Stem Cell Reports最新文献_第10页

High resolution multi-scale profiling of embryonic germ cell-like cell derivation reveals pluripotent state transitions in humans. 胚胎生殖细胞样细胞衍生的高分辨率多尺度分析揭示了人类多能状态的转变。

IF 5.1 2区医学

Stem Cell Reports Pub Date : 2026-01-13 Epub Date: 2025-12-18 DOI: 10.1016/j.stemcr.2025.102746

Sarah Stucchi, Lessly P Sepulveda-Rincon, Camille Dion, Gaja Matassa, Alessia Valenti, Cristina Cheroni, Alessandro Vitriolo, Filippo Prazzoli, George Young, Marco Tullio Rigoli, Riccardo Nagni, Martina Ciprietti, Benedetta Muda, Zoe Heckhausen, Petra Hajkova, Nicolò Caporale, Giuseppe Testa, Harry G Leitch

{"title":"High resolution multi-scale profiling of embryonic germ cell-like cell derivation reveals pluripotent state transitions in humans.","authors":"Sarah Stucchi, Lessly P Sepulveda-Rincon, Camille Dion, Gaja Matassa, Alessia Valenti, Cristina Cheroni, Alessandro Vitriolo, Filippo Prazzoli, George Young, Marco Tullio Rigoli, Riccardo Nagni, Martina Ciprietti, Benedetta Muda, Zoe Heckhausen, Petra Hajkova, Nicolò Caporale, Giuseppe Testa, Harry G Leitch","doi":"10.1016/j.stemcr.2025.102746","DOIUrl":"10.1016/j.stemcr.2025.102746","url":null,"abstract":"Primordial germ cells (PGCs) are the embryonic precursors of the gametes. In rodents, PGCs readily form self-renewing embryonic germ cell (EGC) lines in vitro. Although human PGCs undergo a similar conversion during germ cell tumorigenesis, no comparable in vitro system has yet been established in humans. Here we report that hPGC-like cells (hPGCLCs) undergo conversion to human EGC-like cells (hEGCLCs) using the inductive signals previously identified in mice. This feeder-free culture system allows efficient derivation of hEGCLCs that are transcriptionally similar to human induced pluripotent stem cells and can give rise to hPGCLCs once more demonstrating the interconvertibility of pluripotent states. This is also evident at the chromatin level, as the initial DNA demethylation that occurs in hPGCLCs is reversed in hEGCLCs. This new in vitro model provides a highly tractable system to study human pluripotent and early developmental transitions, including those driving germ cell tumorigenesis and epigenetic inheritance.","PeriodicalId":21885,"journal":{"name":"Stem Cell Reports","volume":" ","pages":"102746"},"PeriodicalIF":5.1,"publicationDate":"2026-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12925952/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145794820","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Aβ plaques induce local pre-synaptic toxicity in human iPSC-derived neuron xenografts. Aβ斑块诱导人类ipsc来源的神经元异种移植物的局部突触前毒性。

IF 5.1 2区医学

Stem Cell Reports Pub Date : 2026-01-13 Epub Date: 2026-01-02 DOI: 10.1016/j.stemcr.2025.102754

Jacqueline Fréderique Maria van Vierbergen, Carles Calatayud, Sriram Balusu, Nicolò Carrano, Nicolas Peredo, Katlijn Vints, Sandra Fernández Gallego, Katrien Horré, Bart De Strooper, Patrik Verstreken

