Stem Cell ReportsPub Date : 2026-08-11Epub Date: 2026-07-23DOI: 10.1016/j.stemcr.2026.103020
Byoung-San Moon, Dae-Gyun Ahn, Jieun Park, Nhu Thi Quynh Mai, Da-Jin Jeong, Hyowon Hong, Sae-Bom Yoon, Sunhee Lee, Gun Young Yoon, Chonsaeng Kim, Keun Bon Ku, Hye Jin Nam, Ihn-Sil Kwak, Seong-Jun Kim, Heeyeong Cho
{"title":"Brain corticogenesis promotes SARS-CoV-2 neuro-glial tropism through lipid-dependent viral replication.","authors":"Byoung-San Moon, Dae-Gyun Ahn, Jieun Park, Nhu Thi Quynh Mai, Da-Jin Jeong, Hyowon Hong, Sae-Bom Yoon, Sunhee Lee, Gun Young Yoon, Chonsaeng Kim, Keun Bon Ku, Hye Jin Nam, Ihn-Sil Kwak, Seong-Jun Kim, Heeyeong Cho","doi":"10.1016/j.stemcr.2026.103020","DOIUrl":"10.1016/j.stemcr.2026.103020","url":null,"abstract":"<p><p>While extensive research has examined the neuroinvasiveness of SARS-CoV-2, its relationship with brain maturation remains unclear. Using a multi-omics approach, we established cerebral organoid (CBO) at day 60 (EB60) and day 120 (EB120) to model immature and mature developmental stages. We found that enhanced corticogenesis and gliogenesis during maturation are associated with substantial alterations in lipid metabolism, functionally linking these processes to coordinated molecular and functional brain development. Leveraging this model, we provide the first quantitative insights into long-term viral propagation kinetics up to 20 days post-infection, revealing significantly higher infectivity in mature CBOs. Single-cell transcriptomics, RT-qPCR, and immunohistochemistry revealed the upregulation of lipid-associated genes in EB120, suggesting a key driver of increased susceptibility. Consistently, pharmacological lipid reduction attenuated SARS-CoV-2 infection. Our findings establish a mechanistic link between intrinsic brain maturation and viral susceptibility mediated by lipid remodeling, suggesting lipid-lowering strategies as potential candidates for therapeutic repurposing in COVID-19.</p>","PeriodicalId":21885,"journal":{"name":"Stem Cell Reports","volume":" ","pages":"103020"},"PeriodicalIF":5.6,"publicationDate":"2026-08-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13476884/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148580109","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}
Stem Cell ReportsPub Date : 2026-08-11Epub Date: 2026-07-09DOI: 10.1016/j.stemcr.2026.103012
Pauline Antonie Ulmke, Martin N Ivanov, Hoang Duy Nguyen, Linh Pham, Asisa Muchamedin, Ayman Alzu'bi, Lora V Veleva, Tsvetomir Kachovski, Xiaoyi Mao, Krzysztof P Lubieniecki, Emil Kovachev, Gavin J Clowry, Anton B Tonchev, Huu Phuc Nguyen, Tran Tuoc
{"title":"Identification of novel genes with enriched expression in human intermediate progenitors reveals a key role for CDKN3 in cortical development.","authors":"Pauline Antonie Ulmke, Martin N Ivanov, Hoang Duy Nguyen, Linh Pham, Asisa Muchamedin, Ayman Alzu'bi, Lora V Veleva, Tsvetomir Kachovski, Xiaoyi Mao, Krzysztof P Lubieniecki, Emil Kovachev, Gavin J Clowry, Anton B Tonchev, Huu Phuc Nguyen, Tran Tuoc","doi":"10.1016/j.stemcr.2026.103012","DOIUrl":"10.1016/j.stemcr.2026.103012","url":null,"abstract":"<p><p>The evolutionary expansion of the human neocortex relies on species-specific features of intermediate progenitor cells (IPCs), including enhanced proliferation and neuronal production. The transcriptomic differences in IPCs underlying their differential capacity across species remain elusive. To identify the transcriptional signature of human IPCs (hIPCs), we isolated TBR2-positive IPCs from developing human neocortex. A comparative genome-wide expression analysis of IPC transcriptional profiles from human and mouse outlined genes preferentially expressed in hIPCs encoding key factors of cell signaling, transcriptional regulation, and proliferation. Mutations in several hIPC-specific genes were linked to cortical malformations and brain tumors. Functional experiments involving hIPC-specific overexpression of CDKN3 in developing mouse cortex validated the pivotal role of CDKN3 in IPC proliferation and neurogenesis, and supported its identification as a key determinant of hIPC biogenesis. Our findings offer new insights into the molecular features of hIPCs underlying their capacity to mediate the evolutionary expansion of the human neocortex.</p>","PeriodicalId":21885,"journal":{"name":"Stem Cell Reports","volume":" ","pages":"103012"},"PeriodicalIF":5.6,"publicationDate":"2026-08-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13476879/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148424329","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}
