Stem Cell Reports最新文献

BMAL1 Deficiency Contributes to Mandibular Dysplasia by Upregulating MMP3. BMAL1缺乏通过上调MMP3导致下颌发育不良。

IF 5.9 2区医学

Stem Cell Reports Pub Date : 2025-07-08 Epub Date: 2025-06-04 DOI: 10.1016/j.stemcr.2025.102541

Jiajia Zhao, Xin Zhou, Qingming Tang, Ran Yu, Shaoling Yu, Yanlin Long, Cen Cao, Jun Han, Anbing Shi, Jeremy J Mao, Xiong Chen, Lili Chen

引用次数: 0

Gustatory-neuron-supplied R-spondin-2 is required for taste bud replenishment. 味觉神经元提供的R-spondin-2是味蕾补充所必需的。

IF 5.9 2区医学

Stem Cell Reports Pub Date : 2025-07-08 Epub Date: 2025-06-19 DOI: 10.1016/j.stemcr.2025.102542

Jiang Xu, Alan Moreira de Araujo, Ranhui Xi, Kaihua Luo, Mingyue Han, Xiaoli Lin, Chanyi Lu, Minliang Zhou, Kurt D Hankenson, Robert F Margolskee, Ichiro Matsumoto, Guillaume de Lartigue, Myunghwan Choi, Peihua Jiang

{"title":"Gustatory-neuron-supplied R-spondin-2 is required for taste bud replenishment.","authors":"Jiang Xu, Alan Moreira de Araujo, Ranhui Xi, Kaihua Luo, Mingyue Han, Xiaoli Lin, Chanyi Lu, Minliang Zhou, Kurt D Hankenson, Robert F Margolskee, Ichiro Matsumoto, Guillaume de Lartigue, Myunghwan Choi, Peihua Jiang","doi":"10.1016/j.stemcr.2025.102542","DOIUrl":"10.1016/j.stemcr.2025.102542","url":null,"abstract":"Replenishment of taste cells in taste buds throughout life requires innervation. Recently, we provided evidence that R-spondin is sufficient to promote taste cell generation and restore taste buds in a nerve transection model. Yet, the necessity of gustatory-neuron-supplied R-spondin 2 (RSPO2) in taste tissue homeostasis has remained unresolved. We used genetic approaches to investigate this. In a strain that carries an Rspo2 hypomorphic allele, the number of taste buds was significantly reduced in these mice, compared to wild-type mice, in both anterior and posterior tongue. Specific ablation of Rspo2 in the nodose-petrosal-jugular ganglion complex in another mouse strain led to nearly complete loss of taste buds in the circumvallate papilla. Epithelial ablation of Rnf43/Znrf3, the activity of which is antagonized by R-spondin binding, led to exuberant, sustained expansion of taste buds. Thus, our data strongly support that the RSPO2-RNF43/ZNRF3 axis serves as a master regulator for taste tissue homeostasis.","PeriodicalId":21885,"journal":{"name":"Stem Cell Reports","volume":" ","pages":"102542"},"PeriodicalIF":5.9,"publicationDate":"2025-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12277832/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144337101","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

Lineage Tracing Reveals the Bipotency of SOX9⁺ Hepatocytes during Liver Regeneration. 谱系追踪揭示了肝脏再生过程中SOX9+肝细胞的双效性。

IF 5.9 2区医学

Stem Cell Reports Pub Date : 2025-07-08 Epub Date: 2025-06-04 DOI: 10.1016/j.stemcr.2025.102548

Ximeng Han, Yue Wang, Wenjuan Pu, Xiuzhen Huang, Lin Qiu, Yan Li, Wei Yu, Huan Zhao, Xiuxiu Liu, Lingjuan He, Libo Zhang, Yong Ji, Jie Lu, Kathy O Lui, Bin Zhou

引用次数: 0

CD37 regulates the self-renewal of leukemic stem cells via integrin-mediated signaling in acute myeloid leukemia. CD37在急性髓性白血病中通过整合素介导的信号传导调节白血病干细胞的自我更新。

IF 5.9 2区医学

Stem Cell Reports Pub Date : 2025-07-08 Epub Date: 2025-06-28 DOI: 10.1016/j.stemcr.2025.102573

