Stem Cell Reports最新文献_第2页

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

Neuroinflammation and EIF2 Signaling Persist despite Antiretroviral Treatment in an hiPSC Tri-culture Model of HIV Infection. 在HIV感染的hiPSC三培养模型中，尽管抗逆转录病毒治疗，神经炎症和EIF2信号仍然存在。

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.2025.102549

Sean K Ryan, Michael V Gonzalez, James P Garifallou, Frederick C Bennett, Kimberly S Williams, Nathaniel P Sotuyo, Eugene Mironets, Kieona Cook, Hakon Hakonarson, Stewart A Anderson, Kelly L Jordan-Sciutto

引用次数: 0

Promoting the adoption of best practices and standards to enhance quality and reproducibility of stem cell research. 促进采用最佳做法和标准，以提高干细胞研究的质量和可重复性。

IF 5.9 2区医学

Stem Cell Reports Pub Date : 2025-07-08 Epub Date: 2025-06-12 DOI: 10.1016/j.stemcr.2025.102531

Lucia Selfa Aspiroz, Milena Mennecozzi, Laura Batlle, Barbara Corneo, Lyn Healy, Mark Kotter, Andreas Kurtz, Tenneille E Ludwig, Christine Mummery, Martin Pera, Glyn N Stacey, Carlos A Tristan, Maurice Whelan

引用次数: 0

Biomanufacturing in low Earth orbit: A paradigm shift. 近地轨道生物制造：范式转变。

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.2025.102536

Davide Marotta, Noor Ward, Steven R Bauer, Joshua Hunsberger, Jana Stoudemire, Kenneth Savin, Marc Giulianotti, Catriona H M Jamieson, Donna Roberts, Michael Roberts

引用次数: 0

Graft-derived horizontal cells contribute to host-graft synapses in degenerated retinas after retinal organoid transplantation. 在视网膜类器官移植后变性视网膜中，移植物来源的水平细胞有助于宿主-移植物突触的形成。

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.2025.102545

Mikiya Watanabe, Takayuki Yamada, Hung-Ya Tu, Taro Chaya, Satoko Okayama, Kenta Onoue, Shigenobu Yonemura, Chieko Koike, Masao Tachibana, Takahisa Furukawa, Michiko Mandai

{"title":"Graft-derived horizontal cells contribute to host-graft synapses in degenerated retinas after retinal organoid transplantation.","authors":"Mikiya Watanabe, Takayuki Yamada, Hung-Ya Tu, Taro Chaya, Satoko Okayama, Kenta Onoue, Shigenobu Yonemura, Chieko Koike, Masao Tachibana, Takahisa Furukawa, Michiko Mandai","doi":"10.1016/j.stemcr.2025.102545","DOIUrl":"10.1016/j.stemcr.2025.102545","url":null,"abstract":"Stem cell-derived retinal organoid (RO) transplantation is a promising approach for treating retinal degenerative diseases such as retinitis pigmentosa. Photoreceptors (PRs) in RO sheets form synaptic connections with host bipolar cells (BCs) and improve visual function in animal models of advanced retinal degeneration. However, the contribution of horizontal cells (HCs), which are critical for PR synapse formation in the developing retina, to host-graft synapse formation remains unclear. In this study, we used HC-depleted retinal degeneration mice (rd1) and Islet1-/- genome-edited ROs (gROs) that contain HCs but not rod BCs and showed that host HC deficiency did not alter the number of host BC-graft PR synapses after transplantation into rd1, while the restored light sensitivity was enhanced in the context of host HCs. These findings indicate that graft-derived HCs alone can support host-graft synapse formation, whereas the presence of host HCs facilitates functional recovery after gRO transplantation.","PeriodicalId":21885,"journal":{"name":"Stem Cell Reports","volume":" ","pages":"102545"},"PeriodicalIF":5.9,"publicationDate":"2025-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12277844/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144512527","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

Ins and outs of HSCs and VEGF-induced vascular remodeling: Toward improved HSC mobilization and engraftment. 造血干细胞和vegf诱导的血管重塑：促进造血干细胞的动员和植入。

IF 5.9 2区医学

Stem Cell Reports Pub Date : 2025-07-08 DOI: 10.1016/j.stemcr.2025.102569

Madeline J Caduc, Simón Méndez-Ferrer

引用次数: 0

BMP, MEK, and WNT inhibition with NGN2 expression for rapid generation of hiPSC-derived neurons amenable to regional patterning. 抑制BMP、MEK和WNT与NGN2的表达，快速生成符合区域模式的hipsc衍生神经元。

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.2025.102539

Carina Habich, Alexandra Kowalski, Astrid Wachter, Michaela J Heimann, Michael Wolf, Markus P Kummer, Nathalie Nicolaisen, Christopher Sliwinski, Lydia Reinhardt, Veronika Heil, Timo Lange, Christopher Untucht, Loan N Miller, Jürgen Korffmann, Daniela Geist, David Schöndorf, Heyne Lee, Lamiaa Bahnassawy, Benjamin Mielich-Süss, Melanie S Brennan, Ruven Wilkens, Julian Röwe, Ian Weidling, Rüdiger Rudolf, Mathias Hafner, Justine D Manos, Miroslav Cik, Peter Reinhardt

{"title":"BMP, MEK, and WNT inhibition with NGN2 expression for rapid generation of hiPSC-derived neurons amenable to regional patterning.","authors":"Carina Habich, Alexandra Kowalski, Astrid Wachter, Michaela J Heimann, Michael Wolf, Markus P Kummer, Nathalie Nicolaisen, Christopher Sliwinski, Lydia Reinhardt, Veronika Heil, Timo Lange, Christopher Untucht, Loan N Miller, Jürgen Korffmann, Daniela Geist, David Schöndorf, Heyne Lee, Lamiaa Bahnassawy, Benjamin Mielich-Süss, Melanie S Brennan, Ruven Wilkens, Julian Röwe, Ian Weidling, Rüdiger Rudolf, Mathias Hafner, Justine D Manos, Miroslav Cik, Peter Reinhardt","doi":"10.1016/j.stemcr.2025.102539","DOIUrl":"10.1016/j.stemcr.2025.102539","url":null,"abstract":"Human induced pluripotent stem cells (hiPSCs) are a promising tool for studying neurological diseases and developing therapies for neurodegenerative diseases. Differentiation of hiPSCs into neurons can be achieved by dual SMAD inhibition (dSMADi) or by induced neurogenin 2 (NGN2) overexpression (\"iNGN2\"). Starting directly from hiPSCs, iNGN2 shortens the time to a neuronal stage but leads to neurons partially resembling peripheral or posterior fates while dSMADi more faithfully recapitulates telencephalic development. To modify the iNGN2 approach, we applied an accelerated induction paradigm that is dependent on the inhibition of BMP, MEK, and WNT pathways (\"BMWi\"), to commit hiPSCs into a telencephalic fate before iNGN2. The resulting neurons showed strong expression of telencephalic markers, with decreased levels of peripheral and posterior marker genes compared to iNGN2 alone. The resulting telencephalic neurons are suitable for a tau aggregation assay. Furthermore, we could demonstrate that during BMWi treatment, the cells are amenable to additional regional patterning cues. This allowed the generation of neurons from different regions of the CNS and peripheral nervous system (PNS), which will significantly facilitate in vitro modeling of a range of neurodevelopmental and neurodegenerative disorders.","PeriodicalId":21885,"journal":{"name":"Stem Cell Reports","volume":" ","pages":"102539"},"PeriodicalIF":5.9,"publicationDate":"2025-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12277818/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144337098","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