{"title":"Allogeneic iPSC-derived γδT cells demonstrate antitumor efficacy against patient-derived tissues.","authors":"Ryoko Futai, Michiyo Koyanagi-Aoi, Aito Nakahashi, Daiki Katsura, Manabu Horikawa, Kazumasa Horie, Yoshihiro Kakeji, Yuzo Kodama, Takashi Aoi","doi":"10.1016/j.stemcr.2026.103018","DOIUrl":"10.1016/j.stemcr.2026.103018","url":null,"abstract":"<p><p>Various immunotherapies have been developed to treat malignant tumors, and autologous CAR-T cell therapy is clinically used for certain malignancies. However, their efficacy against solid tumors is limited. γδT cells are recognized for their potent tumor cytotoxicity and MHC-unrestricted activity. We successfully induced γδT cells from iPS cells and demonstrated their cytotoxicity against colorectal cancer cell lines in vitro. However, cancer cell lines often lack critical tumor characteristics such as heterogeneity and drug sensitivity. In contrast, patient-derived cancer organoids retain many features of the patient's tumor tissues. This study evaluated the cytotoxicity of allogeneic iγδT cells against cell lines and organoids, in vitro and in vivo. iγδT cells showed 70%-90% cytotoxicity against cell lines and organoids in vitro. In vivo, local and intravenous administration of iγδT cells suppressed tumor growth by 70%-100%, highlighting their potential as a novel immunotherapy for colorectal cancer.</p>","PeriodicalId":21885,"journal":{"name":"Stem Cell Reports","volume":" ","pages":"103018"},"PeriodicalIF":5.6,"publicationDate":"2026-08-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13476892/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148580050","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}
Stem Cell ReportsPub Date : 2026-08-11Epub Date: 2026-07-23DOI: 10.1016/j.stemcr.2026.103017
Mairim Alexandra Solis, Magalys Quintana, Jesica E Candanedo P, Rita Inés Trujillo-Sagel, Lynn Chambonnet, Sulgeis Lasso
{"title":"Unproven stem cell-based interventions marketed as treatments in Panama: An urgent call for enforcement actions.","authors":"Mairim Alexandra Solis, Magalys Quintana, Jesica E Candanedo P, Rita Inés Trujillo-Sagel, Lynn Chambonnet, Sulgeis Lasso","doi":"10.1016/j.stemcr.2026.103017","DOIUrl":"10.1016/j.stemcr.2026.103017","url":null,"abstract":"<p><p>The marketing of unproven stem cell-based interventions raises public health, ethical, and regulatory challenges. This article examines online marketing in Panama, identifies new businesses, and argues that lack of enforcement has contributed to their expansion. Urgent actions are needed to mitigate this market, protect patients, and generate evidence-based treatments.</p>","PeriodicalId":21885,"journal":{"name":"Stem Cell Reports","volume":" ","pages":"103017"},"PeriodicalIF":5.6,"publicationDate":"2026-08-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13476878/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148580089","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}
Stem Cell ReportsPub Date : 2026-08-11Epub Date: 2026-07-23DOI: 10.1016/j.stemcr.2026.103021
Caroline Kokorudz, Noura Ballasy, Bethany N Radford, Anshul S Jadli, Alexa Krala, Ankita Narang, Wendy Dean, Myriam Hemberger
{"title":"The imprinted Peg3 gene is a potent regulator of the DNA methylome in trophoblast cells.","authors":"Caroline Kokorudz, Noura Ballasy, Bethany N Radford, Anshul S Jadli, Alexa Krala, Ankita Narang, Wendy Dean, Myriam Hemberger","doi":"10.1016/j.stemcr.2026.103021","DOIUrl":"10.1016/j.stemcr.2026.103021","url":null,"abstract":"<p><p>Paternally expressed gene 3 (Peg3) is an imprinted gene whose knockout (KO) causes placental and fetal growth deficits as well as maternal behavioral defects, but its molecular role remains poorly understood. Here, we report that Peg3-null trophoblast stem cells (TSCs) exhibit increased rates of mitotic errors and double-strand DNA breaks as a likely consequence of a global reduction in H3K9me3 and DNA methylation levels. Transcriptional profiling highlights a deficiency of KO cells to adequately silence genes, resulting in elevated expression levels of differentiation stage-inappropriate genes. Peg3 KO TSCs also exhibit a loss of DNA methylation and H3K9me3 at a subset of developmentally regulated CpG islands that likely rewire CTCF-regulated transcriptional networks. Collectively, our data identify PEG3 as an intrinsic component of the epigenetic repressive machinery, thus solidifying its putative role as a KRAB-ZFP protein that functions to regulate gene expression and genome integrity in the placental trophoblast lineage.