Jinyuan Lu, Lixin Lv, Xiaoxue Tian, Zheng Li, Yuting Ma, Nannan Li, Jian Wang, Guangming Wang, Yu Zeng, Wenjun Zhang, Jun Xu, Aibin Liang

引用次数: 0

Engineering the next generation of allogeneic CAR cells: iPSCs as a scalable and editable platform. 设计下一代同种异体CAR细胞：iPSCs作为可扩展和可编辑的平台。

IF 5.9 2区医学

Stem Cell Reports Pub Date : 2025-07-08 Epub Date: 2025-06-05 DOI: 10.1016/j.stemcr.2025.102515

Ying Fang, Yuning Chen, Yan-Ruide Li

引用次数: 0

GSK3α negatively regulates GSK3β by decreasing its protein levels and enzymatic activity in mouse embryonic stem cells. GSK3α通过降低小鼠胚胎干细胞中GSK3β的蛋白水平和酶活性来负调控GSK3β。

IF 5.9 2区医学

Stem Cell Reports Pub Date : 2025-07-08 Epub Date: 2025-06-05 DOI: 10.1016/j.stemcr.2025.102512

Duo Wang, Xi Chen, Joshua Feng, Xueyuan A Jing, Jiaqi Tang, Jean Paul Chadarevian, Haeyoung Park, Matthew Lee, Fan Feng, Chao Zhang, Qi-Long Ying

{"title":"GSK3α negatively regulates GSK3β by decreasing its protein levels and enzymatic activity in mouse embryonic stem cells.","authors":"Duo Wang, Xi Chen, Joshua Feng, Xueyuan A Jing, Jiaqi Tang, Jean Paul Chadarevian, Haeyoung Park, Matthew Lee, Fan Feng, Chao Zhang, Qi-Long Ying","doi":"10.1016/j.stemcr.2025.102512","DOIUrl":"10.1016/j.stemcr.2025.102512","url":null,"abstract":"Glycogen synthase kinase 3 (GSK3) is a crucial regulator of cellular processes, including stem cell maintenance and differentiation. Although the roles of the two GSK3 isozymes, GSK3α and GSK3β, are well documented, their specific interactions remain less understood. In this study, we explored the regulatory interplay between GSK3α and GSK3β in mouse embryonic stem cells (mESCs). Using genetic manipulation, small-molecule inhibitors, and biochemical analysis, we found that inhibition of GSK3α kinase activity increases GSK3β protein levels and activity, whereas overexpression of GSK3α reduces GSK3β protein levels and activity. Domain-swapping experiments between the two isozymes identified the glycine-rich region at the N terminus of GSK3α as the key sequence responsible for downregulating GSK3β protein levels. Our findings reveal a novel interaction between GSK3 isozymes, with GSK3α modulating GSK3β activity to maintain the balance between stem cell pluripotency and neural differentiation. This insight may open new pathways for understanding stem cell fate mechanisms and developing GSK3-targeted therapeutic strategies in regenerative medicine.","PeriodicalId":21885,"journal":{"name":"Stem Cell Reports","volume":" ","pages":"102512"},"PeriodicalIF":5.9,"publicationDate":"2025-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12277826/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144249661","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

Vascular endothelial growth factor-induced vascular permeability results in drastic and reversible hematopoietic stem cell mobilization. 血管内皮生长因子诱导的血管通透性导致造血干细胞的剧烈和可逆的动员。

IF 5.9 2区医学

Stem Cell Reports Pub Date : 2025-07-08 Epub Date: 2025-06-26 DOI: 10.1016/j.stemcr.2025.102547

Stephanie Smith-Berdan, Mark Landon, Bryan Petkus, Leah Kramer, Alyssa Bercasio, Tuan Vo, Tobin Berger-Cahn, E Camilla Forsberg

