Stem Cell Reports最新文献

Retinoic acid signaling guides the efficiency of inner ear organoid-genesis and governs sensory-nonsensory fate specification. 视黄酸信号传导指导内耳类器官发生的效率，并控制感觉-非感觉命运规范。

IF 5.1 2区医学

Stem Cell Reports Pub Date : 2025-10-02 DOI: 10.1016/j.stemcr.2025.102671

R Keith Duncan, Liqian Liu, Mo Moyer, Andrew Wylie, Ranya Dano, Luis Cassinotti

引用次数: 0

APOL1 risk variants induce metabolic reprogramming of podocytes in patient-derived kidney organoids. APOL1风险变异诱导患者源性肾类器官足细胞代谢重编程。

IF 5.1 2区医学

Stem Cell Reports Pub Date : 2025-10-02 DOI: 10.1016/j.stemcr.2025.102650

Heein Song, Sébastien J Dumas, Gangqi Wang, Lijun Ma, Franca Witjas, M Cristina Avramut, Cathelijne W van den Berg, Michael V Rocco, Barry I Freedman, Ton J Rabelink, H Siebe Spijker

{"title":"APOL1 risk variants induce metabolic reprogramming of podocytes in patient-derived kidney organoids.","authors":"Heein Song, Sébastien J Dumas, Gangqi Wang, Lijun Ma, Franca Witjas, M Cristina Avramut, Cathelijne W van den Berg, Michael V Rocco, Barry I Freedman, Ton J Rabelink, H Siebe Spijker","doi":"10.1016/j.stemcr.2025.102650","DOIUrl":"https://doi.org/10.1016/j.stemcr.2025.102650","url":null,"abstract":"Carriers of two apolipoprotein L1 gene risk variants (RVs), termed G1 and G2, are at increased risk for chronic kidney disease. This study utilized induced pluripotent stem cells (iPSCs) derived from two patients homozygous for G1 and G2 to model human apolipoprotein L1 (APOL1)-mediated kidney disease (AMKD) in kidney organoids. Single-cell transcriptomic analysis and immunofluorescence imaging showed APOL1 upregulation in podocytes after interferon-gamma (IFN-γ) treatment. Transcriptomics and spatial dynamic metabolomics demonstrated a significant reduction in oxidative phosphorylation and tricarboxylic acid (TCA) cycle activity, along with upregulation of glycolysis and hypoxia signaling in RV podocytes. Isolated RV glomeruli exhibited no increase in maximal respiration rate following IFN-γ treatment, while iPSC-derived RV podocytes displayed a reduced number of mitochondrial branches and shorter branch length. This model presents early metabolic reprogramming of RV podocytes upon inflammatory injury and compelling evidence that mitochondrial dysfunction plays a pivotal role in the early pathophysiology of AMKD.","PeriodicalId":21885,"journal":{"name":"Stem Cell Reports","volume":" ","pages":"102650"},"PeriodicalIF":5.1,"publicationDate":"2025-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145225877","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

A novel miRNA-TF-mRNA regulatory network associated with cellular senescence in osteoporosis. 一种与骨质疏松细胞衰老相关的新型miRNA-TF-mRNA调控网络。

IF 5.1 2区医学

Stem Cell Reports Pub Date : 2025-10-02 DOI: 10.1016/j.stemcr.2025.102672

Xiang Zhang, Na Xu, Yanman Zhou, Jin Xu

{"title":"A novel miRNA-TF-mRNA regulatory network associated with cellular senescence in osteoporosis.","authors":"Xiang Zhang, Na Xu, Yanman Zhou, Jin Xu","doi":"10.1016/j.stemcr.2025.102672","DOIUrl":"https://doi.org/10.1016/j.stemcr.2025.102672","url":null,"abstract":"This study investigated the role of miR-22-3p/ESR1 axis in osteoporosis (OP) pathogenesis. Bioinformatics analysis of OP datasets and patient bone marrow samples revealed significant upregulation of miR-22-3p accompanied by downregulation of ESR1. Mechanistic validation via dual-luciferase reporter assays, RNA pull-down, and molecular docking confirmed that miR-22-3p directly targets and suppresses ESR1 expression. Functional in vitro assays in human bone marrow mesenchymal stem cells (hBMSCs) demonstrated that miR-22-3p overexpression accelerated both cellular senescence (CS) and adipogenic differentiation. Notably, this effect was reversed by ESR1 overexpression. In an aged mouse model, local intra-bone marrow administration of a miR-22-3p inhibitor effectively reduced bone marrow mesenchymal stem cell (BMSC) senescence, improved bone microstructure, and attenuated OP progression. These findings establish that the miR-22-3p-ESR1 regulatory axis critically drives OP development by coordinately promoting CS and adipogenic differentiation while suppressing osteogenesis. This pathway provides a promising mechanistic foundation for future therapeutic strategies targeting OP.","PeriodicalId":21885,"journal":{"name":"Stem Cell Reports","volume":" ","pages":"102672"},"PeriodicalIF":5.1,"publicationDate":"2025-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145225930","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

