Cell stem cell最新文献_第6页

Stripe out for brain evolution: Astrocytes go human 大脑进化：星形胶质细胞走向人类

IF 23.9 1区医学

Cell stem cell Pub Date : 2025-03-06 DOI: 10.1016/j.stem.2025.02.008

Lara López-González, Víctor Borrell

引用次数: 0

Fetal-like reversion in the regenerating intestine is regulated by mesenchymal asporin 在再生肠中，胎儿样的逆转是由间充质间质酶调节的

IF 23.9 1区医学

Cell stem cell Pub Date : 2025-03-06 DOI: 10.1016/j.stem.2025.02.009

Sharif Iqbal, Simon Andersson, Ernesta Nesta, Nalle Pentinmikko, Ashish Kumar, Sawan Kumar Jha, Daniel Borshagovski, Anna Webb, Nadja Gebert, Emma W. Viitala, Alexandra Ritchie, Sandra Scharaw, Emilia Kuuluvainen, Hjalte L. Larsen, Tuure Saarinen, Anne Juuti, Ari Ristimäki, Michael Jeltsch, Alessandro Ori, Markku Varjosalo, Pekka Katajisto

{"title":"Fetal-like reversion in the regenerating intestine is regulated by mesenchymal asporin","authors":"Sharif Iqbal, Simon Andersson, Ernesta Nesta, Nalle Pentinmikko, Ashish Kumar, Sawan Kumar Jha, Daniel Borshagovski, Anna Webb, Nadja Gebert, Emma W. Viitala, Alexandra Ritchie, Sandra Scharaw, Emilia Kuuluvainen, Hjalte L. Larsen, Tuure Saarinen, Anne Juuti, Ari Ristimäki, Michael Jeltsch, Alessandro Ori, Markku Varjosalo, Pekka Katajisto","doi":"10.1016/j.stem.2025.02.009","DOIUrl":"https://doi.org/10.1016/j.stem.2025.02.009","url":null,"abstract":"Mesenchymal cells and the extracellular matrix (ECM) support epithelium during homeostasis and regeneration. However, the role of the mesenchyme in epithelial conversion into a fetal-like regenerative state after damage is not known. We modeled epithelial regeneration by culturing intestinal epithelium on decellularized small intestinal scaffolds (iECM) and identify asporin (Aspn), an ECM-bound proteoglycan, as a critical mediator of epithelial fetal-like reprogramming. After damage, transient increase in Aspn expression by the pericryptal fibroblasts induces epithelial transforming growth factor β (TGF-β)-signaling via CD44 and promotes timely epithelial reprogramming. Temporal control of Aspn is lost in old mice, and after damage, the persistently high level of Aspn stagnates epithelium in the regenerative state. Increase in Wnt signaling can resolve the stagnated regenerative program of the old epithelium, promoting restoration of tissue function. In summary, we establish a platform for modeling epithelial injury responses ex vivo and show that the mesenchymal Aspn-producing niche modulates tissue repair by regulating epithelial fetal-like reprogramming.","PeriodicalId":9665,"journal":{"name":"Cell stem cell","volume":"33 1","pages":""},"PeriodicalIF":23.9,"publicationDate":"2025-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143560861","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}

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Autologous cells, no longer lost in translation 自体细胞，在翻译过程中不再丢失

IF 23.9 1区医学

Cell stem cell Pub Date : 2025-03-06 DOI: 10.1016/j.stem.2025.02.004

Malin Parmar, Anna Falk

引用次数: 0

Overcoming gene dosage barriers in mammalian development: An imprinting balancing act 克服哺乳动物发育中的基因剂量障碍：印迹平衡行为

IF 23.9 1区医学

Cell stem cell Pub Date : 2025-03-06 DOI: 10.1016/j.stem.2025.02.005

Zhengfeng Liu, Marisa S. Bartolomei

引用次数: 0

Coordinated differentiation of human intestinal organoids with functional enteric neurons and vasculature 具有功能性肠神经元和血管的人肠道类器官的协调分化

IF 23.9 1区医学

Cell stem cell Pub Date : 2025-03-04 DOI: 10.1016/j.stem.2025.02.007

Charlie J. Childs, Holly M. Poling, Kevin Chen, Yu-Hwai Tsai, Angeline Wu, Abigail Vallie, Madeline K. Eiken, Sha Huang, Caden W. Sweet, Ryan Schreiner, Zhiwei Xiao, Ryan C. Spencer, Samantha A. Paris, Ansley S. Conchola, Jonathan W. Villanueva, Meghan F. Anderman, Emily M. Holloway, Akaljot Singh, Roman J. Giger, Maxime M. Mahe, Jason R. Spence

