Stem Cell Reports最新文献

Human organoids: Fit for drug discovery? 人类类器官：适合药物研发？

IF 5.1 2区医学

Stem Cell Reports Pub Date : 2026-05-07 DOI: 10.1016/j.stemcr.2026.102898

Annika Wittich, Kim Krieg, Philip Gribbon, Jakob J Metzger, Alessandro Prigione, Ole Pless

引用次数: 0

Mitochondrial toxins cause widespread downregulation of pathways in X-linked dystonia-parkinsonism patient-derived neurons. 线粒体毒素导致x连锁肌张力障碍-帕金森病患者来源的神经元通路广泛下调。

IF 5.1 2区医学

Stem Cell Reports Pub Date : 2026-05-07 DOI: 10.1016/j.stemcr.2026.102920

Karen Grütz, Axel Künstner, Christin Krause, Letizia Santinelli, Sören Franzenburg, Jenny Ghelfi, Anne Grünewald, Raymond L Rosales, Norbert Brüggemann, Hauke Busch, Christine Klein, Philip Seibler

{"title":"Mitochondrial toxins cause widespread downregulation of pathways in X-linked dystonia-parkinsonism patient-derived neurons.","authors":"Karen Grütz, Axel Künstner, Christin Krause, Letizia Santinelli, Sören Franzenburg, Jenny Ghelfi, Anne Grünewald, Raymond L Rosales, Norbert Brüggemann, Hauke Busch, Christine Klein, Philip Seibler","doi":"10.1016/j.stemcr.2026.102920","DOIUrl":"https://doi.org/10.1016/j.stemcr.2026.102920","url":null,"abstract":"The genetic mechanism underlying the neurodegenerative movement disorder X-linked dystonia-parkinsonism (XDP) involves a retrotransposon insertion within the TAF1 gene. TAF1 encodes the TATA-box binding protein-associated factor 1, the largest subunit of the basal transcription factor TFIID, which connects transcription activation to the assembly of the RNA polymerase II preinitiation complex at the core promoter of genes. This study investigated how the TAF1 mutation affects the transcriptomes of XDP patient-derived neurons under basal conditions and in response to mitochondrial toxins. Gene set enrichment analysis revealed that, under basal conditions, patient-derived neurons exhibited predominantly upregulated pathways compared to controls. However, exposure to mitochondrial toxins induced a global shift toward downregulation of pathways in XDP neurons, affecting genome maintenance, epigenetic regulation, adaptive neuronal function, and transcription. Our findings suggest that neurons from XDP patients are more susceptible to mitochondrial stress than controls, leading to widespread transcriptomic downregulation and increased DNA damage.","PeriodicalId":21885,"journal":{"name":"Stem Cell Reports","volume":" ","pages":"102920"},"PeriodicalIF":5.1,"publicationDate":"2026-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147857309","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

Therapeutic reactivation of hippocampal progenitors reverse cognition decline in mice with progressive brain demyelination. 海马祖细胞的治疗性再激活逆转了进行性脑脱髓鞘小鼠的认知能力下降。

IF 5.1 2区医学

Stem Cell Reports Pub Date : 2026-04-30 DOI: 10.1016/j.stemcr.2026.102896

Shiva Nemati, Seyed Mojtaba Hosseini, Maria Astrid Bravo-Jimenez, Soheila Karimi-Abdolrezaee