Integrated profiling of iPSC-derived motor neurons carrying C9orf72, FUS, TARDBP, or SOD1 mutations. ipsc衍生的运动神经元携带C9orf72、FUS、TARDBP或SOD1突变的综合分析。

IF 5.1 2区医学

Stem Cell Reports Pub Date : 2025-10-02 DOI: 10.1016/j.stemcr.2025.102649

Guo-Ming Ma, Cong-Cong Xia, Bo-Yu Lyu, Jie Liu, Fang Luo, Ming-Feng Guan, Jun-Ying Wang, Li Sun, Lin Zhang, Yan Chen, Ying-Wei Mao, Guo-Qiang Yu, Wen-Yuan Wang

{"title":"Integrated profiling of iPSC-derived motor neurons carrying C9orf72, FUS, TARDBP, or SOD1 mutations.","authors":"Guo-Ming Ma, Cong-Cong Xia, Bo-Yu Lyu, Jie Liu, Fang Luo, Ming-Feng Guan, Jun-Ying Wang, Li Sun, Lin Zhang, Yan Chen, Ying-Wei Mao, Guo-Qiang Yu, Wen-Yuan Wang","doi":"10.1016/j.stemcr.2025.102649","DOIUrl":"https://doi.org/10.1016/j.stemcr.2025.102649","url":null,"abstract":"Here, we conducted temporal RNA sequencing (RNA-seq) profiling of human induced pluripotent stem cells (hiPSCs) and induced pluripotent stem cell (iPSC)-derived motor neurons (iMNs) carrying C9orf72, FUS, TARDBP, or SOD1 mutations in both patients with amyotrophic lateral sclerosis (ALS) and healthy individuals. We discovered dysregulated gene expression and alternative splicing (AS) throughout iMN development and maturation, and iMNs with mutations in ALS-associated genes displayed enrichment of cytoskeletal defects and synaptic alterations from the premature stage to mature iMNs. Our findings indicate that synaptic gene dysfunction is a common molecular hallmark of familial ALS, which may result in neuronal susceptibility and progressive motor neuron degeneration. Analysis of upstream splicing factors revealed that differentially expressed RNA-binding proteins (RBPs) in iMNs from patients with ALS may cause abnormal AS events. Overall, our research provides a comprehensive and valuable resource for gaining insights into the shared mechanisms of familial ALS pathogenesis during motor neuron development and maturation in iMN models.","PeriodicalId":21885,"journal":{"name":"Stem Cell Reports","volume":" ","pages":"102649"},"PeriodicalIF":5.1,"publicationDate":"2025-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145225956","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

The novel tRF-23 promotes osteogenic differentiation of hBMSCs and protects against bone loss in ovariectomized mice. 在去卵巢小鼠中，新型tRF-23促进hBMSCs的成骨分化并防止骨质流失。