{"title":"Coordinated differentiation of human intestinal organoids with functional enteric neurons and vasculature","authors":"Charlie J. Childs, Holly M. Poling, Kevin Chen, Yu-Hwai Tsai, Angeline Wu, Abigail Vallie, Madeline K. Eiken, Sha Huang, Caden W. Sweet, Ryan Schreiner, Zhiwei Xiao, Ryan C. Spencer, Samantha A. Paris, Ansley S. Conchola, Jonathan W. Villanueva, Meghan F. Anderman, Emily M. Holloway, Akaljot Singh, Roman J. Giger, Maxime M. Mahe, Jason R. Spence","doi":"10.1016/j.stem.2025.02.007","DOIUrl":"https://doi.org/10.1016/j.stem.2025.02.007","url":null,"abstract":"Human intestinal organoids (HIOs) derived from human pluripotent stem cells co-differentiate both epithelial and mesenchymal lineages in vitro but lack important cell types such as neurons, endothelial cells, and smooth muscle, which limits translational potential. Here, we demonstrate that the intestinal stem cell niche factor, EPIREGULIN (EREG), enhances HIO differentiation with epithelium, mesenchyme, enteric neuroglial populations, endothelial cells, and organized smooth muscle in a single differentiation, without the need for co-culture. When transplanted into a murine host, HIOs mature and demonstrate enteric nervous system function, undergoing peristaltic-like contractions indicative of a functional neuromuscular unit. HIOs also form functional vasculature, demonstrated in vitro using microfluidic devices and in vivo following transplantation, where HIO endothelial cells anastomose with host vasculature. These complex HIOs represent a transformative tool for translational research in the human gut and can be used to interrogate complex diseases as well as for testing therapeutic interventions with high fidelity to human pathophysiology.","PeriodicalId":9665,"journal":{"name":"Cell stem cell","volume":"85 1","pages":""},"PeriodicalIF":23.9,"publicationDate":"2025-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143538715","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

Inhibition of PRC2 enables self-renewal of blastoid-competent naive pluripotent stem cells from chimpanzee 抑制PRC2可使黑猩猩胚状能幼稚多能干细胞自我更新

IF 23.9 1区医学

Cell stem cell Pub Date : 2025-02-26 DOI: 10.1016/j.stem.2025.02.002

Tao Huang, Arthur Radley, Ayaka Yanagida, Zhili Ren, Francesca Carlisle, Somayyeh Tahajjodi, Dongwan Kim, Paul O’Neill, James Clarke, Madeline A. Lancaster, Zoe Heckhausen, Jingran Zhuo, João Pedro Agostinho de Sousa, Petra Hajkova, Ferdinand von Meyenn, Hiroo Imai, Hiromitsu Nakauchi, Ge Guo, Austin Smith, Hideki Masaki

{"title":"Inhibition of PRC2 enables self-renewal of blastoid-competent naive pluripotent stem cells from chimpanzee","authors":"Tao Huang, Arthur Radley, Ayaka Yanagida, Zhili Ren, Francesca Carlisle, Somayyeh Tahajjodi, Dongwan Kim, Paul O’Neill, James Clarke, Madeline A. Lancaster, Zoe Heckhausen, Jingran Zhuo, João Pedro Agostinho de Sousa, Petra Hajkova, Ferdinand von Meyenn, Hiroo Imai, Hiromitsu Nakauchi, Ge Guo, Austin Smith, Hideki Masaki","doi":"10.1016/j.stem.2025.02.002","DOIUrl":"https://doi.org/10.1016/j.stem.2025.02.002","url":null,"abstract":"Naive pluripotent stem cells (PSCs) are counterparts of early epiblast in the mammalian embryo. Mouse and human naive PSCs differ in self-renewal requirements and extraembryonic lineage potency. Here, we investigated the generation of chimpanzee naive PSCs. Colonies generated by resetting or reprogramming failed to propagate. We discovered that self-renewal is enabled by inhibition of Polycomb repressive complex 2 (PRC2). Expanded cells show global transcriptome proximity to human naive PSCs and embryo pre-implantation epiblast, with shared expression of a subset of pluripotency transcription factors. Chimpanzee naive PSCs can transition to multilineage competence or can differentiate into trophectoderm and hypoblast, forming tri-lineage blastoids. They thus provide a higher primate comparative model for studying pluripotency and early embryogenesis. Genetic deletions confirm that PRC2 mediates growth arrest. Further, inhibition of PRC2 overcomes a roadblock to feeder-free propagation of human naive PSCs. Therefore, excess deposition of chromatin modification H3K27me3 is an unexpected barrier to naive PSC self-renewal.","PeriodicalId":9665,"journal":{"name":"Cell stem cell","volume":"22 1","pages":""},"PeriodicalIF":23.9,"publicationDate":"2025-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143495780","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