{"title":"Therapeutic reactivation of hippocampal progenitors reverse cognition decline in mice with progressive brain demyelination.","authors":"Shiva Nemati, Seyed Mojtaba Hosseini, Maria Astrid Bravo-Jimenez, Soheila Karimi-Abdolrezaee","doi":"10.1016/j.stemcr.2026.102896","DOIUrl":"https://doi.org/10.1016/j.stemcr.2026.102896","url":null,"abstract":"Chronic brain demyelination and neurodegeneration are hallmarks of progressive multiple sclerosis (MS) that underlie cognitive impairments. Neural precursor cells (NPCs) in the hippocampus support cognition through neurogenesis. With MS chronicity, neurogenesis declines leading to memory impairments. The mechanisms that drive NPC quiescence in MS are largely unknown. Here, we link downregulation of neuregulin-1 (NRG-1) to diminished self-renewal, activity and neurogenesis of NPCs, and hippocampal neurodegeneration and memory decline in mice with chronic demyelination. NRG-1 is a key signaling protein for neural differentiation and function that we previously reported its dysregulation in chronic active lesions of human secondary progressive MS (SPMS). We show that NRG-1 restoration reactivates NPCs and foster hippocampal repair by supporting neurogenesis, neuronal complexity, synaptogenesis, and remyelination that reverse memory impairments. Compared with Siponimod, a current disease modifying therapy for SPMS, NRG-1 achieved greater and multifaceted reparative effects, highlighting its potential as a regenerative therapy for progressive MS.","PeriodicalId":21885,"journal":{"name":"Stem Cell Reports","volume":" ","pages":"102896"},"PeriodicalIF":5.1,"publicationDate":"2026-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147820915","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

TOE1 is a β-catenin interacting protein regulating the proliferation of hematopoietic cells through PAK2 modulation. TOE1是一种β-连环蛋白相互作用蛋白，通过PAK2调节造血细胞的增殖。

IF 5.1 2区医学

Stem Cell Reports Pub Date : 2026-04-23 DOI: 10.1016/j.stemcr.2026.102894

Hyun Park, Okan Sevim, Megan Wagstaff, Aaron Goff, David A Palmer, Bomee Kim, Kate Heesom, Allison Blair, Sarah F Newbury, Ethan L Morgan, Benjamin P Towler, Timothy J Chevassut, Rhys G Morgan

{"title":"TOE1 is a β-catenin interacting protein regulating the proliferation of hematopoietic cells through PAK2 modulation.","authors":"Hyun Park, Okan Sevim, Megan Wagstaff, Aaron Goff, David A Palmer, Bomee Kim, Kate Heesom, Allison Blair, Sarah F Newbury, Ethan L Morgan, Benjamin P Towler, Timothy J Chevassut, Rhys G Morgan","doi":"10.1016/j.stemcr.2026.102894","DOIUrl":"https://doi.org/10.1016/j.stemcr.2026.102894","url":null,"abstract":"Acute myeloid leukemia (AML) is an aggressive hematological malignancy frequently exhibiting deregulated expression/activity/localization of the Wnt signaling mediator β-catenin. To derive more effective β-catenin targeting strategies, we previously interrogated its interaction network in myeloid cells and identified several putative novel interacting partners, including Target of EGR1 (TOE1); a deadenylase with unknown function in hematological tissue. This study aimed to define TOE1 function in hematopoietic cells and uncover its molecular targets. TOE1 interacted with β-catenin in both primary and immortalized AML cells, and impacted Wnt signaling output through the modulation of lymphoid enhancer-binding factor-1 (LEF-1). AML samples exhibited deregulated TOE1 expression versus normal hematopoietic stem/progenitor cells (HSPCs), and TOE1 depletion suppressed the proliferation of myeloid leukemia cell lines, and primary human HSPCs, partly through a p21-activated-kinase 2 (PAK2) mediated mechanism. In summary, these data reveal TOE1 as a novel regulator of hematopoietic cell proliferation via the modulation of important growth-regulating pathways.","PeriodicalId":21885,"journal":{"name":"Stem Cell Reports","volume":" ","pages":"102894"},"PeriodicalIF":5.1,"publicationDate":"2026-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147781559","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

MECP2 mutations rewire human ESC fate and bias cortical lineage commitment. MECP2突变重新连接人类ESC命运，并偏向皮质谱系承诺。

IF 5.1 2区医学

Stem Cell Reports Pub Date : 2026-04-23 DOI: 10.1016/j.stemcr.2026.102895

Marion Guillon, Margaux Brin, Elodie Gabet, Justine Gromaire, Mathéa Bernard, Laetitia Laurent, Théo Rabin, Lisa Bianchin, Marie Veziano, Julie Kloda, Alexia Bernard, Laila Asali, Yi Liu, Anthony Flamier

