Stem Cell Reports最新文献_第2页

Optimized prime editing of the Alzheimer's disease-associated APOE4 mutation.

IF 5.9 2区医学

Stem Cell Reports Pub Date : 2024-12-05 DOI: 10.1016/j.stemcr.2024.11.002

Antje K Rottner, Anders Lundin, Songyuan Li, Mike Firth, Marcello Maresca, Grzegorz Sienski

引用次数: 0

A versatile in vivo platform for reversible control of transgene expression in adult tissues.

IF 5.9 2区医学

Stem Cell Reports Pub Date : 2024-12-05 DOI: 10.1016/j.stemcr.2024.11.003

Jumpei Taguchi, Yosuke Yamada, Sho Ohta, Fumie Nakasuka, Takuya Yamamoto, Manabu Ozawa, Yasuhiro Yamada

{"title":"A versatile in vivo platform for reversible control of transgene expression in adult tissues.","authors":"Jumpei Taguchi, Yosuke Yamada, Sho Ohta, Fumie Nakasuka, Takuya Yamamoto, Manabu Ozawa, Yasuhiro Yamada","doi":"10.1016/j.stemcr.2024.11.003","DOIUrl":"10.1016/j.stemcr.2024.11.003","url":null,"abstract":"Temporal control of transgenes has advanced biomedical interventions, including in vivo reprogramming, often utilizing the doxycycline (Dox)-mediated Tet-ON system. Here, we developed the Dox-mediated Tet-ON or complementary Tet-OFF counterpart to thoroughly investigate spatial and temporal transgene regulation in adult tissues, revealing inherent limitations and unexpected capabilities of each system. In stark contrast with the Tet-ON system, which was effective only in particular tissues and cell types, primarily epithelial cells, the Tet-OFF system proved capable of gene induction across diverse cell types. Despite the drawback of the Tet-OFF system in inducibility and tunability identified in our study, we demonstrated that use of tetracycline (Tc) effectively addresses these issues, possibly through its pharmacologic properties. Our data suggest that the Tc-mediated Tet-OFF system not only enables more versatile control of transgene expression but also offers a more biocompatible alternative for in vivo applications such as tissue regeneration and organismal rejuvenation.","PeriodicalId":21885,"journal":{"name":"Stem Cell Reports","volume":" ","pages":"102373"},"PeriodicalIF":5.9,"publicationDate":"2024-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142791708","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

Targeting glioblastoma with a brain-penetrant drug that impairs brain tumor stem cells via NLE1-Notch1 complex. 通过 NLE1-Notch1 复合物损害脑肿瘤干细胞的脑穿刺药物靶向胶质母细胞瘤。

IF 5.9 2区医学

Stem Cell Reports Pub Date : 2024-11-12 Epub Date: 2024-10-17 DOI: 10.1016/j.stemcr.2024.09.007

Audrey Burban, Ahmad Sharanek, Aldo Hernandez-Corchado, Hamed S Najafabadi, Vahab D Soleimani, Arezu Jahani-Asl

