Stem Cell Reports最新文献_第3页

Single-cell transcriptome and surfaceome profiling of the adult human retinal pigment epithelium. 成人视网膜色素上皮单细胞转录组和表面组分析。

IF 5.1 2区医学

Stem Cell Reports Pub Date : 2025-09-09 Epub Date: 2025-08-28 DOI: 10.1016/j.stemcr.2025.102611

Farhad Farjood, Swapna Nandakumar, Taylor Bertucci, Thomas Kiehl, Steve Lotz, Yue Wang, Jacob Black, Skanda Sai, Jade Kozak, Brigitte L Arduini, Sally Temple, Nathan C Boles, Jeffrey H Stern

{"title":"Single-cell transcriptome and surfaceome profiling of the adult human retinal pigment epithelium.","authors":"Farhad Farjood, Swapna Nandakumar, Taylor Bertucci, Thomas Kiehl, Steve Lotz, Yue Wang, Jacob Black, Skanda Sai, Jade Kozak, Brigitte L Arduini, Sally Temple, Nathan C Boles, Jeffrey H Stern","doi":"10.1016/j.stemcr.2025.102611","DOIUrl":"10.1016/j.stemcr.2025.102611","url":null,"abstract":"The retinal pigment epithelium (RPE) is a pigmented monolayer of cells beneath the neural retina that supports photoreceptor cell function essential for vision. Our study explores the diversity of adult human RPE subpopulations and associated implications for retinal biology. Employing cellular indexing of transcriptomes and epitopes by sequencing (CITE-seq), we identified distinct RPE cell subpopulations characterized by unique single-cell transcriptomic and surface protein signatures. Immunohistochemical analysis using CITE-seq markers demonstrated that different RPE subpopulations had previously unappreciated spatial patterns. Enrichment by CITE-seq surface marker selection revealed that different RPE subpopulations have distinct functions. By comparing native RPE cells isolated from the adult RPE layer to cultured RPE cells, we demonstrated that most RPE subpopulations were preserved during culture, a finding with relevance to an RPE cell product currently in clinical trial for treatment of non-exudative age-related macular degeneration. These findings deepen understanding of human RPE biology and provide valuable insights to optimize RPE-cell-based therapy.","PeriodicalId":21885,"journal":{"name":"Stem Cell Reports","volume":" ","pages":"102611"},"PeriodicalIF":5.1,"publicationDate":"2025-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12447320/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144969699","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 disrupts intracellular trafficking and iron homeostasis in a reproducible iPSC-based model of human brain endothelial cells. ApoE4在可复制的基于ipsc的人脑内皮细胞模型中破坏细胞内运输和铁稳态。

IF 5.1 2区医学

Stem Cell Reports Pub Date : 2025-09-09 Epub Date: 2025-08-21 DOI: 10.1016/j.stemcr.2025.102607

Luisa Bell, Shane Clerkin, Sila Rizalar, Antoine Rizkallah, Nadine Stokar-Regenscheit, Xandor M Spijkers, Nienke R Wevers, Claire Simonneau, Angélique Augustin, Barbara Höllbacher, Lia D'Abate, Joanna Ficek-Pascual, Kim Schneider, Desiree Von Tell, Thomas Maurissen, Chiara Zanini, Christelle Zundel, Sabrina Golling, Christine Becker, Alex Odermatt, Lynette C Foo, Martina Pigoni, Roberto Villaseñor

{"title":"ApoE4 disrupts intracellular trafficking and iron homeostasis in a reproducible iPSC-based model of human brain endothelial cells.","authors":"Luisa Bell, Shane Clerkin, Sila Rizalar, Antoine Rizkallah, Nadine Stokar-Regenscheit, Xandor M Spijkers, Nienke R Wevers, Claire Simonneau, Angélique Augustin, Barbara Höllbacher, Lia D'Abate, Joanna Ficek-Pascual, Kim Schneider, Desiree Von Tell, Thomas Maurissen, Chiara Zanini, Christelle Zundel, Sabrina Golling, Christine Becker, Alex Odermatt, Lynette C Foo, Martina Pigoni, Roberto Villaseñor","doi":"10.1016/j.stemcr.2025.102607","DOIUrl":"10.1016/j.stemcr.2025.102607","url":null,"abstract":"Transferrin receptor in brain endothelial cells can deliver therapeutic antibodies to the brain via transcytosis across the blood-brain barrier (BBB). Whether receptor transport remains intact in Alzheimer disease is still a major open question. Here, we investigated whether apolipoprotein E4 (ApoE4), the major genetic risk factor for Alzheimer disease, altered intracellular transport in human brain endothelial cells. To achieve this, we first developed a reproducible protocol for induced pluripotent stem cells based on a defined chemical cocktail and extracellular matrix support to differentiate brain endothelial cells (iCE-BECs). Multi-omics profiling and functional transport assays showed that iCE-BECs have a brain endothelial gene signature and recapitulate receptor-mediated transcytosis of a clinically validated Brainshuttle antibody against transferrin receptor. Engineered iCE-BECs homozygous for ApoE4 had impaired endosome maturation, increased transferrin receptor expression, and reduced cytoplasmic iron. Our data revealed that ApoE4 can impact intracellular transport and iron homeostasis at the BBB in a cell-autonomous manner.","PeriodicalId":21885,"journal":{"name":"Stem Cell Reports","volume":" ","pages":"102607"},"PeriodicalIF":5.1,"publicationDate":"2025-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12447338/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144969779","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