{"title":"Aβ plaques induce local pre-synaptic toxicity in human iPSC-derived neuron xenografts.","authors":"Jacqueline Fréderique Maria van Vierbergen, Carles Calatayud, Sriram Balusu, Nicolò Carrano, Nicolas Peredo, Katlijn Vints, Sandra Fernández Gallego, Katrien Horré, Bart De Strooper, Patrik Verstreken","doi":"10.1016/j.stemcr.2025.102754","DOIUrl":"10.1016/j.stemcr.2025.102754","url":null,"abstract":"Xenotransplantation enables the interrogation of human neuron-specific vulnerabilities to Alzheimer's pathology within a physiologically relevant in vivo context. While amyloid-beta (Aβ) is known to disrupt synaptic integrity, it remains uncertain whether the synaptotoxicity observed in vitro accurately models the disease. Here, we establish a xenotransplantation paradigm in which human neurons integrate into the brains of amyloid precursor protein (APP) transgenic mice that develop amyloid plaques. Using a genetically encoded pre-synaptic reporter, we label human pre-synapses post engraftment to assess early-stage pathology. We demonstrate that extracellular Aβ plaques induce localized synaptic damage in human neurons, characterized by local pre-synaptic loss and the formation of dystrophic neurites. Notably, this pathology is restricted to the plaque microenvironment and does not result in widespread pre-synaptic degeneration. Our findings establish this human-mouse chimera model as a platform for dissecting Aβ-induced synaptic pathology and reveal that extracellular Aβ exerts compartmentalized yet impactful toxicity on human pre-synapses.","PeriodicalId":21885,"journal":{"name":"Stem Cell Reports","volume":" ","pages":"102754"},"PeriodicalIF":5.1,"publicationDate":"2026-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12925968/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145896867","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Genetic screening of long non-coding RNAs in human embryonic stem cells reveals novel regulators of pluripotency. 人类胚胎干细胞中长链非编码rna的遗传筛选揭示了多能性的新调控因子。

IF 5.1 2区医学

Stem Cell Reports Pub Date : 2026-01-13 Epub Date: 2025-12-18 DOI: 10.1016/j.stemcr.2025.102743

Assa Sherman, Nissim Benvenisty

{"title":"Genetic screening of long non-coding RNAs in human embryonic stem cells reveals novel regulators of pluripotency.","authors":"Assa Sherman, Nissim Benvenisty","doi":"10.1016/j.stemcr.2025.102743","DOIUrl":"10.1016/j.stemcr.2025.102743","url":null,"abstract":"The human genome encodes thousands of long non-coding RNAs (lncRNAs), transcripts of over 200 nucleotides that lack protein-coding potential. lncRNAs are emerging as key players in diverse cellular processes, particularly in tissue-specific contexts, yet their functionality remained poorly understood. Here, we performed a CRISPR interference (CRISPRi) screen in human embryonic stem cells (hESCs), identifying over 100 essential and about 150 growth-restricting lncRNAs. We show that growth-modifying lncRNAs display distinctive properties, including unique expression signatures, genomic structure, evolutionary conservation, chromosomal distribution, and potential involvement in teratoma formation. Notably, we uncovered two primate-conserved, uncharacterized, essential lncRNAs that regulate neighboring pluripotency transcription factors: lncOCT4, which positively regulates OCT4 and induces p53-mediated apoptosis upon knockdown, and lncVRTN, which acts as a putative negative regulator of VRTN, affecting cell fate determination. These findings shed light on the contribution of lncRNAs to the human-specific pluripotency network and provide insights into lncRNA-mediated regulation of hESC growth and differentiation.","PeriodicalId":21885,"journal":{"name":"Stem Cell Reports","volume":" ","pages":"102743"},"PeriodicalIF":5.1,"publicationDate":"2026-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12925960/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145794885","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Transitioning from human primordial germ cells to embryonic germ cells. 人类原始生殖细胞向胚胎生殖细胞的过渡。

IF 5.1 2区医学

Stem Cell Reports Pub Date : 2026-01-13 Epub Date: 2025-12-26 DOI: 10.1016/j.stemcr.2025.102749

Kenyu Iwatsuki, Yasuhiro Takashima

引用次数: 0

Derivation of embryonic stem cells from cloned blastocysts using improved somatic cell nuclear transfer in common marmosets. 利用改进的体细胞核移植从克隆囊胚中提取胚胎干细胞的研究。

IF 5.1 2区医学

Stem Cell Reports Pub Date : 2025-12-09 Epub Date: 2025-11-13 DOI: 10.1016/j.stemcr.2025.102710

Shogo Matoba, Yoko Kurotaki, Satoshi Funaya, Yuko Yamada, Narumi Ogonuki, Haruka Shinohara, Masafumi Yamamoto, Nao Yoneda, Takaya Homma, Yuichiro Higuchi, Erika Sasaki, Atsuo Ogura

