Stem Cell Reports最新文献_第5页

Modeling glioma intratumoral heterogeneity with primary human neural stem and progenitor cells. 用原代人神经干细胞和祖细胞模拟胶质瘤瘤内异质性。

IF 5.1 2区医学

Stem Cell Reports Pub Date : 2025-09-09 Epub Date: 2025-07-31 DOI: 10.1016/j.stemcr.2025.102597

Daniel Dan Liu, Daniel Gao, Nicole L Womack-Gambrel, Anna E Eastman, Benjamin F Ohene-Gambill, Irving L Weissman

{"title":"Modeling glioma intratumoral heterogeneity with primary human neural stem and progenitor cells.","authors":"Daniel Dan Liu, Daniel Gao, Nicole L Womack-Gambrel, Anna E Eastman, Benjamin F Ohene-Gambill, Irving L Weissman","doi":"10.1016/j.stemcr.2025.102597","DOIUrl":"10.1016/j.stemcr.2025.102597","url":null,"abstract":"Gliomas are notorious for their intratumoral heterogeneity, which drives therapy resistance. Glioma tumor cells mimic a neural stem cell (NSC) hierarchy reminiscent of normal brain development. How intratumoral heterogeneity is shaped by cell-of-origin and various driver mutations is not fully understood. We develop a model of glioma initiation using neural stem and progenitor cells (NSPCs) purified from midgestational human brain tissue, including tripotent NSCs, bipotent glial progenitor cells (GPCs), and unipotent oligodendrocyte progenitor cells (OPCs). We transduced these isogenic lines with defined combinations of oncogenic drivers (TP53, NF1, CDK4, EGFR, and PDGFRA) and transplanted them into mice. We find that OPC-derived tumors harbored a higher proportion of differentiated oligodendrocyte-like cells, reminiscent of low-grade oligodendrogliomas. CDK4 drove a neuron-like subtype, while EGFR drove a GPC-like subtype. Our platform is highly adaptable and allows for modular and systematic interrogation of how cell-of-origin and specific driver mutations shape the tumor landscape.","PeriodicalId":21885,"journal":{"name":"Stem Cell Reports","volume":" ","pages":"102597"},"PeriodicalIF":5.1,"publicationDate":"2025-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12447335/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144765512","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

Proteomics-based receptor-ligand matching enhances differentiation maturity of human-stem-cell-derived neurons. 基于蛋白质组学的受体配体匹配促进人类干细胞来源的神经元分化成熟。

IF 5.1 2区医学

Stem Cell Reports Pub Date : 2025-09-09 Epub Date: 2025-08-21 DOI: 10.1016/j.stemcr.2025.102604

Dimitar Dimitrov, Yi Lien, Tetsuya Hori, Yukiko Goda, Christian Rosenmund, Zacharie Taoufiq

{"title":"Proteomics-based receptor-ligand matching enhances differentiation maturity of human-stem-cell-derived neurons.","authors":"Dimitar Dimitrov, Yi Lien, Tetsuya Hori, Yukiko Goda, Christian Rosenmund, Zacharie Taoufiq","doi":"10.1016/j.stemcr.2025.102604","DOIUrl":"10.1016/j.stemcr.2025.102604","url":null,"abstract":"Human-induced pluripotent stem cell (hiPSC) technology enables generation of various cell types, offering significant potential for regenerative medicine and personalized disease modeling. However, optimizing the functional maturity of differentiated cells is crucial for improving their reliability in research. Here, we introduce a deep-proteomics-based \"receptor-ligand matching\" (RLM) strategy to inventory surface receptors on differentiated cells and adjust the culture conditions accordingly. Focusing on an NGN2-induced neuron (iN) model, which rapidly produces glutamatergic neurons but exhibits modest synaptic activity, we identified 3,934 iN membrane proteins, including dozens of growth factor receptors and, notably, the complete GDNF receptor family (GFRA1, GFRA2, and GFRA3) previously undetected. Supplementing culture media with selected ligands enhanced neuronal health, neurite density, and synaptogenesis. Electrophysiology measurements confirmed greater functional synaptic maturity and responsiveness in optimized iNs compared to conventionally generated iNs. The RLM strategy offers a versatile approach to enhance the health and functionality of potentially any hiPSC-derived cell type.","PeriodicalId":21885,"journal":{"name":"Stem Cell Reports","volume":" ","pages":"102604"},"PeriodicalIF":5.1,"publicationDate":"2025-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12447311/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144969639","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