</p>","PeriodicalId":21885,"journal":{"name":"Stem Cell Reports","volume":" ","pages":"103021"},"PeriodicalIF":5.6,"publicationDate":"2026-08-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13476889/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148580103","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}
Stem Cell ReportsPub Date : 2026-08-11Epub Date: 2026-07-16DOI: 10.1016/j.stemcr.2026.103013
Runxiang Qiu, Alejandra Velazquez Ojeda, Cesar Gonzalez, Vincente Abatay, Jun Wu, Dina Awabdeh, Renate Starr, Nadia Carlesso, Sarah Shuck, Yun Rose Li, Christine E Brown, Michael E Barish, Qiang Lu
{"title":"Targeting mitotic kinesin KIF20A: A differentiation-based therapeutic strategy for glioblastoma stem/progenitor cells.","authors":"Runxiang Qiu, Alejandra Velazquez Ojeda, Cesar Gonzalez, Vincente Abatay, Jun Wu, Dina Awabdeh, Renate Starr, Nadia Carlesso, Sarah Shuck, Yun Rose Li, Christine E Brown, Michael E Barish, Qiang Lu","doi":"10.1016/j.stemcr.2026.103013","DOIUrl":"10.1016/j.stemcr.2026.103013","url":null,"abstract":"<p><p>Glioblastoma multiforme (GBM) remains refractory to current treatment modalities. Differentiation-based approaches, which force cancer stem/progenitor cells to exit the cell cycle and adopt terminal fates, offer an alternative therapeutic strategy. Cell fate regulators operating during stem/progenitor cell divisions integrate proliferative and anti-proliferative cues and represent particularly attractive points of intervention. Here, we investigated the therapeutic potential of targeting mitotic kinesin KIF20A in GBM stem/progenitor cells. KIF20A is a crucial component of cytokinetic machinery and cooperates with a network of cell fate regulators to balance proliferative and differentiative divisions in neural stem/progenitor cells (NSPCs). Using complementary in vitro and in vivo models, including 2D cultures, 3D organoids, and intracranial xenografts, we show that inhibition of KIF20A drives cell cycle exit and induces a postmitotic/differentiated state in GBM stem/progenitor cells, resulting in a marked suppression of proliferation. Together, these findings establish KIF20A as a key vulnerability in GBM and a promising target for differentiation-based intervention.</p>","PeriodicalId":21885,"journal":{"name":"Stem Cell Reports","volume":" ","pages":"103013"},"PeriodicalIF":5.6,"publicationDate":"2026-08-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13476882/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148472887","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}
{"title":"Neural stem cells as potential mediators of prenatal dietary stress through epigenetic mechanisms.","authors":"Itsuki Kageyama, Hiroya Yamada, Mirai Yamazaki, Takuya Wakasugi, Yuri Kamiya, Masaki Ohshiro, Manaka Ito, Yoshiki Tsuboi, Takashi Watanabe, Genki Mizuno, Yoshitaka Ando, Hiroaki Ishikawa, Koji Suzuki, Koji Ohashi, Eiji Munetsuna","doi":"10.1016/j.stemcr.2026.102996","DOIUrl":"10.1016/j.stemcr.2026.102996","url":null,"abstract":"<p><p>The developmental origins of health and disease (DOHaD) hypothesis suggests that environmental exposures during development can induce long-term health effects, yet the cellular origin of such persistence remains unclear. Here, we suggest that neural stem cells (NSCs) may develop aberrant properties that persist with possible involvement of epigenetic mechanisms linking maternal dietary stress to neurocognitive impairments. In a rat model of maternal high-fructose corn syrup intake, offspring showed hippocampus-dependent memory deficits and reduced neurogenesis. NSCs from fetal and adolescent hippocampi exhibited persistent dysfunction with transcriptomic dysregulation. Mechanistically, transient downregulation of DNA methyltransferase 3A in fetal NSCs was associated with sustained repression of secreted phosphoprotein 1, encoding intracellular osteopontin (iOPN). iOPN overexpression partially restored NSC function, supporting a potential causal link. Our study proposes a DOHaD framework in which stem cells with lasting alterations may retain epigenetic traces of early life stress, with implications for organ systems and disease risk.