{"title":"Targeting glioblastoma with a brain-penetrant drug that impairs brain tumor stem cells via NLE1-Notch1 complex.","authors":"Audrey Burban, Ahmad Sharanek, Aldo Hernandez-Corchado, Hamed S Najafabadi, Vahab D Soleimani, Arezu Jahani-Asl","doi":"10.1016/j.stemcr.2024.09.007","DOIUrl":"10.1016/j.stemcr.2024.09.007","url":null,"abstract":"Brain tumor stem cells (BTSCs) are a population of self-renewing malignant stem cells that play an important role in glioblastoma tumor hierarchy and contribute to tumor growth, therapeutic resistance, and tumor relapse. Thus, targeting of BTSCs within the bulk of tumors represents a crucial therapeutic strategy. Here, we report that edaravone is a potent drug that impairs BTSCs in glioblastoma. We show that edaravone inhibits the self-renewal and growth of BTSCs harboring a diverse range of oncogenic mutations without affecting non-oncogenic neural stem cells. Global gene expression analysis revealed that edaravone significantly alters BTSC transcriptome and attenuates the expression of a large panel of genes involved in cell cycle progression, stemness, and DNA repair mechanisms. Mechanistically, we discovered that edaravone directly targets Notchless homolog 1 (NLE1) and impairs Notch signaling pathway, alters the expression of stem cell markers, and sensitizes BTSC response to ionizing radiation (IR)-induced cell death. Importantly, we show that edaravone treatment in preclinical models delays glioblastoma tumorigenesis, sensitizes their response to IR, and prolongs the lifespan of animals. Our data suggest that repurposing of edaravone is a promising therapeutic strategy for patients with glioblastoma.","PeriodicalId":21885,"journal":{"name":"Stem Cell Reports","volume":" ","pages":"1534-1547"},"PeriodicalIF":5.9,"publicationDate":"2024-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11589194/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142475174","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

Guardians of the mind: Calvarial stem cells and brain border immunity. 心灵的守护者钙质干细胞与脑边界免疫力

IF 5.9 2区医学

Stem Cell Reports Pub Date : 2024-11-12 Epub Date: 2024-10-31 DOI: 10.1016/j.stemcr.2024.10.002

Bo Li

引用次数: 0

Transplantation of human pluripotent stem cell-derived retinal sheet in a primate model of macular hole. 在灵长类动物黄斑孔模型中移植人类多能干细胞衍生视网膜片。

IF 5.9 2区医学

Stem Cell Reports Pub Date : 2024-11-12 Epub Date: 2024-10-03 DOI: 10.1016/j.stemcr.2024.09.002

Yasuaki Iwama, Yasuko Sugase-Miyamoto, Kenta Onoue, Hirofumi Uyama, Keiji Matsuda, Kazuko Hayashi, Ryutaro Akiba, Tomohiro Masuda, Satoshi Yokota, Shigenobu Yonemura, Kohji Nishida, Masayo Takahashi, Yasuo Kurimoto, Michiko Mandai

{"title":"Transplantation of human pluripotent stem cell-derived retinal sheet in a primate model of macular hole.","authors":"Yasuaki Iwama, Yasuko Sugase-Miyamoto, Kenta Onoue, Hirofumi Uyama, Keiji Matsuda, Kazuko Hayashi, Ryutaro Akiba, Tomohiro Masuda, Satoshi Yokota, Shigenobu Yonemura, Kohji Nishida, Masayo Takahashi, Yasuo Kurimoto, Michiko Mandai","doi":"10.1016/j.stemcr.2024.09.002","DOIUrl":"10.1016/j.stemcr.2024.09.002","url":null,"abstract":"Macular hole (MH) is a retinal break involving the fovea that causes impaired vision. Although advances in vitreoretinal surgical techniques achieve >90% MH closure rate, refractory cases still exist. For such cases, autologous retinal transplantation is an optional therapy showing good anatomic success, but visual improvement is limited and peripheral visual field defects are inevitable after graft harvesting. Here, using a non-human primate model, we evaluated whether human embryonic stem cell-derived retinal organoid (RO) sheet transplantation can be an effective option for treating MH. After transplantation, MH was successfully closed by continuous filling of the MH space with the RO sheet, resulting in improved visual function, although no host-graft synaptic connections were confirmed. Mild xeno-transplantation rejection was controlled by additional focal steroid injections and rod/cone photoreceptors developed in the graft. Overall, our findings suggest pluripotent stem cell-derived RO sheet transplantation as a practical option for refractory MH treatment.","PeriodicalId":21885,"journal":{"name":"Stem Cell Reports","volume":" ","pages":"1524-1533"},"PeriodicalIF":5.9,"publicationDate":"2024-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11589285/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142376046","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

