献_第10页

Construction of multilayered small intestine-like tissue by reproducing interstitial flow 通过再现间隙流构建多层小肠样组织

IF 23.9 1区医学

Cell stem cell Pub Date : 2024-07-11 DOI: 10.1016/j.stem.2024.06.012

Sayaka Deguchi, Kaori Kosugi, Naoki Takeishi, Yukio Watanabe, Shiho Morimoto, Ryosuke Negoro, Fuki Yokoi, Hiroki Futatsusako, May Nakajima-Koyama, Mio Iwasaki, Takuya Yamamoto, Yoshiya Kawaguchi, Yu-suke Torisawa, Kazuo Takayama

{"title":"Construction of multilayered small intestine-like tissue by reproducing interstitial flow","authors":"Sayaka Deguchi, Kaori Kosugi, Naoki Takeishi, Yukio Watanabe, Shiho Morimoto, Ryosuke Negoro, Fuki Yokoi, Hiroki Futatsusako, May Nakajima-Koyama, Mio Iwasaki, Takuya Yamamoto, Yoshiya Kawaguchi, Yu-suke Torisawa, Kazuo Takayama","doi":"10.1016/j.stem.2024.06.012","DOIUrl":"https://doi.org/10.1016/j.stem.2024.06.012","url":null,"abstract":"Recent advances have made modeling human small intestines in vitro possible, but it remains a challenge to recapitulate fully their structural and functional characteristics. We suspected interstitial flow within the intestine, powered by circulating blood plasma during embryonic organogenesis, to be a vital factor. We aimed to construct an in vivo-like multilayered small intestinal tissue by incorporating interstitial flow into the system and, in turn, developed the micro-small intestine system by differentiating definitive endoderm and mesoderm cells from human pluripotent stem cells simultaneously on a microfluidic device capable of replicating interstitial flow. This approach enhanced cell maturation and led to the development of a three-dimensional small intestine-like tissue with villi-like epithelium and an aligned mesenchymal layer. Our micro-small intestine system not only overcomes the limitations of conventional intestine models but also offers a unique opportunity to gain insights into the detailed mechanisms underlying intestinal tissue development.","PeriodicalId":9665,"journal":{"name":"Cell stem cell","volume":"37 1","pages":""},"PeriodicalIF":23.9,"publicationDate":"2024-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141588765","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

Disruption of TGF-β signaling pathway is required to mediate effective killing of hepatocellular carcinoma by human iPSC-derived NK cells 人 iPSC 衍生 NK 细胞有效杀伤肝细胞癌需要 TGF-β 信号通路的干扰

IF 23.9 1区医学

Cell stem cell Pub Date : 2024-07-09 DOI: 10.1016/j.stem.2024.06.009

Jaya Lakshmi Thangaraj, Michael Coffey, Edith Lopez, Dan S. Kaufman

引用次数: 0

A human pluripotent stem cell-based somitogenesis model using microfluidics 利用微流体技术建立基于人类多能干细胞的体细胞发生模型

IF 23.9 1区医学

Cell stem cell Pub Date : 2024-07-08 DOI: 10.1016/j.stem.2024.06.004

Yue Liu, Yung Su Kim, Xufeng Xue, Yuchuan Miao, Norio Kobayashi, Shiyu Sun, Robin Zhexuan Yan, Qiong Yang, Olivier Pourquié, Jianping Fu

{"title":"A human pluripotent stem cell-based somitogenesis model using microfluidics","authors":"Yue Liu, Yung Su Kim, Xufeng Xue, Yuchuan Miao, Norio Kobayashi, Shiyu Sun, Robin Zhexuan Yan, Qiong Yang, Olivier Pourquié, Jianping Fu","doi":"10.1016/j.stem.2024.06.004","DOIUrl":"https://doi.org/10.1016/j.stem.2024.06.004","url":null,"abstract":"Emerging human pluripotent stem cell (hPSC)-based embryo models are useful for studying human embryogenesis. Particularly, there are hPSC-based somitogenesis models using free-floating culture that recapitulate somite formation. Somitogenesis in vivo involves intricately orchestrated biochemical and biomechanical events. However, none of the current somitogenesis models controls biochemical gradients or biomechanical signals in the culture, limiting their applicability to untangle complex biochemical-biomechanical interactions that drive somitogenesis. Herein, we develop a human somitogenesis model by confining hPSC-derived presomitic mesoderm (PSM) tissues in microfabricated trenches. Exogenous microfluidic morphogen gradients imposed on the PSM tissues cause axial patterning and trigger spontaneous rostral-to-caudal somite formation. A mechanical theory is developed to explain the size dependency between somites and the PSM. The microfluidic somitogenesis model is further exploited to reveal regulatory roles of cellular and tissue biomechanics in somite formation. This study presents a useful microengineered, hPSC-based model for understanding the biochemical and biomechanical events that guide somite formation.","PeriodicalId":9665,"journal":{"name":"Cell stem cell","volume":"16 1","pages":""},"PeriodicalIF":23.9,"publicationDate":"2024-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141561670","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