{"title":"Vascular endothelial growth factor-induced vascular permeability results in drastic and reversible hematopoietic stem cell mobilization.","authors":"Stephanie Smith-Berdan, Mark Landon, Bryan Petkus, Leah Kramer, Alyssa Bercasio, Tuan Vo, Tobin Berger-Cahn, E Camilla Forsberg","doi":"10.1016/j.stemcr.2025.102547","DOIUrl":"10.1016/j.stemcr.2025.102547","url":null,"abstract":"Lifelong hematopoiesis as well as hematopoietic transplantation therapies is dependent on the ability of hematopoietic stem cells (HSCs) to effectively traffic across the bone marrow (BM) endothelium. Mounting evidence suggests that modulators of vascular permeability are potent regulators of HSC location. Here, we utilized a doxycycline-inducible mouse model to overexpress vascular endothelial growth factor A (VEGF-A) to alter vascular permeability. Remarkably, VEGF-induced permeability led to unprecedented HSC mobilization. HSC mobilization from the BM to the blood stream was rapid and reversible and required no additional drugs or manipulation. The mobilized HSCs were functional, as demonstrated by high levels of long-term multi-lineage reconstitution by VEGF-mobilized cells of irradiated recipients. Importantly, VEGF-induced permeability did not irrevocably destroy vascular BM niches, as transplantation experiments revealed improved long-term donor HSC engraftment in VEGF-overexpressing recipients. Collectively, these findings enhance our ability to regulate HSC trafficking to and from the BM and provide insight into improving the efficacy and safety of HSC mobilization and hematopoietic transplantation therapies.","PeriodicalId":21885,"journal":{"name":"Stem Cell Reports","volume":" ","pages":"102547"},"PeriodicalIF":5.9,"publicationDate":"2025-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12277829/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144512508","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

Microgravity accelerates skeletal muscle degeneration: Functional and transcriptomic insights from an ISS muscle lab-on-chip model. 微重力加速骨骼肌退化：来自ISS肌肉芯片实验室模型的功能和转录组学见解。

IF 5.9 2区医学

Stem Cell Reports Pub Date : 2025-07-08 Epub Date: 2025-06-26 DOI: 10.1016/j.stemcr.2025.102550

Maddalena Parafati, Zon Thwin, Legrand K Malany, Paul M Coen, Siobhan Malany

{"title":"Microgravity accelerates skeletal muscle degeneration: Functional and transcriptomic insights from an ISS muscle lab-on-chip model.","authors":"Maddalena Parafati, Zon Thwin, Legrand K Malany, Paul M Coen, Siobhan Malany","doi":"10.1016/j.stemcr.2025.102550","DOIUrl":"10.1016/j.stemcr.2025.102550","url":null,"abstract":"Microgravity accelerates skeletal muscle degeneration, mimicking aspects of aging, yet its effects on muscle cell function remain underexplored. Using a muscle lab-on-chip model onboard the International Space Station (ISS), we examined 3D-bioengineered myobundles derived from young and older adult donors under microgravity. Electrical stimulation applied intermittently to the myobundles revealed reduced contraction magnitude in microgravity and decreased protein levels of myosin heavy chain 7, a main isoform in slow-twitch muscle fibers. Transcriptomic profiling revealed active myogenesis across ground and spaceflight samples, but younger electrically stimulated myobundles displayed enhanced mitochondrial-related gene expression in microgravity, while older and non-electrically stimulated myobundles were less responsive. Comparative analysis between young and older derived myobundles identified 86 muscle-specific age-associated genes altered in microgravity, linked to inflammation, mitochondrial dysfunction, and cellular stress. These findings highlight a unique age-related molecular response in microgravity and underscores electrical stimulation as a potential countermeasure. These insights advance our understanding of muscle aging and degeneration in microgravity, guiding future therapeutic strategies.","PeriodicalId":21885,"journal":{"name":"Stem Cell Reports","volume":" ","pages":"102550"},"PeriodicalIF":5.9,"publicationDate":"2025-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12277833/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144512528","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

Telmisartan is neuroprotective in a hiPSC-derived spinal microtissue model for C9orf72 ALS via inhibition of neuroinflammation. 替米沙坦通过抑制神经炎症，在hipsc衍生的C9orf72 ALS脊髓显微组织模型中具有神经保护作用。

IF 5.9 2区医学

Stem Cell Reports Pub Date : 2025-07-08 Epub Date: 2025-06-19 DOI: 10.1016/j.stemcr.2025.102535

Berkiye Sonustun, Björn F Vahsen, Mario Ledesma-Terrón, Zhuoning Li, Laura Tuffery, Nan Xu, Elizabeth L Calder, Johannes Jungverdorben, Leslie Weber, Aaron Zhong, David G Miguez, Mara Monetti, Ting Zhou, Elisa Giacomelli, Lorenz Studer