The urgent need for clear and concise regulations on exosome-based interventions. 亟需对基于外泌体的干预措施制定简明扼要的规定。

IF 5.9 2区医学

Stem Cell Reports Pub Date : 2024-11-12 Epub Date: 2024-10-24 DOI: 10.1016/j.stemcr.2024.09.008

Misao Fujita, Taichi Hatta, Tsunakuni Ikka, Tatsuo Onishi

引用次数: 0

Validation of non-destructive morphology-based selection of cerebral cortical organoids by paired morphological and single-cell RNA-seq analyses. 通过配对形态学和单细胞RNA-seq分析验证基于非破坏性形态学的大脑皮质有器官选择。

IF 5.9 2区医学

Stem Cell Reports Pub Date : 2024-11-12 Epub Date: 2024-10-10 DOI: 10.1016/j.stemcr.2024.09.005

Megumi Ikeda, Daisuke Doi, Hayao Ebise, Yuki Ozaki, Misaki Fujii, Tetsuhiro Kikuchi, Kenji Yoshida, Jun Takahashi

引用次数: 0

Genome-wide screening reveals essential roles for HOX genes and imprinted genes during caudal neurogenesis of human embryonic stem cells. 全基因组筛选揭示了 HOX 基因和印记基因在人类胚胎干细胞尾部神经发生过程中的重要作用。

IF 5.9 2区医学

Stem Cell Reports Pub Date : 2024-11-12 Epub Date: 2024-10-31 DOI: 10.1016/j.stemcr.2024.09.009

Shay Kinreich, Anna Bialer-Tsypin, Ruth Viner-Breuer, Gal Keshet, Roni Suhler, Patrick Siang Lin Lim, Tamar Golan-Lev, Ofra Yanuka, Adi Turjeman, Oren Ram, Eran Meshorer, Dieter Egli, Atilgan Yilmaz, Nissim Benvenisty

{"title":"Genome-wide screening reveals essential roles for HOX genes and imprinted genes during caudal neurogenesis of human embryonic stem cells.","authors":"Shay Kinreich, Anna Bialer-Tsypin, Ruth Viner-Breuer, Gal Keshet, Roni Suhler, Patrick Siang Lin Lim, Tamar Golan-Lev, Ofra Yanuka, Adi Turjeman, Oren Ram, Eran Meshorer, Dieter Egli, Atilgan Yilmaz, Nissim Benvenisty","doi":"10.1016/j.stemcr.2024.09.009","DOIUrl":"10.1016/j.stemcr.2024.09.009","url":null,"abstract":"Mapping the essential pathways for neuronal differentiation can uncover new therapeutics and models for neurodevelopmental disorders. We thus utilized a genome-wide loss-of-function library in haploid human embryonic stem cells, differentiated into caudal neuronal cells. We show that essential genes for caudal neurogenesis are enriched for secreted and membrane proteins and that a large group of neurological conditions, including neurodegenerative disorders, manifest early neuronal phenotypes. Furthermore, essential transcription factors are enriched with homeobox (HOX) genes demonstrating synergistic regulation and surprising non-redundant functions between HOXA6 and HOXB6 paralogs. Moreover, we establish the essentialome of imprinted genes during neurogenesis, demonstrating that maternally expressed genes are non-essential in pluripotent cells and their differentiated germ layers, yet several are essential for neuronal development. These include Beckwith-Wiedemann syndrome- and Angelman syndrome-related genes, for which we suggest a novel regulatory pathway. Overall, our work identifies essential pathways for caudal neuronal differentiation and stage-specific phenotypes of neurological disorders.","PeriodicalId":21885,"journal":{"name":"Stem Cell Reports","volume":" ","pages":"1598-1619"},"PeriodicalIF":5.9,"publicationDate":"2024-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11589199/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142565036","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

Accelerated mitochondrial dynamics promote spermatogonial differentiation. 线粒体动力学的加速促进了精原细胞的分化。