Pre-existing stem cell heterogeneity dictates clonal responses to the acquisition of leukemic driver mutations 预先存在的干细胞异质性决定了对白血病驱动突变获得的克隆反应

IF 23.9 1区医学

Cell stem cell Pub Date : 2025-02-25 DOI: 10.1016/j.stem.2025.01.012

Indranil Singh, Daniel Fernandez-Perez, Pedro Sanchez Sanchez, Alejo E. Rodriguez-Fraticelli

{"title":"Pre-existing stem cell heterogeneity dictates clonal responses to the acquisition of leukemic driver mutations","authors":"Indranil Singh, Daniel Fernandez-Perez, Pedro Sanchez Sanchez, Alejo E. Rodriguez-Fraticelli","doi":"10.1016/j.stem.2025.01.012","DOIUrl":"https://doi.org/10.1016/j.stem.2025.01.012","url":null,"abstract":"Cancer cells display wide phenotypic variation even across patients with the same mutations. Differences in the cell of origin provide a potential explanation, but traditional assays lack the resolution to distinguish clonally heterogeneous subsets of stem and progenitor cells. To address this challenge, we developed simultaneous tracking of recombinase activation and clonal kinetics (STRACK), a method to trace clonal dynamics and gene expression before and after the acquisition of cancer mutations. Using mouse models, we studied two leukemic mutations, Dnmt3a-R878H and Npm1c, and found that their effect was highly variable across different stem cell states. Specifically, a subset of differentiation-primed stem cells, which normally becomes outcompeted with time, expands with both mutations. Intriguingly, Npm1c mutations reversed the intrinsic bias of the clone of origin, with differentiation-primed stem cells giving rise to more primitive malignant states. Thus, we highlight the relevance of single-cell lineage tracing to unravel early events in cancer evolution and posit that different cellular histories carry distinct cancer phenotypic potential.","PeriodicalId":9665,"journal":{"name":"Cell stem cell","volume":"15 1","pages":""},"PeriodicalIF":23.9,"publicationDate":"2025-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143486529","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

Interferon-responsive intestinal BEST4/CA7+ cells are targets of bacterial diarrheal toxins 干扰素反应性肠道BEST4/CA7+细胞是细菌性腹泻毒素的靶标

IF 23.9 1区医学

Cell stem cell Pub Date : 2025-02-25 DOI: 10.1016/j.stem.2025.02.003

Daisong Wang, Willem Kasper Spoelstra, Lin Lin, Ninouk Akkerman, Daniel Krueger, Talya Dayton, Jeroen S. van Zon, Sander J. Tans, Johan H. van Es, Hans Clevers

{"title":"Interferon-responsive intestinal BEST4/CA7+ cells are targets of bacterial diarrheal toxins","authors":"Daisong Wang, Willem Kasper Spoelstra, Lin Lin, Ninouk Akkerman, Daniel Krueger, Talya Dayton, Jeroen S. van Zon, Sander J. Tans, Johan H. van Es, Hans Clevers","doi":"10.1016/j.stem.2025.02.003","DOIUrl":"https://doi.org/10.1016/j.stem.2025.02.003","url":null,"abstract":"BEST4/CA7+ cells of the human intestine were recently identified by single-cell RNA sequencing. While their gene expression profile predicts a role in electrolyte balance, BEST4/CA7+ cell function has not been explored experimentally owing to the absence of BEST4/CA7+ cells in mice and the paucity of human in vitro models. Here, we establish a protocol that allows the emergence of BEST4/CA7+ cells in human intestinal organoids. Differentiation of BEST4/CA7+ cells requires activation of Notch signaling and the transcription factor SPIB. BEST4/CA7+ cell numbers strongly increase in response to the cytokine interferon-γ, supporting a role in immunity. Indeed, we demonstrate that BEST4/CA7+ cells generate robust CFTR-mediated fluid efflux when stimulated with bacterial diarrhea-causing toxins and find the norepinephrine-ADRA2A axis as a potential mechanism in blocking BEST4/CA7+ cell-mediated fluid secretion. Our observations identify a central role of BEST4/CA7+ cells in fluid homeostasis in response to bacterial infections.","PeriodicalId":9665,"journal":{"name":"Cell stem cell","volume":"5 1","pages":""},"PeriodicalIF":23.9,"publicationDate":"2025-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143486528","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

Enhanced viability and functional maturity of iPSC-derived islet organoids by collagen-VI-enriched ECM scaffolds 利用富含胶原vi的ECM支架增强ipsc衍生的胰岛类器官的活力和功能成熟度

