Stem Cell Reports最新文献_第7页

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

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

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 5.1 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":5.1,"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

APOE4 impacts cortical neurodevelopment and alters network formation in human brain organoids. APOE4影响皮质神经发育并改变人脑类器官的网络形成。

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.2025.102537

Karina K Meyer-Acosta, Eva Diaz-Guerra, Parul Varma, Adyasha Aruk, Sara Mirsadeghi, Aranis Muniz-Perez, Yousef Rafati, Ali Hosseini, Vanesa Nieto-Estevez, Michele Giugliano, Christopher Navara, Jenny Hsieh

{"title":"APOE4 impacts cortical neurodevelopment and alters network formation in human brain organoids.","authors":"Karina K Meyer-Acosta, Eva Diaz-Guerra, Parul Varma, Adyasha Aruk, Sara Mirsadeghi, Aranis Muniz-Perez, Yousef Rafati, Ali Hosseini, Vanesa Nieto-Estevez, Michele Giugliano, Christopher Navara, Jenny Hsieh","doi":"10.1016/j.stemcr.2025.102537","DOIUrl":"10.1016/j.stemcr.2025.102537","url":null,"abstract":"Apolipoprotein E4 (APOE4) is the leading genetic risk factor for Alzheimer's disease. While most studies examine the role of APOE4 in aging, APOE4 causes persistent changes in brain structure as early as infancy and is associated with altered functional connectivity that extends beyond adolescence. Here, we used human induced pluripotent stem cell-derived cortical and ganglionic eminence organoids (COs and GEOs) to examine APOE4's influence during the development of cortical excitatory and inhibitory neurons. We show that APOE4 reduces cortical neurons and increases glia by promoting gliogenic transcriptional programs. In contrast, APOE4 increases proliferation and differentiation of GABAergic progenitors resulting in early and persistent increases in GABAergic neurons. Multi-electrode array recordings in assembloids revealed that APOE4 disrupts neural network function resulting in heightened excitability and synchronicity. Together, our data provide new insights on how APOE4 influences cortical neurodevelopmental processes and the establishment of functional networks.","PeriodicalId":21885,"journal":{"name":"Stem Cell Reports","volume":" ","pages":"102537"},"PeriodicalIF":5.9,"publicationDate":"2025-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12277819/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144337096","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

Elimination of tumorigenic pluripotent stem cells from their differentiated cell therapy products: An important step toward ensuring safe cell therapy. 从分化细胞治疗产品中去除致瘤性多能干细胞：确保细胞治疗安全的重要一步。

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.2025.102543

Afsaneh Yazdani Movahed, Rana Bagheri, Pierre Savatier, Tomo Šarić, Sharif Moradi

引用次数: 0

Cholinergic neuron-to-glioblastoma synapses in a human iPSC-derived co-culture model. 人类ipsc衍生的共培养模型中的胆碱能神经元到胶质母细胞瘤突触。

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.2025.102534

Yusha Sun, Xin Wang, Zhijian Zhang, Kristen H Park, Yicheng Wu, Weifan Dong, Daniel Y Zhang, Yao Fu, Feng Zhang, Zev A Binder, Emily Ling-Lin Pai, MacLean P Nasrallah, Kimberly M Christian, Donald M O'Rourke, Nicolas Toni, Guo-Li Ming, Hongjun Song

{"title":"Cholinergic neuron-to-glioblastoma synapses in a human iPSC-derived co-culture model.","authors":"Yusha Sun, Xin Wang, Zhijian Zhang, Kristen H Park, Yicheng Wu, Weifan Dong, Daniel Y Zhang, Yao Fu, Feng Zhang, Zev A Binder, Emily Ling-Lin Pai, MacLean P Nasrallah, Kimberly M Christian, Donald M O'Rourke, Nicolas Toni, Guo-Li Ming, Hongjun Song","doi":"10.1016/j.stemcr.2025.102534","DOIUrl":"10.1016/j.stemcr.2025.102534","url":null,"abstract":"Glioblastoma (GBM) integrates extensively into brain-wide neuronal circuits; however, neuron-tumor interactions have largely been studied with glutamatergic neurons in animal models. The role of neuromodulatory circuits for GBM biology in all-human cell systems remains unclear. Here, we report a co-culture system employing patient-derived GBM organoids and human induced pluripotent stem cell (hiPSC)-derived cholinergic neurons. We provided evidence of structural human cholinergic synaptic inputs onto GBM cells via trans-monosynaptic tracing and electron microscopy and functional synaptic interactions through the metabotropic CHRM3 receptor via calcium imaging. Deep single-cell RNA sequencing of co-cultures compared to GBM monocultures further revealed shifts in tumor transcriptional profiles toward a more proliferative state, with contributions from both diffusible factors and direct contacts, the latter of which are dependent on cholesterol biosynthesis. Together, our findings support the role of cholinergic inputs in promoting GBM progression and highlight hiPSC-derived co-culture models as a useful platform for cancer neuroscience.","PeriodicalId":21885,"journal":{"name":"Stem Cell Reports","volume":" ","pages":"102534"},"PeriodicalIF":5.9,"publicationDate":"2025-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12277791/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144337099","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

Aged human serum induces vascular changes in an isogenic co-culture venule model. 衰老人血清诱导等基因共培养小静脉模型中的血管变化。

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.2025.102544

Tracy D Chung, Raleigh M Linville, Nan Zhao, Linus Wang, Zikai Xia, Peter C Searson

{"title":"Aged human serum induces vascular changes in an isogenic co-culture venule model.","authors":"Tracy D Chung, Raleigh M Linville, Nan Zhao, Linus Wang, Zikai Xia, Peter C Searson","doi":"10.1016/j.stemcr.2025.102544","DOIUrl":"10.1016/j.stemcr.2025.102544","url":null,"abstract":"Vascular aging and dysfunction are significant contributors to age-related cardiovascular and neurodegenerative diseases. In particular, aging impacts small vessels, damaging vascular integrity leading to leakage events and inflammation, which can be further exacerbated by environmental factors. Here, we generate and evaluate an isogenic endothelial cell and pericyte venule-like co-culture model of microvasculature under perfusion with male aged human serum over 4 days. Using this model in comparison to male young human serum perfusion controls, we define the molecular and functional changes induced by aging-related circulatory cues, including functional loss of paracellular barrier integrity and modulation of transport of low-density lipoprotein. Additionally, in comparison with endothelial monoculture, we identify critical changes to basement membrane composition and aged-serum-mediated cell cycle shifts with pericyte co-culture. This modular approach reveals key impacts to further our understanding of vascular aging and to leverage in designing therapeutic and preventative approaches.","PeriodicalId":21885,"journal":{"name":"Stem Cell Reports","volume":" ","pages":"102544"},"PeriodicalIF":5.9,"publicationDate":"2025-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12277876/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144512526","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