IF 5.9 2区医学

Stem Cell Reports Pub Date : 2024-11-12 Epub Date: 2024-10-10 DOI: 10.1016/j.stemcr.2024.09.006

Zhaoran Zhang, Junru Miao, Hanben Wang, Izza Ali, Duong Nguyen, Wei Chen, Yuan Wang

{"title":"Accelerated mitochondrial dynamics promote spermatogonial differentiation.","authors":"Zhaoran Zhang, Junru Miao, Hanben Wang, Izza Ali, Duong Nguyen, Wei Chen, Yuan Wang","doi":"10.1016/j.stemcr.2024.09.006","DOIUrl":"10.1016/j.stemcr.2024.09.006","url":null,"abstract":"At different stages of spermatogenesis, germ cell mitochondria differ remarkably in morphology, architecture, and functions. However, it remains elusive how mitochondria change their features during spermatogonial differentiation, which in turn impacts spermatogonial stem cell fate decision. In this study, we observed that mitochondrial fusion and fission were both upregulated during spermatogonial differentiation. As a result, the mitochondrial morphology remained unaltered. Enhanced mitochondrial fusion and fission promoted spermatogonial differentiation, while the deficiency in DRP1-mediated fission led to a stage-specific blockage of spermatogenesis at differentiating spermatogonia. Our data further revealed that increased expression of pro-fusion factor MFN1 upregulated mitochondrial metabolism, whereas DRP1 specifically regulated mitochondrial permeability transition pore opening in differentiating spermatogonia. Taken together, our findings unveil how proper spermatogonial differentiation is precisely controlled by concurrently accelerated and properly balanced mitochondrial fusion and fission in a germ cell stage-specific manner, thereby providing critical insights about mitochondrial contribution to stem cell fate decision.","PeriodicalId":21885,"journal":{"name":"Stem Cell Reports","volume":" ","pages":"1548-1563"},"PeriodicalIF":5.9,"publicationDate":"2024-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11589200/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142406811","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

Breaking the burst: Unveiling mechanisms behind fragmented network bursts in patient-derived neurons. 打破爆发：揭示患者神经元碎片化网络爆发背后的机制

IF 5.9 2区医学

Stem Cell Reports Pub Date : 2024-11-12 Epub Date: 2024-10-03 DOI: 10.1016/j.stemcr.2024.09.001

Nina Doorn, Eva J H F Voogd, Marloes R Levers, Michel J A M van Putten, Monica Frega

{"title":"Breaking the burst: Unveiling mechanisms behind fragmented network bursts in patient-derived neurons.","authors":"Nina Doorn, Eva J H F Voogd, Marloes R Levers, Michel J A M van Putten, Monica Frega","doi":"10.1016/j.stemcr.2024.09.001","DOIUrl":"10.1016/j.stemcr.2024.09.001","url":null,"abstract":"Fragmented network bursts (NBs) are observed as a phenotypic driver in many patient-derived neuronal networks on multi-electrode arrays (MEAs), but the pathophysiological mechanisms underlying this phenomenon are unknown. Here, we used our previously developed biophysically detailed in silico model to investigate these mechanisms. Fragmentation of NBs in our model simulations occurred only when the level of short-term synaptic depression (STD) was enhanced, suggesting that STD is a key player. Experimental validation with Dynasore, an STD enhancer, induced fragmented NBs in healthy neuronal networks in vitro. Additionally, we showed that strong asynchronous neurotransmitter release, NMDA currents, or short-term facilitation (STF) can support the emergence of multiple fragments in NBs by producing excitation that persists after high-frequency firing stops. Our results provide important insights into disease mechanisms and potential pharmaceutical targets for neurological disorders modeled using human induced pluripotent stem cell (hiPSC)-derived neurons.","PeriodicalId":21885,"journal":{"name":"Stem Cell Reports","volume":" ","pages":"1583-1597"},"PeriodicalIF":5.9,"publicationDate":"2024-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11589196/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142376045","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