Perturbing neural stem cell fate in glioblastoma heterogeneity and beyond. 神经干细胞命运在胶质母细胞瘤异质性及其他方面的干扰。

IF 5.1 2区医学

Stem Cell Reports Pub Date : 2025-09-09 DOI: 10.1016/j.stemcr.2025.102633

Ethan W Hollingsworth, Jaime Imitola

引用次数: 0

The rise of neural stem cells: From development to disease. 神经干细胞的兴起：从发育到疾病。

IF 5.1 2区医学

Stem Cell Reports Pub Date : 2025-09-09 DOI: 10.1016/j.stemcr.2025.102638

Fiona Doetsch, Rebecca Matsas

引用次数: 0

Trophoblast stem cell derivation from naive and primed hPSC enables ELF5 functional analysis. 从原始和引物的hPSC衍生的滋养细胞干细胞使ELF5功能分析成为可能。

IF 5.1 2区医学

Stem Cell Reports Pub Date : 2025-09-03 DOI: 10.1016/j.stemcr.2025.102637

Joonas Sokka, Ella Lapinsuo, Jouni Kvist, Sami Jalil, Masahito Yoshihara, Jere Weltner, Fredrik Lanner, Juha Kere, Diego Balboa, Timo Otonkoski, Ras Trokovic

{"title":"Trophoblast stem cell derivation from naive and primed hPSC enables ELF5 functional analysis.","authors":"Joonas Sokka, Ella Lapinsuo, Jouni Kvist, Sami Jalil, Masahito Yoshihara, Jere Weltner, Fredrik Lanner, Juha Kere, Diego Balboa, Timo Otonkoski, Ras Trokovic","doi":"10.1016/j.stemcr.2025.102637","DOIUrl":"https://doi.org/10.1016/j.stemcr.2025.102637","url":null,"abstract":"Human pluripotent stem cells (hPSCs) are valuable tools for studying placental biology, yet their differentiation into bona fide trophoblast stem cells (TSCs) remains challenging. In this study, we established and thoroughly compared naive and primed-derived TSC-like cells with primary human TSCs derived from pre-implantation blastocyst and first-trimester placenta. Comprehensive analyses confirmed expression of trophoblast lineage-specific genes and typical placental features. Detailed transcriptional analyses revealed that naive-derived TSC-like cells resembled embryo and placenta-derived cell lines and differentiated faster and more directly into TSC than primed-derived cells. We used these TSC-like models to study the role of ELF5, a transcription factor indispensable for maintenance and differentiation in mouse TSC. In contrast to the mouse, knockout and knockdown experiments revealed that ELF5 is dispensable for human TSC-like cells self-renewal and differentiation. Our study provides valuable transcriptional data and highlights the utility of hPSC-derived TSC-like cells for modeling the placenta and studying gene function.","PeriodicalId":21885,"journal":{"name":"Stem Cell Reports","volume":" ","pages":"102637"},"PeriodicalIF":5.1,"publicationDate":"2025-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145055909","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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

Single-cell glycome and transcriptome profiling uncovers the glycan signature of each cell subpopulation of human iPSC-derived neurons. 单细胞聚糖和转录组分析揭示了人类ipsc衍生神经元的每个细胞亚群的聚糖特征。