{"title":"Telmisartan is neuroprotective in a hiPSC-derived spinal microtissue model for C9orf72 ALS via inhibition of neuroinflammation.","authors":"Berkiye Sonustun, Björn F Vahsen, Mario Ledesma-Terrón, Zhuoning Li, Laura Tuffery, Nan Xu, Elizabeth L Calder, Johannes Jungverdorben, Leslie Weber, Aaron Zhong, David G Miguez, Mara Monetti, Ting Zhou, Elisa Giacomelli, Lorenz Studer","doi":"10.1016/j.stemcr.2025.102535","DOIUrl":"10.1016/j.stemcr.2025.102535","url":null,"abstract":"Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by progressive motor neuron (MN) loss. The most common genetic cause, a hexanucleotide repeat expansion in C9orf72 (C9-ALS), disrupts microglial function, contributing to neuroinflammation, a key disease driver. To investigate this, we developed a three-dimensional spinal microtissue (SM) model incorporating human induced pluripotent stem cell (hiPSC)-derived MNs, astrocytes, and microglia. Screening 190 Food and Drug Administration (FDA)-approved compounds, we identified sartans-angiotensin II receptor I blockers (ARBs)-as potent inhibitors of neuroinflammation. Telmisartan, a highly brain-penetrant ARB, significantly reduced the levels of pro-inflammatory cytokines interleukin (IL)-6 and IL-8 and rescued MN loss in C9-ALS SMs. Our findings suggest that C9-ALS microglia drive MN toxicity and that telmisartan can effectively mitigate inflammation and preserve MN viability. This work lays the groundwork for modeling disease-related neuroinflammation and points to telmisartan as a therapeutic candidate worth further exploration for treating C9-ALS.","PeriodicalId":21885,"journal":{"name":"Stem Cell Reports","volume":" ","pages":"102535"},"PeriodicalIF":5.9,"publicationDate":"2025-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12277806/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144337012","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

Integrin β1 activity controls colony morphology during human pluripotent stem cell state transitions. 整合素β1活性控制人类多能干细胞状态转变过程中的集落形态。

IF 5.9 2区医学

Stem Cell Reports Pub Date : 2025-07-08 Epub Date: 2025-06-19 DOI: 10.1016/j.stemcr.2025.102538

Maria E Taskinen, Nicolas Pasquier, Aki Stubb, Shreya Joshi, Megan R Chastney, Paula Rasila, Sonja Vahlman, Joonas Sokka, Tapio Lönnberg, Lea Mikkola, Ras Trokovic, Johanna Ivaska

{"title":"Integrin β1 activity controls colony morphology during human pluripotent stem cell state transitions.","authors":"Maria E Taskinen, Nicolas Pasquier, Aki Stubb, Shreya Joshi, Megan R Chastney, Paula Rasila, Sonja Vahlman, Joonas Sokka, Tapio Lönnberg, Lea Mikkola, Ras Trokovic, Johanna Ivaska","doi":"10.1016/j.stemcr.2025.102538","DOIUrl":"10.1016/j.stemcr.2025.102538","url":null,"abstract":"Integrin β1-mediated adhesion is dispensable in early mouse embryogenesis (pre-implantation) but indispensable post-implantation, suggesting distinct roles for β1-integrin-mediated adhesions in the naive (pre-implantation) versus primed (post-implantation) pluripotent stem cells (PSCs). We investigated the role of integrin β1 in regulating naive-like and primed human induced PSC (hiPSC) states. We find that integrin β1 is active in both in vitro. In primed hiPSCs, integrin β1 inhibition induces naive-like colony features, reduces actomyosin contraction and extracellular signal-regulated kinase (ERK) activity, and alters gene expression, indicative of more naive-like features. These resemble the dramatic reorganization of the colony morphology, actin cytoskeleton, and adhesions upon chemical reversion from primed to naive states of pluripotency. Importantly, functional and single-cell transcriptomics analyses demonstrate that integrin β1 inhibition attenuates colony morphology transitions in cells exiting naive pluripotency. These data reveal unprecedented integrin-dependent regulation of PSC states and demonstrate how integrin inhibitors may help to fine-tune hiPSC function and properties in vitro.","PeriodicalId":21885,"journal":{"name":"Stem Cell Reports","volume":" ","pages":"102538"},"PeriodicalIF":5.9,"publicationDate":"2025-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12277811/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144337011","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