IF 5.1 2区医学

Stem Cell Reports Pub Date : 2025-10-02 DOI: 10.1016/j.stemcr.2025.102673

Haichun Liao, Wen Li, Lin Xu, Chao Zhao, Xingnuan Li, Jianjun Xiong, Tao Wang

{"title":"The novel tRF-23 promotes osteogenic differentiation of hBMSCs and protects against bone loss in ovariectomized mice.","authors":"Haichun Liao, Wen Li, Lin Xu, Chao Zhao, Xingnuan Li, Jianjun Xiong, Tao Wang","doi":"10.1016/j.stemcr.2025.102673","DOIUrl":"https://doi.org/10.1016/j.stemcr.2025.102673","url":null,"abstract":"The pathogenesis of osteoporosis is closely related to the impaired human bone marrow-derived stromal cells (hBMSCs) osteogenic differentiation. No studies to date, however, have established whether tRNA-derived fragments (tRFs) can influence osteogenic differentiation of hBMSCs or the onset of osteoporosis. Here, tRF-23 was found to control hBMSC osteogenesis through its ability to target suppressor of cytokine signaling 1 (SOCS1) via the Janus kinase 2/signal transducer and activator of transcription 3 (JAK2/STAT3) signaling pathway. tRF-23 was then further established as a potential target for efforts to protect against bone loss and marrow adipose tissue (MAT) accumulation in osteoporotic model mice, and its molecular mechanism was also verified in vivo. Together, these results suggest a model in which tRF-23 can protect against bone loss induced by ovariectomized (OVX) through the augmentation of hBMSC osteogenesis, providing a foundation for characterizing the pathogenesis of osteoporosis and seeking new therapeutic targets for this disruptive condition.","PeriodicalId":21885,"journal":{"name":"Stem Cell Reports","volume":" ","pages":"102673"},"PeriodicalIF":5.1,"publicationDate":"2025-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145226050","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

Probing DNA damage in Rett syndrome neurons uncovers a role for MECP2 regulation of PARP1. 探索Rett综合征神经元中的DNA损伤揭示了MECP2调控PARP1的作用。

IF 5.1 2区医学

Stem Cell Reports Pub Date : 2025-09-25 DOI: 10.1016/j.stemcr.2025.102645

A Morales, E Korsakova, N Mansooralavi, A Ravikumar, G Rivas, P Soliman, L Rodriguez, T McDaniel, A Lund, B Cooper, A Bhaduri, W E Lowry

引用次数: 0

A proper excitatory/inhibitory ratio is required to develop synchronized network activity in mouse cortical cultures. 在小鼠皮层培养中，需要适当的兴奋/抑制比例来发展同步的网络活动。

IF 5.1 2区医学

Stem Cell Reports Pub Date : 2025-09-25 DOI: 10.1016/j.stemcr.2025.102646

Eleonora Crocco, Ludovico Iannello, Fabrizio Tonelli, Gabriele Lagani, Luca Pandolfini, Marcello Ferro, Giuseppe Amato, Angelo Di Garbo, Federico Cremisi

{"title":"A proper excitatory/inhibitory ratio is required to develop synchronized network activity in mouse cortical cultures.","authors":"Eleonora Crocco, Ludovico Iannello, Fabrizio Tonelli, Gabriele Lagani, Luca Pandolfini, Marcello Ferro, Giuseppe Amato, Angelo Di Garbo, Federico Cremisi","doi":"10.1016/j.stemcr.2025.102646","DOIUrl":"https://doi.org/10.1016/j.stemcr.2025.102646","url":null,"abstract":"Excitatory/inhibitory (E/I) balance is thought to play a key role in cortical activity development. We modeled an in vitro cortical network deployed of the inhibitory neurons normally migrating from the ventral telencephalon and implemented ventral telencephalic (VT) cultures and co-cultures with mixed proportions of dorsal telencephalic (DT) and VT neurons, containing distinct proportions of inhibitory neurons. Interestingly, these pure and mixed cultures developed different patterns of spontaneous activity and functional connectivity. Our findings highlighted a critical role for the inhibitory component in developing correlated network activity. Unexpectedly, networks with 7% of parvalbumin (PV)+ neurons were not able to generate appreciable network burst activity due to the development of a strong network inhibition, despite their lowest E/I ratio. Our observations support the notion that an optimal ratio of PV+ neurons during cortical development is essential for the establishment of local inhibitory networks capable of generating and spreading correlated activity.","PeriodicalId":21885,"journal":{"name":"Stem Cell Reports","volume":" ","pages":"102646"},"PeriodicalIF":5.1,"publicationDate":"2025-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145178482","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

Human macula formation involves two waves of retinoic acid suppression via CYP26A1 that modulate cell cycle exit and cone subtype specification. 人类黄斑的形成涉及通过CYP26A1调节细胞周期退出和锥体亚型规范的维甲酸抑制两波。