IF 5.1 2区医学

Stem Cell Reports Pub Date : 2025-08-29 DOI: 10.1016/j.stemcr.2025.102631

Haruki Odaka, Hiroaki Tateno

{"title":"Single-cell glycome and transcriptome profiling uncovers the glycan signature of each cell subpopulation of human iPSC-derived neurons.","authors":"Haruki Odaka, Hiroaki Tateno","doi":"10.1016/j.stemcr.2025.102631","DOIUrl":"https://doi.org/10.1016/j.stemcr.2025.102631","url":null,"abstract":"Human induced pluripotent stem cell (iPSC)-derived neurons are often heterogeneous, posing challenges for disease modeling and cell therapy. We previously developed single-cell glycan and RNA sequencing (scGR-seq) to analyze the glycome and transcriptome simultaneously. Here, we applied scGR-seq to examine heterogeneous populations of human iPSC-derived neurons. We identified four subpopulations: mature neurons, immature neurons, undifferentiated neural progenitor cells (undiffNPCs), and mesenchymal cells (MCs). Lectin-binding patterns indicated high α1,3-fucose expression in undiffNPCs. MCs exhibited strong binding of a poly-LacNAc-recognizing lectin (rLSLN) and high expression of B3GNT2, a poly-LacNAc synthetic enzyme. Pseudotime analysis revealed that a subpopulation of NPCs acquired mesenchymal features and differentiated into MCs. Immunocytochemistry confirmed the specific detection of undiffNPCs and MCs using anti-Lewis X (α1,3-fucosylated glycan) antibodies and rLSLN. Beyond identifying cell heterogeneity, scGR-seq enables the discovery of glycan markers and detection probes for iPSC-derived cells, aiding in their further cell processing and manipulation.","PeriodicalId":21885,"journal":{"name":"Stem Cell Reports","volume":" ","pages":"102631"},"PeriodicalIF":5.1,"publicationDate":"2025-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145006583","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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

XPRESSO: Rapid genetic engineering of human pluripotent stem cells for durable overexpression using a modular anti-silencing vector. XPRESSO：使用模块化抗沉默载体对人类多能干细胞进行持久过表达的快速基因工程。

IF 5.1 2区医学

Stem Cell Reports Pub Date : 2025-08-19 DOI: 10.1016/j.stemcr.2025.102603

Yehuda Wexler, Harel Grinstein, Irit Huber, Shany Glatstein, Matteo Ghiringhelli, Oded Edri, Michal Landesberg, Daniel Shiff, Gil Arbel, Idan Rosh, Ashwani Choudhary, Shani Stern, Lior Gepstein

{"title":"XPRESSO: Rapid genetic engineering of human pluripotent stem cells for durable overexpression using a modular anti-silencing vector.","authors":"Yehuda Wexler, Harel Grinstein, Irit Huber, Shany Glatstein, Matteo Ghiringhelli, Oded Edri, Michal Landesberg, Daniel Shiff, Gil Arbel, Idan Rosh, Ashwani Choudhary, Shani Stern, Lior Gepstein","doi":"10.1016/j.stemcr.2025.102603","DOIUrl":"https://doi.org/10.1016/j.stemcr.2025.102603","url":null,"abstract":"Ectopic expression of proteins in human pluripotent stem cells (hPSCs) is highly desirable as a research tool and important for clinical translation. However, genetically engineering hPSCs for long-term overexpression of proteins remains inefficient, labor-intensive, and plagued by epigenetic silencing, necessitating dedication of significant resources, and entailing laborious workflows. To address these limitations, we report the development of XPRESSO (expedited persistent and robust engineering of stem cells with sleeping beauty for overexpression), a modular \"anti-silencing\" transposon vector, which we have combined with a highly efficient and accessible methodology for the rapid generation of genetically modified hPSC lines in a gene-independent manner. Using this method, we successfully generated dozens of stable hPSC lines with robust and continuous functional expression of optogenetic proteins, Cas9, shRNA, and a calcium indicator in both undifferentiated and differentiated (cardiomyocyte and neuronal) cells.","PeriodicalId":21885,"journal":{"name":"Stem Cell Reports","volume":" ","pages":"102603"},"PeriodicalIF":5.1,"publicationDate":"2025-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144969687","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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 normal stem cell function and transmission of myelodysplastic syndrome by self-renewal of committed myeloid lineage cells. 骨髓系细胞自我更新对正常干细胞功能的破坏和骨髓增生异常综合征的传递。

