Stem Cell Reports最新文献

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":"","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":"","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

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

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":"","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":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

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

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":"","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":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

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":"","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":"","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

引用次数: 0

Neural crest precursors from the skin are the primary source of directly reprogrammed neurons. 来自皮肤的神经嵴前体是直接重编程神经元的主要来源。

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.2024.10.003

Justin J Belair-Hickey, Ahmed Fahmy, Wenbo Zhang, Rifat S Sajid, Brenda L K Coles, Michael W Salter, Derek van der Kooy

引用次数: 0

Lineage-specific dynamics of loss of X upregulation during inactive-X reactivation. 无活性-X 再激活过程中 X 缺失上调的特定系动态。

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.2024.10.001

Hemant Chandru Naik, Deepshikha Chandel, Sudeshna Majumdar, Maniteja Arava, Runumi Baro, Harshavardhan Bv, Kishore Hari, Parichitran Ayyamperumal, Avinchal Manhas, Mohit Kumar Jolly, Srimonta Gayen

{"title":"Lineage-specific dynamics of loss of X upregulation during inactive-X reactivation.","authors":"Hemant Chandru Naik, Deepshikha Chandel, Sudeshna Majumdar, Maniteja Arava, Runumi Baro, Harshavardhan Bv, Kishore Hari, Parichitran Ayyamperumal, Avinchal Manhas, Mohit Kumar Jolly, Srimonta Gayen","doi":"10.1016/j.stemcr.2024.10.001","DOIUrl":"10.1016/j.stemcr.2024.10.001","url":null,"abstract":"In mammals, X chromosome dosage is balanced between sexes through the silencing of one X chromosome in females. Recent single-cell RNA sequencing analysis demonstrated that the inactivation of the X chromosome is accompanied by the upregulation of the active X chromosome (Xa) during mouse embryogenesis. Here, we have investigated if the reactivation of inactive-X (Xi) leads to the loss of Xa upregulation in different cellular or developmental contexts. We find that while Xi reactivation and loss of Xa upregulation are tightly coupled in mouse embryonic epiblast and induced pluripotent stem cells, that is not the case in germ cells. Moreover, we demonstrate that partial reactivation of Xi in mouse extra-embryonic endoderm stem cells and human B cells does not result in the loss of Xa upregulation. Finally, we have established a mathematical model for the transcriptional coordination of two X chromosomes. Together, we conclude that the reactivation of Xi is not always synchronized with the loss of Xa upregulation.","PeriodicalId":21885,"journal":{"name":"Stem Cell Reports","volume":" ","pages":"1564-1582"},"PeriodicalIF":5.9,"publicationDate":"2024-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142565072","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