Genetic ablation of adhesion ligands mitigates rejection of allogeneic cellular immunotherapies 基因消减粘附配体可减轻异体细胞免疫疗法的排斥反应

IF 23.9 1区医学

Cell stem cell Pub Date : 2024-07-08 DOI: 10.1016/j.stem.2024.06.011

引用次数: 0

Nynrin preserves hematopoietic stem cell function by inhibiting the mitochondrial permeability transition pore opening Nynrin 通过抑制线粒体通透性转换孔的开放来保护造血干细胞的功能

IF 23.9 1区医学

Cell stem cell Pub Date : 2024-07-01 DOI: 10.1016/j.stem.2024.06.007

Chengfang Zhou, Mei Kuang, Yin Tao, Jianming Wang, Yu Luo, Yinghao Fu, Zhe Chen, Yuanyuan Liu, Zhigang Li, Weiru Wu, Li Wang, Ying Dou, Junping Wang, Yu Hou

{"title":"Nynrin preserves hematopoietic stem cell function by inhibiting the mitochondrial permeability transition pore opening","authors":"Chengfang Zhou, Mei Kuang, Yin Tao, Jianming Wang, Yu Luo, Yinghao Fu, Zhe Chen, Yuanyuan Liu, Zhigang Li, Weiru Wu, Li Wang, Ying Dou, Junping Wang, Yu Hou","doi":"10.1016/j.stem.2024.06.007","DOIUrl":"https://doi.org/10.1016/j.stem.2024.06.007","url":null,"abstract":"Mitochondria are key regulators of hematopoietic stem cell (HSC) homeostasis. Our research identifies the transcription factor Nynrin as a crucial regulator of HSC maintenance by modulating mitochondrial function. Nynrin is highly expressed in HSCs under both steady-state and stress conditions. The knockout Nynrin diminishes HSC frequency, dormancy, and self-renewal, with increased mitochondrial dysfunction indicated by abnormal mPTP opening, mitochondrial swelling, and elevated ROS levels. These changes reduce HSC radiation tolerance and promote necrosis-like phenotypes. By contrast, Nynrin overexpression in HSCs diminishes irradiation (IR)-induced lethality. The deletion of Nynrin activates Ppif, leading to overexpression of cyclophilin D (CypD) and further mitochondrial dysfunction. Strategies such as Ppif haploinsufficiency or pharmacological inhibition of CypD significantly mitigate these effects, restoring HSC function in Nynrin-deficient mice. This study identifies Nynrin as a critical regulator of mitochondrial function in HSCs, highlighting potential therapeutic targets for preserving stem cell viability during cancer treatment.","PeriodicalId":9665,"journal":{"name":"Cell stem cell","volume":"337 1","pages":""},"PeriodicalIF":23.9,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141489720","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

Cancer stem cell mimicry for immune evasion and therapeutic resistance 模仿癌症干细胞，实现免疫逃避和抗药性

IF 23.9 1区医学

Cell stem cell Pub Date : 2024-06-25 DOI: 10.1016/j.stem.2024.06.003

Phei Er Saw, Qiang Liu, Ping-Pui Wong, Erwei Song

引用次数: 0

Genome-wide CRISPR screen identifies neddylation as a regulator of neuronal aging and AD neurodegeneration 全基因组CRISPR筛选确定neddylation是神经元衰老和AD神经退行性变的调控因子

IF 23.9 1区医学

Cell stem cell Pub Date : 2024-06-24 DOI: 10.1016/j.stem.2024.06.001

Nathalie Saurat, Andrew P. Minotti, Maliha T. Rahman, Trisha Sikder, Chao Zhang, Daniela Cornacchia, Johannes Jungverdorben, Gabriele Ciceri, Doron Betel, Lorenz Studer