IF 5.1 2区医学

Stem Cell Reports Pub Date : 2025-08-12 Epub Date: 2025-07-03 DOI: 10.1016/j.stemcr.2025.102571

Yang Jo Chung, Ryan Bertoli, Dengchao Cao, Robert L Walker, Yuelin Jack Zhu, Paul Meltzer, Peter D Aplan

{"title":"Disruption of normal stem cell function and transmission of myelodysplastic syndrome by self-renewal of committed myeloid lineage cells.","authors":"Yang Jo Chung, Ryan Bertoli, Dengchao Cao, Robert L Walker, Yuelin Jack Zhu, Paul Meltzer, Peter D Aplan","doi":"10.1016/j.stemcr.2025.102571","DOIUrl":"10.1016/j.stemcr.2025.102571","url":null,"abstract":"The ineffective hematopoiesis of myelodysplastic syndrome (MDS) suggests that hematopoietic stem and progenitor cells (HSPCs) are defective. Here, we demonstrate that NUP98::HOXD13 (NHD13) MDS mice have significantly decreased functional HSPCs. Moreover, in contrast to wild-type (WT) bone marrow (BM), lineage-positive (Lin+) BM cells from NHD13 mice have self-renewal potential. Specific subsets of NHD13 Lin+ cells that express B220 and Kit antigens were able to self-renew and generate MDS in WT recipients. Although this unique B220+Kit+ phenotype could be found in WT as well as NHD13 BM, the population was markedly increased in NHD13 BM. Further characterization using Mac1 and Gr1 markers revealed that both Mac1+Gr1+B220+Kit+ and Mac1-Gr1- B220+Kit+ populations showed self-renewal and led to an MDS phenotype in WT recipients. Taken together, these findings demonstrate that as normal hematopoiesis derived from typical HSPCs decreases in NHD13 mice, committed hematopoietic progenitor cells proliferate, self-renew, and initiate MDS.","PeriodicalId":21885,"journal":{"name":"Stem Cell Reports","volume":" ","pages":"102571"},"PeriodicalIF":5.1,"publicationDate":"2025-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12365822/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144565247","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

Impaired DNA damage responses and inflammatory signaling underpin hematopoietic stem cell defects in Gata2 haploinsufficiency. 受损的DNA损伤反应和炎症信号支持造血干细胞缺陷在Gata2单倍体不全。

IF 5.1 2区医学

Stem Cell Reports Pub Date : 2025-08-12 Epub Date: 2025-07-31 DOI: 10.1016/j.stemcr.2025.102596

Ali Abdelfattah, Ahmad Habib, Leigh-Anne Thomas, Juan Bautista Menendez-Gonzalez, Alhomidi Almotiri, Hind Alqahtani, Hannah Lawson, Sarab Taha, Millie Steadman, Radhika Athalye, Alex Gibbs, Hamed Alzahrani, Ali Alshahrani, Alice Cato, Peter Giles, Alex Tonks, Ashleigh S Boyd, Kamil R Kranc, Neil P Rodrigues