IF 23.9 1区医学

Cell stem cell Pub Date : 2025-02-24 DOI: 10.1016/j.stem.2025.02.001

Deliang Zhu, Zixin Chen, Kaimin Guo, Qingqiang Xie, Yuxiu Zou, Qizheng Mou, Zhongjun Zhou, Guoxiang Jin

{"title":"Enhanced viability and functional maturity of iPSC-derived islet organoids by collagen-VI-enriched ECM scaffolds","authors":"Deliang Zhu, Zixin Chen, Kaimin Guo, Qingqiang Xie, Yuxiu Zou, Qizheng Mou, Zhongjun Zhou, Guoxiang Jin","doi":"10.1016/j.stem.2025.02.001","DOIUrl":"https://doi.org/10.1016/j.stem.2025.02.001","url":null,"abstract":"Islet organoids derived from pluripotent stem cells offer a promising solution for the shortage of cadaveric donors in diabetes treatment. However, challenges remain in improving their differentiation, viability, functional maturity, and engraftment. Here, we generated improved islet organoids with high viability and functionality by employing extracellular matrix (ECM) hydrogel of decellularized amniotic membrane (dAM). The dAM sheet facilitates islet organoid engraftment and rapidly restores normoglycemia in diabetic mice, accompanied by increased body weight and augmented insulin release in response to glucose. Interestingly, collagen VI (Col VI) was identified as a key component of islet niche, enhancing islet cell viability and biological function. Col-VI-based biomimetic ECM recapitulates the native environment and exhibits superior physiological properties. Importantly, the cellular composition and endocrine function of optimized induced pluripotent stem cell (iPSC)-derived islet organoids are comparable with those of human islets. Our findings offer a valuable platform for future endeavors in organoid-transplantation-based therapy of diabetes.","PeriodicalId":9665,"journal":{"name":"Cell stem cell","volume":"65 1","pages":""},"PeriodicalIF":23.9,"publicationDate":"2025-02-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143477375","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

Systems immunology analysis of human immune organoids identifies host-specific correlates of protection to different influenza vaccines 人类免疫类器官的系统免疫学分析确定了对不同流感疫苗保护的宿主特异性相关因子

IF 23.9 1区医学

Cell stem cell Pub Date : 2025-02-21 DOI: 10.1016/j.stem.2025.01.014

Zachary W. Wagoner, Timothy B. Yates, Jenny E. Hernandez-Davies, Suhas Sureshchandra, Erika M. Joloya, Aarti Jain, Rafael de Assis, Jenna M. Kastenschmidt, Andrew M. Sorn, Mahina Tabassum Mitul, Ian Tamburini, Gurpreet Ahuja, Qiu Zhong, Douglas Trask, Marcus Seldin, D. Huw Davies, Lisa E. Wagar

{"title":"Systems immunology analysis of human immune organoids identifies host-specific correlates of protection to different influenza vaccines","authors":"Zachary W. Wagoner, Timothy B. Yates, Jenny E. Hernandez-Davies, Suhas Sureshchandra, Erika M. Joloya, Aarti Jain, Rafael de Assis, Jenna M. Kastenschmidt, Andrew M. Sorn, Mahina Tabassum Mitul, Ian Tamburini, Gurpreet Ahuja, Qiu Zhong, Douglas Trask, Marcus Seldin, D. Huw Davies, Lisa E. Wagar","doi":"10.1016/j.stem.2025.01.014","DOIUrl":"https://doi.org/10.1016/j.stem.2025.01.014","url":null,"abstract":"Vaccines are an essential tool to significantly reduce pathogen-related morbidity and mortality. However, our ability to rationally design vaccines and identify correlates of protection remains limited. Here, we employed an immune organoid approach to capture human adaptive immune response diversity to influenza vaccines and systematically identify host and antigen features linked to vaccine response variability. Our investigation identified established and unique immune signatures correlated with neutralizing antibody responses across seven different influenza vaccines and antigens. Unexpectedly, heightened ex vivo tissue frequencies of T helper (Th)1 cells emerged as both a predictor and a correlate of neutralizing antibody responses to inactivated influenza vaccines (IIVs). Secondary analysis of human public data confirmed that elevated Th1 signatures are associated with antibody responses following in vivo vaccination. These findings demonstrate the utility of human in vitro models for identifying in vivo correlates of protection and establish a role for Th1 functions in influenza vaccination.","PeriodicalId":9665,"journal":{"name":"Cell stem cell","volume":"22 1","pages":""},"PeriodicalIF":23.9,"publicationDate":"2025-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143463094","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