{"title":"MECP2 mutations rewire human ESC fate and bias cortical lineage commitment.","authors":"Marion Guillon, Margaux Brin, Elodie Gabet, Justine Gromaire, Mathéa Bernard, Laetitia Laurent, Théo Rabin, Lisa Bianchin, Marie Veziano, Julie Kloda, Alexia Bernard, Laila Asali, Yi Liu, Anthony Flamier","doi":"10.1016/j.stemcr.2026.102895","DOIUrl":"https://doi.org/10.1016/j.stemcr.2026.102895","url":null,"abstract":"Rett syndrome arises from loss-of-function mutations in the X-linked chromatin regulator MECP2, yet the earliest molecular derailments in development are poorly defined. Using isogenic human embryonic stem cell (hESC) models carrying three patient-derived MECP2 mutations, we followed the transcriptome from pluripotency through neuroectoderm, neural stem/progenitor stages. Developmental stage dominated transcriptional variance, but mutants shared a secondary program enriched for synaptic-membrane and extracellular matrix genes. Single-cell/bulk profiling at the embryonic stem cell (ESC) stage revealed partial naïve-like drift, marked by the up-regulation of the naïve-enriched factor ZFP42/REX1 and related markers in MECP2-mutant lines. Among convergently dysregulated genes, the cortical determinant EMX1 showed an abnormal developmental trajectory, early repression followed by overshoot, and was consistently altered across independent Rett PSC models. Single-nucleus RNA-seq of cerebral organoids uncovered allele-specific yet convergent disturbances in cortical lineage allocation. These data chart a continuous developmental trajectory for MECP2-mutant cells and nominate naïve-like drift and mis-timed EMX1 expression as tractable entry points for dissecting Rett pathogenesis.","PeriodicalId":21885,"journal":{"name":"Stem Cell Reports","volume":" ","pages":"102895"},"PeriodicalIF":5.1,"publicationDate":"2026-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147781564","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

Organoid phenotypic screening identified glycyrrhizin that confers protection against tumor necrosis factor-induced cell death. 类器官表型筛选鉴定出甘草酸对肿瘤坏死因子诱导的细胞死亡具有保护作用。

IF 5.1 2区医学

Stem Cell Reports Pub Date : 2026-04-16 DOI: 10.1016/j.stemcr.2026.102891

Yu Takahashi, Zhongwei Zhang, Izumi Tanaka, I-Ting Lee, Jincheng He, Yurina Koura, Shintaro Sato, Hirotatsu Kojima, Takayoshi Okabe, Hiroshi Kiyono, Takashi Sasaki, Yoshio Yamauchi, Yosuke Kurashima, Ryuichiro Sato

{"title":"Organoid phenotypic screening identified glycyrrhizin that confers protection against tumor necrosis factor-induced cell death.","authors":"Yu Takahashi, Zhongwei Zhang, Izumi Tanaka, I-Ting Lee, Jincheng He, Yurina Koura, Shintaro Sato, Hirotatsu Kojima, Takayoshi Okabe, Hiroshi Kiyono, Takashi Sasaki, Yoshio Yamauchi, Yosuke Kurashima, Ryuichiro Sato","doi":"10.1016/j.stemcr.2026.102891","DOIUrl":"https://doi.org/10.1016/j.stemcr.2026.102891","url":null,"abstract":"Human organoids are considered physiological models that reflect human physiology; however, their applications in drug screening studies are limited. To develop a fundamental treatment for recurrent Crohn's disease (CD), in which tumor necrosis factor (TNF) is a key pathogenic factor, we conducted phenotypic drug screening to prevent TNF-induced cell death in human intestinal epithelial organoids. Glycyrrhizin, a natural product of licorice root, dose-dependently blocked TNF-induced cell death in organoids but not in TNF-sensitive L929 cells; L929 cells exhibited necroptosis, whereas organoid-derived cells preferentially showed apoptosis upon TNF treatment, determining the specificity of glycyrrhizin. Glycyrrhizin inhibited downstream caspase-8 signaling, which is essential for TNF-dependent apoptosis, and ameliorated intestinal inflammation in vivo. These results demonstrate that glycyrrhizin may be a novel therapeutic compound for CD and highlight the importance of using organoids for phenotypic drug screening.","PeriodicalId":21885,"journal":{"name":"Stem Cell Reports","volume":" ","pages":"102891"},"PeriodicalIF":5.1,"publicationDate":"2026-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147718169","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