</p>","PeriodicalId":21885,"journal":{"name":"Stem Cell Reports","volume":" ","pages":"102996"},"PeriodicalIF":5.6,"publicationDate":"2026-07-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13385421/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148376963","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}
{"title":"Atg5 deficiency alters myofibroblast accumulation and alveolar regeneration in lung fibrosis.","authors":"Xue Li, Guiying Xu, Qi Wang, Qingwen Ma, Xue Liu, Hongwei Li, Sisi Wang, Yimeng Liu, Yueyue Jin, Xuan Miao, Zuokuan He, Jinrui Dong, Kuan Li, Jianhai Wang, Yu Li, Qiuyang Zhang, Dianhua Jiang, Junping Wu, Wen Ning, Huaiyong Chen","doi":"10.1016/j.stemcr.2026.102979","DOIUrl":"10.1016/j.stemcr.2026.102979","url":null,"abstract":"<p><p>Lung fibrosis progression is marked by impaired alveolar epithelial regeneration and uncontrolled myofibroblast differentiation, though the underlying mechanisms remain poorly understood. In this study, we discovered that Atg5 was upregulated in the mesenchymal cells of lungs from both patients with idiopathic pulmonary fibrosis (IPF) and mice with bleomycin (BLM)-induced fibrosis. Selective deletion of Atg5 in lung mesenchymal cells increased the susceptibility of mice to BLM-induced lung fibrosis. Mechanistically, the loss of Atg5 promoted transforming growth factor β 1 (TGF-β1)-induced oxidative stress and cellular senescence in fibroblasts, myofibroblast differentiation, and extracellular matrix deposition. Intriguingly, loss of Atg5 impaired the secretion of tissue repair-favoring factors in fibroblasts, causing defects in the proliferation and differentiation of alveolar type 2 cells. This study showed that Atg5 is essential for alveolar epithelial repair and myofibroblast control in lung fibrosis.</p>","PeriodicalId":21885,"journal":{"name":"Stem Cell Reports","volume":" ","pages":"102979"},"PeriodicalIF":5.6,"publicationDate":"2026-07-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13385427/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148376989","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}
{"title":"Electron transport chain complex I and mitochondrial fusion regulate ROS for differentiation in Drosophila neural stem cells.","authors":"Rahul Kumar Verma, Atharva Bhingare, Dnyanesh Dubal, Richa Rikhy","doi":"10.1016/j.stemcr.2026.102951","DOIUrl":"10.1016/j.stemcr.2026.102951","url":null,"abstract":"<p><p>Mitochondrial fusion and electron transport chain complex I are each essential for differentiation in Drosophila neuroblasts, but the mechanism by which they interact to mediate differentiation is unknown. We found that complex I subunit depletion did not affect type II neuroblast numbers but reduced their proliferation and decreased their lineage cells. Complex I depletion decreased the mitochondrial membrane potential and cristae numbers, increased fragmentation and ROS, and inhibited Notch signaling in lineage cells. Similarly, antioxidant enzyme depletion increased ROS and reduced lineage cells. Both complex I and antioxidant proteins promoted the G1/S transition and nuclear cyclin E levels. Additional mitochondrial fusion via Drp1 mutants restored ROS levels, proliferation, and differentiation defects in complex I and antioxidant protein-depleted neuroblasts. Overexpression of antioxidant proteins and an increase in Notch signaling alleviated ROS and the complex I depletion-driven defect in neuroblast proliferation and differentiation. Complex I and mitochondrial fusion together restrict ROS to support neuroblast proliferation and differentiation.</p>","PeriodicalId":21885,"journal":{"name":"Stem Cell Reports","volume":" ","pages":"102951"},"PeriodicalIF":5.6,"publicationDate":"2026-07-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13385725/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148228522","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}
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