{"title":"Derivation of embryonic stem cells from cloned blastocysts using improved somatic cell nuclear transfer in common marmosets.","authors":"Shogo Matoba, Yoko Kurotaki, Satoshi Funaya, Yuko Yamada, Narumi Ogonuki, Haruka Shinohara, Masafumi Yamamoto, Nao Yoneda, Takaya Homma, Yuichiro Higuchi, Erika Sasaki, Atsuo Ogura","doi":"10.1016/j.stemcr.2025.102710","DOIUrl":"10.1016/j.stemcr.2025.102710","url":null,"abstract":"The common marmoset (Callithrix jacchus) is a genetically modifiable non-human primate increasingly used in biomedical research. Here, we established a method for deriving embryonic stem cells (ESCs) from blastocysts generated by somatic cell nuclear transfer (SCNT) in the marmoset. Injection of histone demethylase Kdm4d mRNA enabled efficient reprogramming of somatic nuclei, allowing blastocyst formation in 14.5% from fibroblasts. Combining this method with a G9a/EHMT2 histone methyltransferase inhibitor improved blastocyst quality and allowed derivation of nuclear transfer ESCs (ntESCs), including wild-type and GFP-transgenic lines. These ntESCs exhibited normal karyotypes and pluripotency. Nuclear and mitochondrial DNA analyses confirmed their nuclear donor origin and cytoplasmic inheritance from recipient oocytes. Transcriptome analysis identified abnormally expressed genes in ntESCs present in a line-dependent and independent manner, suggesting partial reprogramming resistance. Our study establishes a marmoset SCNT method enabling derivation of ntESCs and provides a new platform for preserving and engineering marmoset genetic resources.","PeriodicalId":21885,"journal":{"name":"Stem Cell Reports","volume":" ","pages":"102710"},"PeriodicalIF":5.1,"publicationDate":"2025-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12744851/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145522901","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Autophagy is dispensable in germline stem cells but is required in the cap cells for their maintenance in the Drosophila ovarian niche. 自噬在种系干细胞中是可有可无的，但在果蝇卵巢生态位中，帽细胞的维持是必需的。

IF 5.1 2区医学

Stem Cell Reports Pub Date : 2025-12-09 Epub Date: 2025-11-13 DOI: 10.1016/j.stemcr.2025.102712

Kiran Suhas Nilangekar, Bhupendra V Shravage

引用次数: 0

Advances and challenges in modeling Charcot-Marie-Tooth type 2A using iPSC-derived models. 利用ipsc衍生模型对Charcot-Marie-Tooth 2A型进行建模的进展和挑战。

IF 5.1 2区医学

Stem Cell Reports Pub Date : 2025-12-09 Epub Date: 2025-11-13 DOI: 10.1016/j.stemcr.2025.102711

Mafalda Rizzuti, Elisa Pagliari, Martina D'Agostino, Linda Ottoboni, Valeria Parente, Giacomo Pietro Comi, Stefania Corti, Federica Rizzo, Elena Abati

引用次数: 0

Dissecting Oct4 enhancer function in pluripotent stem cells and mouse embryogenesis. 解剖Oct4增强子在多能干细胞和小鼠胚胎发生中的功能。

IF 5.1 2区医学

Stem Cell Reports Pub Date : 2025-12-09 Epub Date: 2025-11-06 DOI: 10.1016/j.stemcr.2025.102706

Daniel A Schmitz, Daiji Okamura, Masahiro Sakurai, Yi Ding, Seiya Oura, Emily Ballard, Yulei Wei, Leqian Yu, Yingying Hu, Jun Wu

引用次数: 0

Aging-dependent reduction of KAT7/HBO1 activity impairs imMKCL-based platelet production by promoting immune properties. KAT7/HBO1活性的衰老依赖性降低通过促进免疫特性损害基于immkcl的血小板生成。

IF 5.1 2区医学

Stem Cell Reports Pub Date : 2025-12-09 Epub Date: 2025-11-13 DOI: 10.1016/j.stemcr.2025.102714

Wei-Yin Qiu, Sou Nakamura, Sudip Kumar Paul, Takuya Yamamoto, Naoya Takayama, Naoshi Sugimoto, Si Jing Chen, Koji Eto