{"title":"Impaired DNA damage responses and inflammatory signaling underpin hematopoietic stem cell defects in Gata2 haploinsufficiency.","authors":"Ali Abdelfattah, Ahmad Habib, Leigh-Anne Thomas, Juan Bautista Menendez-Gonzalez, Alhomidi Almotiri, Hind Alqahtani, Hannah Lawson, Sarab Taha, Millie Steadman, Radhika Athalye, Alex Gibbs, Hamed Alzahrani, Ali Alshahrani, Alice Cato, Peter Giles, Alex Tonks, Ashleigh S Boyd, Kamil R Kranc, Neil P Rodrigues","doi":"10.1016/j.stemcr.2025.102596","DOIUrl":"10.1016/j.stemcr.2025.102596","url":null,"abstract":"Clinical GATA2 haploinsufficiency results in immunodeficiency that evolves to leukemia. How GATA2 haploinsufficiency disrupts the functionality of hematopoietic stem/progenitor cells (HSCs/HSPCs) to facilitate pre-leukemia development is poorly defined. Using a hematopoietic-specific conditional mouse model of Gata2 haploinsufficiency, we identified pervasive defects in HSPC differentiation in young adult Gata2 haploinsufficient mice and perturbed HSC self-renewal following transplantation. These alterations aligned with deregulated global DNA damage responses and inflammatory cell signaling from Gata2 haploinsufficient HSCs. We also discovered genetic interplay between Gata2 and Asxl1, a secondary mutation leading to leukemia in GATA2 deficiency syndromes. HSCs from young adult compound Gata2/Asxl1 haploinsufficient mice were hyperproliferative, functionally compromised after transplantation, and displayed a broad pre-leukemia transcriptomic program. Thus, Gata2 haploinsufficiency triggers HSC genomic instability. Our data further suggest that secondary mutations like ASXL1 exploit this impaired HSC genomic integrity to nurture a pre-leukemic state in GATA2 haploinsufficiency syndromes.","PeriodicalId":21885,"journal":{"name":"Stem Cell Reports","volume":" ","pages":"102596"},"PeriodicalIF":5.1,"publicationDate":"2025-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12365849/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144765511","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

Developmental cues from epicardial cells simultaneously promote cardiomyocyte proliferation and electrochemical maturation. 来自心外膜细胞的发育线索同时促进心肌细胞增殖和电化学成熟。

IF 5.1 2区医学

Stem Cell Reports Pub Date : 2025-08-12 Epub Date: 2025-07-03 DOI: 10.1016/j.stemcr.2025.102572

Sophie E Givens, Abygail A Andebrhan, Ruchen Wang, Xiangzhen Kong, Taylor M Rothermel, Sanaz Hosseini, An Xie, Mohammad Shameem, Andrea A Torniainen, Somayeh Ebrahimi-Barough, Samuel F Boland, Maya Johnson, Natalia Calixto Mancipe, Bhairab N Singh, Samuel Dudley, Patrick W Alford, Elena G Tolkacheva, Jop H van Berlo, Brenda M Ogle

{"title":"Developmental cues from epicardial cells simultaneously promote cardiomyocyte proliferation and electrochemical maturation.","authors":"Sophie E Givens, Abygail A Andebrhan, Ruchen Wang, Xiangzhen Kong, Taylor M Rothermel, Sanaz Hosseini, An Xie, Mohammad Shameem, Andrea A Torniainen, Somayeh Ebrahimi-Barough, Samuel F Boland, Maya Johnson, Natalia Calixto Mancipe, Bhairab N Singh, Samuel Dudley, Patrick W Alford, Elena G Tolkacheva, Jop H van Berlo, Brenda M Ogle","doi":"10.1016/j.stemcr.2025.102572","DOIUrl":"10.1016/j.stemcr.2025.102572","url":null,"abstract":"Accumulating evidence indicates that maturation limits cardiomyocyte proliferation. We expand on that theory by co-culturing human induced pluripotent stem cell (hiPSC)-cardiomyocytes (CM) with epicardial cells (EPCs) and epicardial-derived cells in both 2D co-cultures and 3D engineered heart tissues (EHTs). In 2D co-cultures, the percentage of proliferating CM increased in parallel with stark electrophysiologic improvements. Single-cell transcriptomics revealed a significant shift in the bulk CM population of the epicardial-CM co-cultures as characterized by more fetal-like myofilament isoforms but with enhanced pathways associated with electrochemical maturation. The 3D-EHTs containing EPCs showed more limited proliferation but a similar improvement in CM electrophysiologic function. Next, epicardial-derived fibroblasts (EPD-FBs) were added to the EHTs containing EPCs, and we observed significant myofilament maturation and increased force generation. Our results suggest that some aspects of CM maturation (i.e., electrochemical) can occur when proliferation rates are relatively high, and that sarcomere-associated mechanical maturation occurs at later developmental stages when proliferation has largely ceased.","PeriodicalId":21885,"journal":{"name":"Stem Cell Reports","volume":" ","pages":"102572"},"PeriodicalIF":5.1,"publicationDate":"2025-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12365841/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144565246","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