An optimized protocol for efficient derivation of pancreatic islets from multiple human pluripotent stem cell lines. 从多种人类多能干细胞系高效衍生胰岛的优化方案。

IF 5.1 2区医学

Stem Cell Reports Pub Date : 2026-04-16 DOI: 10.1016/j.stemcr.2026.102892

Siqin Wu, Shivam Chandel, Galyna Bryzgalova, Paschalis Efstathopoulos, Kelly Blust, Cheng Zhao, Eda Erbil, Anna Falk, My Hedhammar, Per-Olof Berggren, Fredrik Lanner

{"title":"An optimized protocol for efficient derivation of pancreatic islets from multiple human pluripotent stem cell lines.","authors":"Siqin Wu, Shivam Chandel, Galyna Bryzgalova, Paschalis Efstathopoulos, Kelly Blust, Cheng Zhao, Eda Erbil, Anna Falk, My Hedhammar, Per-Olof Berggren, Fredrik Lanner","doi":"10.1016/j.stemcr.2026.102892","DOIUrl":"https://doi.org/10.1016/j.stemcr.2026.102892","url":null,"abstract":"The success of cell therapy for type 1 diabetes (T1D) depends on reliable differentiation of stem cells into functional pancreatic islets. Current protocols produce stem cell-derived islets (SC-islets) that contain non-endocrine cells and show limited maturity. We developed a robust protocol that generates functional SC-islets from all eight tested human pluripotent stem cell (hPSC) lines. Differentiation to the endocrine progenitor (EP) stage on 2D laminin-521 is improved by shortening the prior pancreatic progenitor (PP) stage. Notably, allowing EP cells to self-aggregate efficiently removes proliferative and non-endocrine cells. Subsequent suspension culture yields SC-islets with strong glucose responsiveness in vitro. After transplantation into the anterior chamber of the eye of diabetic mice, SC-islets further mature and restore normal glycemic control. Single-cell analyses show that the SC-islets are free of non-endocrine cell populations before and after transplantation. This protocol enables production of highly functional SC-islets suitable for T1D cell therapy.","PeriodicalId":21885,"journal":{"name":"Stem Cell Reports","volume":" ","pages":"102892"},"PeriodicalIF":5.1,"publicationDate":"2026-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147718193","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

Cytoarchitecture of neurogenic niche and neuroblast clusters in the postnatal microminipig brain. 出生后微型猪脑中神经源性生态位和神经母细胞簇的细胞结构。

IF 5.1 2区医学

Stem Cell Reports Pub Date : 2026-04-16 DOI: 10.1016/j.stemcr.2026.102893

Daijiro Kojima, Masato Sawada, Taisei Ishimaru, Nodoka Ito, Shinichiro Tateyama, Kazuhide Adachi, Hiroaki Kawaguchi, Noriaki Satake, Vicente Herranz-Pérez, José Manuel García-Verdugo, Yuichi Hirose, Nobuhiko Ohno, Naoko Kaneko, Kazunobu Sawamoto

{"title":"Cytoarchitecture of neurogenic niche and neuroblast clusters in the postnatal microminipig brain.","authors":"Daijiro Kojima, Masato Sawada, Taisei Ishimaru, Nodoka Ito, Shinichiro Tateyama, Kazuhide Adachi, Hiroaki Kawaguchi, Noriaki Satake, Vicente Herranz-Pérez, José Manuel García-Verdugo, Yuichi Hirose, Nobuhiko Ohno, Naoko Kaneko, Kazunobu Sawamoto","doi":"10.1016/j.stemcr.2026.102893","DOIUrl":"https://doi.org/10.1016/j.stemcr.2026.102893","url":null,"abstract":"The ventricular-subventricular zone (V-SVZ) is the largest neurogenic niche in the postnatal mammalian brain, but its organization and migratory dynamics remain poorly understood in gyrencephalic species. Here, we provide ultrastructural and three-dimensional characterization of the V-SVZ neuroblasts in postnatal microminipigs, the smallest pig strain with unique advantages for experimental neuroscience. Transmission electron microscopy revealed developmental changes in cell composition and cytoarchitecture, with migratory neuroblasts consistently associated with glial cells and vasculatures. Notably, serial block-face scanning electron microscopy revealed that tier 3 neuroblasts, a gyrencephalic-specific population, formed elongated, chain-like clusters aligned along vessels, with conserved intracellular features such as polarized organelle distributions and growth cone extension. Radial glial fibers were prominent in neonates but diminished with age, suggesting a developmental shift to vascular scaffolds as primary migration guides. These findings establish microminipigs as a tractable gyrencephalic model for studying postnatal neurogenesis, offering new opportunities for translational research on brain repair.","PeriodicalId":21885,"journal":{"name":"Stem Cell Reports","volume":" ","pages":"102893"},"PeriodicalIF":5.1,"publicationDate":"2026-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147718144","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