{"title":"Aging-dependent reduction of KAT7/HBO1 activity impairs imMKCL-based platelet production by promoting immune properties.","authors":"Wei-Yin Qiu, Sou Nakamura, Sudip Kumar Paul, Takuya Yamamoto, Naoya Takayama, Naoshi Sugimoto, Si Jing Chen, Koji Eto","doi":"10.1016/j.stemcr.2025.102714","DOIUrl":"10.1016/j.stemcr.2025.102714","url":null,"abstract":"The master cell bank (MCB) system is essential for regenerative cell therapy. We have developed induced pluripotent stem cell (iPSC)-based immortalized megakaryocyte progenitor cell lines (imMKCLs) as an MCB for iPSC-derived platelet (iPSC-PLT) transfusion. However, imMKCLs exhibit both thrombopoietic and immune-skewed properties, with enhanced immune activity impairing platelet production. The link between immune properties and thrombopoietic efficiency remains unclear. Here, we demonstrate that proliferating imMKCLs in G1 and G2/M interphases contribute to platelet generation, while lysine acetyltransferase 7 (KAT7) suppresses immune-biased dominancy to maintain these interphases. KAT7 inhibition with WM3835 increases G0 cells, mimicking imMKCL aging, and induces cGAS-STING activation, chromatin instability, and the secretion of tumor necrosis factor (TNF)-α, interferon (IFN)-β, and other pro-inflammatory cytokines. Additionally, TNF-α treatment recapitulates the transition to G0 seen with KAT7 loss. These findings identify KAT7 as a key regulator of imMKCL proliferation by preventing immune-skewed properties, highlighting its potential as a quality control marker in iPSC-PLT manufacturing.","PeriodicalId":21885,"journal":{"name":"Stem Cell Reports","volume":" ","pages":"102714"},"PeriodicalIF":5.1,"publicationDate":"2025-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12744839/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145522848","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Gene expression profiling reveals enhanced nutrient and drug metabolism and maturation of hiPSC-derived intestine-on-chip relative to organoids and Transwells. 基因表达谱显示，相对于类器官和Transwells， hipsc衍生的芯片上肠道的营养和药物代谢和成熟增强。

IF 5.1 2区医学

Stem Cell Reports Pub Date : 2025-12-09 Epub Date: 2025-11-13 DOI: 10.1016/j.stemcr.2025.102715

Renée Moerkens, Joram Mooiweer, Eline Smits, Marijn Berg, Aarón D Ramírez-Sánchez, Rutger Modderman, Jens Puschhof, Cayetano Pleguezuelos-Manzano, Robert J Barrett, Cisca Wijmenga, Iris H Jonkers, Sebo Withoff

{"title":"Gene expression profiling reveals enhanced nutrient and drug metabolism and maturation of hiPSC-derived intestine-on-chip relative to organoids and Transwells.","authors":"Renée Moerkens, Joram Mooiweer, Eline Smits, Marijn Berg, Aarón D Ramírez-Sánchez, Rutger Modderman, Jens Puschhof, Cayetano Pleguezuelos-Manzano, Robert J Barrett, Cisca Wijmenga, Iris H Jonkers, Sebo Withoff","doi":"10.1016/j.stemcr.2025.102715","DOIUrl":"10.1016/j.stemcr.2025.102715","url":null,"abstract":"The human intestinal epithelial barrier is shaped by biological and biomechanical cues, including growth factor gradients and fluid flow. While these factors are known to affect adult stem cell (ASC)-derived intestinal epithelial cells in vitro, their impact on human induced pluripotent stem cell (hiPSC)-derived cells is largely unexplored. Here, we compare the cellular composition and gene expression profiles of hiPSC-derived intestinal epithelial cells exposed to various medium compositions and cultured as organoids, in Transwell and microfluidic intestine-on-chip systems. Modulating key signaling pathways (WNT, NOTCH, bone morphogenetic protein [BMP], and mitogen-activated protein kinase [MAPK]) influenced the presence of dividing, absorptive, and secretory epithelial lineages. Upon differentiation, intestinal epithelial cells expressed genes encoding digestive enzymes, nutrient transporters, and drug-metabolizing enzymes. Notably, these pathways were most enhanced in the intestine-on-chip system, along with an expression profile that suggests a more mature state. These findings highlight the potential of hiPSC-derived intestinal cells to model important intestinal functions and guide the selection of optimal culture conditions for specific applications.","PeriodicalId":21885,"journal":{"name":"Stem Cell Reports","volume":" ","pages":"102715"},"PeriodicalIF":5.1,"publicationDate":"2025-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12744852/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145522868","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0