Suppressing Nodal Signaling Activity Predisposes Ectodermal Differentiation of Epiblast Stem Cells. 抑制节点信号活动有助于外胚层干细胞的外胚层分化。

IF 5.1 2区医学

Stem Cell Reports Pub Date : 2025-09-09 Epub Date: 2025-08-05 DOI: 10.1016/j.stemcr.2025.102609

Chang Liu, Ran Wang, Zhisong He, Pierre Osteil, Emilie Wilkie, Xianfa Yang, Jun Chen, Guizhong Cui, Wenke Guo, Yingying Chen, Guangdun Peng, Patrick P L Tam, Naihe Jing

引用次数: 0

Pen-2 regulates glial homeostasis by coordinating self-renewal and transdifferentiation programs in oligodendrocyte precursor cells. Pen-2通过协调少突胶质前体细胞的自我更新和转分化程序来调节胶质稳态。

IF 5.1 2区医学

Stem Cell Reports Pub Date : 2025-09-09 Epub Date: 2025-08-28 DOI: 10.1016/j.stemcr.2025.102612

Huiru Bi, Jinxing Hou, Wenkai Shao, Chenyi Ge, Yang Liu, Runmin Wang, Guiquan Chen, Yun Xu, Zhiye Wang

{"title":"Pen-2 regulates glial homeostasis by coordinating self-renewal and transdifferentiation programs in oligodendrocyte precursor cells.","authors":"Huiru Bi, Jinxing Hou, Wenkai Shao, Chenyi Ge, Yang Liu, Runmin Wang, Guiquan Chen, Yun Xu, Zhiye Wang","doi":"10.1016/j.stemcr.2025.102612","DOIUrl":"10.1016/j.stemcr.2025.102612","url":null,"abstract":"Presenilin enhancer 2 (Pen-2) is implicated in neurological diseases characterized by glial dysregulation. To investigate whether oligodendrocytic γ-secretase activity is important for the maintenance of glial populations, we analyzed two conditional knockout (cKO) mouse models lacking Pen-2 or nicastrin. Both models exhibited similar expansions of oligodendrocyte precursor cells (OPCs) and astrocytes in the CNS. To test whether STAT3 mediates Pen-2-dependent glial homeostasis, we inactivated Stat3 in Pen-2 cKO mice. Intriguingly, STAT3 deficiency did not attenuate OPC expansion but normalized astrocyte numbers. We further demonstrated that Pen-2 represses Ascl1 expression via HES1 and that Ascl1 knockdown rescues the aberrant self-renewal capacity of Pen-2-deficient OPCs. Collectively, these results uncover a dual regulatory mechanism by which Pen-2 maintains glial homeostasis by (1) restraining OPC self-renewal through the HES1-ASCL1 axis and (2) suppressing OPC-to-astrocyte transdifferentiation in a STAT3-dependent manner. Our findings provide novel insights into glial abnormalities in PEN-2-linked neurological diseases.","PeriodicalId":21885,"journal":{"name":"Stem Cell Reports","volume":" ","pages":"102612"},"PeriodicalIF":5.1,"publicationDate":"2025-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12447332/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144969523","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 emergence of electrical activity in human brain organoids. 人脑类器官电活动的出现。

IF 5.1 2区医学

Stem Cell Reports Pub Date : 2025-09-09 DOI: 10.1016/j.stemcr.2025.102632

Sara Mancinelli, Sebastiano Bariselli, Simona Lodato

引用次数: 0

Transparency and ongoing communication with participants in brain organoid research: Consensus of an interdisciplinary working group. 类脑器官研究的透明度和与参与者的持续沟通：跨学科工作组的共识。

IF 5.1 2区医学

Stem Cell Reports Pub Date : 2025-09-09 Epub Date: 2025-06-26 DOI: 10.1016/j.stemcr.2025.102546