{"title":"Genome-wide CRISPR screen identifies neddylation as a regulator of neuronal aging and AD neurodegeneration","authors":"Nathalie Saurat, Andrew P. Minotti, Maliha T. Rahman, Trisha Sikder, Chao Zhang, Daniela Cornacchia, Johannes Jungverdorben, Gabriele Ciceri, Doron Betel, Lorenz Studer","doi":"10.1016/j.stem.2024.06.001","DOIUrl":"https://doi.org/10.1016/j.stem.2024.06.001","url":null,"abstract":"Aging is the biggest risk factor for the development of Alzheimer’s disease (AD). Here, we performed a whole-genome CRISPR screen to identify regulators of neuronal age and show that the neddylation pathway regulates both cellular age and AD neurodegeneration in a human stem cell model. Specifically, we demonstrate that blocking neddylation increased cellular hallmarks of aging and led to an increase in Tau aggregation and phosphorylation in neurons carrying the APPswe/swe mutation. Aged APPswe/swe but not isogenic control neurons also showed a progressive decrease in viability. Selective neuronal loss upon neddylation inhibition was similarly observed in other isogenic AD and in Parkinson’s disease (PD) models, including PSENM146V/M146V cortical and LRRK2G2019S/G2019S midbrain dopamine neurons, respectively. This study indicates that cellular aging can reveal late-onset disease phenotypes, identifies new potential targets to modulate AD progression, and describes a strategy to program age-associated phenotypes into stem cell models of disease.","PeriodicalId":9665,"journal":{"name":"Cell stem cell","volume":"20 1","pages":""},"PeriodicalIF":23.9,"publicationDate":"2024-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141445012","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

Selective advantage of mutant stem cells in human clonal hematopoiesis is associated with attenuated response to inflammation and aging 人类克隆造血中突变干细胞的选择性优势与炎症和衰老反应减弱有关

IF 23.9 1区医学

Cell stem cell Pub Date : 2024-06-24 DOI: 10.1016/j.stem.2024.05.010

Niels Asger Jakobsen, Sven Turkalj, Andy G.X. Zeng, Bilyana Stoilova, Marlen Metzner, Susann Rahmig, Murtaza S. Nagree, Sayyam Shah, Rachel Moore, Batchimeg Usukhbayar, Mirian Angulo Salazar, Grigore-Aristide Gafencu, Alison Kennedy, Simon Newman, Benjamin J.L. Kendrick, Adrian H. Taylor, Rasheed Afinowi-Luitz, Roger Gundle, Bridget Watkins, Kim Wheway, Paresh Vyas

{"title":"Selective advantage of mutant stem cells in human clonal hematopoiesis is associated with attenuated response to inflammation and aging","authors":"Niels Asger Jakobsen, Sven Turkalj, Andy G.X. Zeng, Bilyana Stoilova, Marlen Metzner, Susann Rahmig, Murtaza S. Nagree, Sayyam Shah, Rachel Moore, Batchimeg Usukhbayar, Mirian Angulo Salazar, Grigore-Aristide Gafencu, Alison Kennedy, Simon Newman, Benjamin J.L. Kendrick, Adrian H. Taylor, Rasheed Afinowi-Luitz, Roger Gundle, Bridget Watkins, Kim Wheway, Paresh Vyas","doi":"10.1016/j.stem.2024.05.010","DOIUrl":"https://doi.org/10.1016/j.stem.2024.05.010","url":null,"abstract":"Clonal hematopoiesis (CH) arises when hematopoietic stem cells (HSCs) acquire mutations, most frequently in the DNMT3A and TET2 genes, conferring a competitive advantage through mechanisms that remain unclear. To gain insight into how CH mutations enable gradual clonal expansion, we used single-cell multi-omics with high-fidelity genotyping on human CH bone marrow (BM) samples. Most of the selective advantage of mutant cells occurs within HSCs. DNMT3A- and TET2-mutant clones expand further in early progenitors, while TET2 mutations accelerate myeloid maturation in a dose-dependent manner. Unexpectedly, both mutant and non-mutant HSCs from CH samples are enriched for inflammatory and aging transcriptomic signatures, compared with HSCs from non-CH samples, revealing a non-cell-autonomous effect. However, DNMT3A- and TET2-mutant HSCs have an attenuated inflammatory response relative to wild-type HSCs within the same sample. Our data support a model whereby CH clones are gradually selected because they are resistant to the deleterious impact of inflammation and aging.","PeriodicalId":9665,"journal":{"name":"Cell stem cell","volume":"20 1","pages":""},"PeriodicalIF":23.9,"publicationDate":"2024-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141444980","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

Primitive macrophages enable long-term vascularization of human heart-on-a-chip platforms 原始巨噬细胞实现了人体心脏芯片平台的长期血管化