IF 5.1 2区医学

Stem Cell Reports Pub Date : 2025-09-25 DOI: 10.1016/j.stemcr.2025.102647

Philippa Harding, Maja Wojtynska, Alexander J Smith, Robin R Ali, Rachael A Pearson

{"title":"Human macula formation involves two waves of retinoic acid suppression via CYP26A1 that modulate cell cycle exit and cone subtype specification.","authors":"Philippa Harding, Maja Wojtynska, Alexander J Smith, Robin R Ali, Rachael A Pearson","doi":"10.1016/j.stemcr.2025.102647","DOIUrl":"https://doi.org/10.1016/j.stemcr.2025.102647","url":null,"abstract":"The human macula is a specialized, cone-rich region of the eye, critical for high-acuity vision, yet the pathways regulating its development remain poorly understood. RA-catabolizing enzyme CYP26A1 establishes the chick high-acuity area via upregulation of fibroblast growth factor 8 (FGF8). However, detailed analysis of this pathway and its functions has not been performed in early human fetal tissue. Fluorescent in situ hybridization revealed striking biphasic CYP26A1 expression but little FGF8 in the presumptive macula region between post-conception weeks (PCW) 6-17. Pharmacological retinoic acid (RA) signaling inhibition in human retinal organoids mimicking the two waves of CYP26A1 revealed early RA inhibition prompted early cell cycle exit and increased cone genesis, while late inhibition altered cone subtype specification. Conversely, recombinant FGF8 had no effect on photoreceptor fate. This work provides spatiotemporal examination of CYP26A1 across human macular development, as well as experimental evidence for the different roles of RA signaling inhibition in a human model of retinal development.","PeriodicalId":21885,"journal":{"name":"Stem Cell Reports","volume":" ","pages":"102647"},"PeriodicalIF":5.1,"publicationDate":"2025-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145178514","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

How FAIR is metadata for human pluripotent stem cells? 人类多能干细胞的元数据有多公平？

IF 5.1 2区医学

Stem Cell Reports Pub Date : 2025-09-25 DOI: 10.1016/j.stemcr.2025.102644

Mengqi Hu, Rachel A Ankeny, Dan Santos, Christine A Wells

引用次数: 0

Developmental regulation of endothelial-to-hematopoietic transition from induced pluripotent stem cells. 诱导多能干细胞内皮向造血转化的发育调控。

IF 5.1 2区医学

Stem Cell Reports Pub Date : 2025-09-18 DOI: 10.1016/j.stemcr.2025.102641

Rachel Wellington, Xiaoyi Cheng, Shuvra Dutta, Clyde A Campbell, Cole Trapnell, Raquel Espin-Palazon, Brandon Hadland, Sergei Doulatov

{"title":"Developmental regulation of endothelial-to-hematopoietic transition from induced pluripotent stem cells.","authors":"Rachel Wellington, Xiaoyi Cheng, Shuvra Dutta, Clyde A Campbell, Cole Trapnell, Raquel Espin-Palazon, Brandon Hadland, Sergei Doulatov","doi":"10.1016/j.stemcr.2025.102641","DOIUrl":"10.1016/j.stemcr.2025.102641","url":null,"abstract":"Hematopoietic stem cells (HSCs) arise in embryogenesis from a specialized hemogenic endothelium (HE) via endothelial-to-hematopoietic transition (EHT). While induced pluripotent stem cells (iPSCs) give rise to HE with robust hemogenic potential, bona fide HSC generation from iPSCs remains challenging. We map single-cell dynamics of EHT from iPSCs and integrate it with human embryo datasets to identify ligand-receptor interactions that drive transcriptional divergence between iPSC-derived and embryonic cell states. The expression of endothelial genes predicted to be regulated by FGF signaling was incompletely repressed during iPSC-derived EHT. FGF activity declined at the onset of EHT to enable normal hematopoiesis in the zebrafish, and chemical inhibition of FGF signaling during EHT enhanced HSC and progenitor generation in the zebrafish and from iPSCs. In summary, we generate a single-cell map of iPSC-derived EHT, identify ligand-receptor interactions that can improve iPSC differentiation, and uncover elevated FGF signaling as a barrier to hematopoiesis.","PeriodicalId":21885,"journal":{"name":"Stem Cell Reports","volume":" ","pages":"102641"},"PeriodicalIF":5.1,"publicationDate":"2025-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145092497","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