Anesthetic-induced neurodevelopmental changes with region-specific responses to propofol in forebrain organoids. 麻醉诱导的神经发育变化与异丙酚在前脑类器官中的区域特异性反应。

IF 5.1 2区医学

Stem Cell Reports Pub Date : 2026-04-14 Epub Date: 2026-03-19 DOI: 10.1016/j.stemcr.2026.102859

Hong-Qing She, Chang-Le Fang, Qi-Jun Li, Ruo-Lan Du, Ke-Qian Liu, Qiu-Xia Xiao, Xiao-He Tian, Wen-Yuan Wang, Liu-Lin Xiong

引用次数: 0

A humanized engineered heart tissue platform for cardiotoxicity assessment. 一种用于心脏毒性评估的人源化工程心脏组织平台。

IF 5.1 2区医学

Stem Cell Reports Pub Date : 2026-04-14 Epub Date: 2026-03-19 DOI: 10.1016/j.stemcr.2026.102856

Yao-Hui Sun, Daphne A Diloretto, Hillary K J Kao, Padmini Sirish, Christophe Morisseau, Rasheed Sule, Ming-Fo Hsu, Regan L Smithers, James Overton, Valeriy Timofeyev, Alexander Merleev, Gabriela Grigorean, Brett S Phinney, Emanual M Maverakis, Aldrin V Gomes, Fawaz G Haj, Jan A Nolta, James W Chan, Bruce D Hammock, Deborah K Lieu, Nipavan Chiamvimonvat

{"title":"A humanized engineered heart tissue platform for cardiotoxicity assessment.","authors":"Yao-Hui Sun, Daphne A Diloretto, Hillary K J Kao, Padmini Sirish, Christophe Morisseau, Rasheed Sule, Ming-Fo Hsu, Regan L Smithers, James Overton, Valeriy Timofeyev, Alexander Merleev, Gabriela Grigorean, Brett S Phinney, Emanual M Maverakis, Aldrin V Gomes, Fawaz G Haj, Jan A Nolta, James W Chan, Bruce D Hammock, Deborah K Lieu, Nipavan Chiamvimonvat","doi":"10.1016/j.stemcr.2026.102856","DOIUrl":"10.1016/j.stemcr.2026.102856","url":null,"abstract":"Cardiovascular diseases (CVDs), many of which are influenced by exposure to environmental xenobiotics, lack physiologically relevant in vitro models for cardiotoxicity assessment. Although some pollutants have established associations with CVD, the effects of a wide range of potential toxicants remains unknown. Here, we developed a three-dimensional recellularized humanized engineered heart tissue (rHHT) platform by integrating decellularized human left ventricular extracellular matrix with human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs), yielding spontaneously contracting tissues that recapitulate key features of native ventricular myocardium. We also generated a hiPSC line stably expressing the calcium indicator GCaMP6f, enabling real-time and longitudinal monitoring of calcium transients. Using ethanol and rotenone as examples, we demonstrate that the rHHT platform provides a sensitive system for evaluating cardiotoxicity and is more stringent than conventional monolayer approaches. This study presents a scalable platform for xenobiotic cardiotoxicity assessment, with potential applicability to high-throughput screening, mechanistic studies, and future personalized medicine applications.","PeriodicalId":21885,"journal":{"name":"Stem Cell Reports","volume":" ","pages":"102856"},"PeriodicalIF":5.1,"publicationDate":"2026-04-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13083795/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147491779","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