IF 23.9 1区医学

Cell stem cell Pub Date : 2024-06-21 DOI: 10.1016/j.stem.2024.05.011

Shira Landau, Yimu Zhao, Homaira Hamidzada, Gregory M. Kent, Sargol Okhovatian, Rick Xing Ze Lu, Chuan Liu, Karl T. Wagner, Krisco Cheung, Sarah A. Shawky, Daniel Vosoughi, Erika Leigh Beroncal, Ian Fernandes, Carolyn L. Cummins, Ana C. Andreazza, Gordon M. Keller, Slava Epelman, Milica Radisic

{"title":"Primitive macrophages enable long-term vascularization of human heart-on-a-chip platforms","authors":"Shira Landau, Yimu Zhao, Homaira Hamidzada, Gregory M. Kent, Sargol Okhovatian, Rick Xing Ze Lu, Chuan Liu, Karl T. Wagner, Krisco Cheung, Sarah A. Shawky, Daniel Vosoughi, Erika Leigh Beroncal, Ian Fernandes, Carolyn L. Cummins, Ana C. Andreazza, Gordon M. Keller, Slava Epelman, Milica Radisic","doi":"10.1016/j.stem.2024.05.011","DOIUrl":"https://doi.org/10.1016/j.stem.2024.05.011","url":null,"abstract":"The intricate anatomical structure and high cellular density of the myocardium complicate the bioengineering of perfusable vascular networks within cardiac tissues. In vivo neonatal studies highlight the key role of resident cardiac macrophages in post-injury regeneration and angiogenesis. Here, we integrate human pluripotent stem-cell-derived primitive yolk-sac-like macrophages within vascularized heart-on-chip platforms. Macrophage incorporation profoundly impacted the functionality and perfusability of microvascularized cardiac tissues up to 2 weeks of culture. Macrophages mitigated tissue cytotoxicity and the release of cell-free mitochondrial DNA (mtDNA), while upregulating the secretion of pro-angiogenic, matrix remodeling, and cardioprotective cytokines. Bulk RNA sequencing (RNA-seq) revealed an upregulation of cardiac maturation and angiogenesis genes. Further, single-nuclei RNA sequencing (snRNA-seq) and secretome data suggest that macrophages may prime stromal cells for vascular development by inducing insulin like growth factor binding protein 7 (IGFBP7) and hepatocyte growth factor (HGF) expression. Our results underscore the vital role of primitive macrophages in the long-term vascularization of cardiac tissues, offering insights for therapy and advancing heart-on-a-chip technologies.","PeriodicalId":9665,"journal":{"name":"Cell stem cell","volume":"7 1","pages":""},"PeriodicalIF":23.9,"publicationDate":"2024-06-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141436026","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

Bioengineered human colon organoids with in vivo-like cellular complexity and function 具有类似活体细胞复杂性和功能的生物工程人结肠器官组织

IF 23.9 1区医学

Cell stem cell Pub Date : 2024-06-13 DOI: 10.1016/j.stem.2024.05.007

Olga Mitrofanova, Mikhail Nikolaev, Quan Xu, Nicolas Broguiere, Irineja Cubela, J. Gray Camp, Michael Bscheider, Matthias P. Lutolf

{"title":"Bioengineered human colon organoids with in vivo-like cellular complexity and function","authors":"Olga Mitrofanova, Mikhail Nikolaev, Quan Xu, Nicolas Broguiere, Irineja Cubela, J. Gray Camp, Michael Bscheider, Matthias P. Lutolf","doi":"10.1016/j.stem.2024.05.007","DOIUrl":"https://doi.org/10.1016/j.stem.2024.05.007","url":null,"abstract":"Organoids and organs-on-a-chip have emerged as powerful tools for modeling human gut physiology and disease in vitro. Although physiologically relevant, these systems often lack the environmental milieu, spatial organization, cell type diversity, and maturity necessary for mimicking human intestinal mucosa. To instead generate models closely resembling in vivo tissue, we herein integrated organoid and organ-on-a-chip technology to develop an advanced human organoid model, called “mini-colons.” By employing an asymmetric stimulation with growth factors, we greatly enhanced tissue longevity and replicated in vivo-like diversity and patterning of proliferative and differentiated cell types. Mini-colons contain abundant mucus-producing goblet cells and, signifying mini-colon maturation, single-cell RNA sequencing reveals emerging mature and functional colonocytes. This methodology is expanded to generate microtissues from the small intestine and incorporate additional microenvironmental components. Finally, our bioengineered organoids provide a precise platform to systematically study human gut physiology and pathology, and a reliable preclinical model for drug safety assessment.","PeriodicalId":9665,"journal":{"name":"Cell stem cell","volume":"70 1","pages":""},"PeriodicalIF":23.9,"publicationDate":"2024-06-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141315832","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