Betty Cohn, Megan Doerr, Pamela Feliciano, Stephanie M Fullerton, Saskia Hendriks, Soren Holm, Insoo Hyun, Karin Jongsma, Karen M Meagher, M Elizabeth Ross, Jason L Stein, Sharon F Terry, Katherine E MacDuffie

引用次数: 0

Ectopic recruitment of neuroblasts in striatal myelin bundles and nucleus accumbens following AraC chemical lesion. AraC化学损伤后纹状体髓鞘束和伏隔核神经母细胞异位募集。

IF 5.1 2区医学

Stem Cell Reports Pub Date : 2025-09-09 DOI: 10.1016/j.stemcr.2025.102636

Irini Thanou, Paraskevi N Koutsoudaki, Maria Margariti, Federico Luzzati, Sophia Havaki, Vassilis G Gorgoulis, Dimitra Thomaidou

{"title":"Ectopic recruitment of neuroblasts in striatal myelin bundles and nucleus accumbens following AraC chemical lesion.","authors":"Irini Thanou, Paraskevi N Koutsoudaki, Maria Margariti, Federico Luzzati, Sophia Havaki, Vassilis G Gorgoulis, Dimitra Thomaidou","doi":"10.1016/j.stemcr.2025.102636","DOIUrl":"10.1016/j.stemcr.2025.102636","url":null,"abstract":"In the adult brain, neural stem cells (NSCs) constitutively generate new neurons in specific neurogenic domains. Recent research has unveiled reactive neurogenesis, whereby brain injury triggers NSC activation, enhancing their differentiation potential and guiding progeny to injured areas. Our study provides evidence of alternative migration pathways for newborn neurons in the mouse subcortical forebrain, revealed by administration of a chemotherapeutic agent. This allows a high number of newborn neurons to migrate long distances over an extended period. Notably, a subpopulation of neuroblasts diverts from the canonical SVZ-olfactory bulb (OB) rostral migratory stream toward the striatum (STR), with distinct localization along striatal myelin tracts and through nucleus accumbens (NAc) to the anterior commissure (AC). This neuroblast (NB) rerouting is accompanied by with oligodendrocyte lineage dysregulation and myelin deficits, suggesting a link between ectopic NB presence and observed myelin abnormalities.","PeriodicalId":21885,"journal":{"name":"Stem Cell Reports","volume":"20 9","pages":"102636"},"PeriodicalIF":5.1,"publicationDate":"2025-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12447329/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145034151","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

Germline transmission of cryopreserved mouse spermatogonial stem cells maintained on the International Space Station. 在国际空间站上保存的冷冻小鼠精原干细胞的种系传播。

IF 5.1 2区医学

Stem Cell Reports Pub Date : 2025-09-09 Epub Date: 2025-08-14 DOI: 10.1016/j.stemcr.2025.102602

Mito Kanatsu-Shinohara, Takuya Yamamoto, Yusuke Shiromoto, Hiroko Morimoto, Tianjiao Liu, Tohru Yamamori, Tomokazu Yamasaki, Takashi Shinohara

{"title":"Germline transmission of cryopreserved mouse spermatogonial stem cells maintained on the International Space Station.","authors":"Mito Kanatsu-Shinohara, Takuya Yamamoto, Yusuke Shiromoto, Hiroko Morimoto, Tianjiao Liu, Tohru Yamamori, Tomokazu Yamasaki, Takashi Shinohara","doi":"10.1016/j.stemcr.2025.102602","DOIUrl":"10.1016/j.stemcr.2025.102602","url":null,"abstract":"Despite growing interest in space exploration, the effects of spaceflight on stem cells remain largely unknown. Damages to germline cells are especially crucial, as spaceflight poses risks to gametogenesis, with abnormalities observed in multiple species. While embryonic stem (ES) cells show genomic instability after space exposure and have not yet produced offspring, this study demonstrates successful offspring production from cryopreserved mouse spermatogonial stem cells (SSCs) stored on the International Space Station for 6 months. Spaceflight did not increase apoptosis or DNA damage in SSCs. After thawing, SSCs proliferated comparably to those cryopreserved on Earth, showing no significant phenotypic or functional differences. Offspring were produced via spermatogonial transplantation followed by natural mating. Since SSCs from many species can be cryopreserved like somatic cells and still produce sperm, they offer a promising resource for germline preservation during space exploration.","PeriodicalId":21885,"journal":{"name":"Stem Cell Reports","volume":" ","pages":"102602"},"PeriodicalIF":5.1,"publicationDate":"2025-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12447337/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144859617","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

Thymosin beta 4 as an Alzheimer disease intervention target identified using human brain organoids. 胸腺酶β 4作为阿尔茨海默病的干预靶点，利用人脑类器官鉴定。

IF 5.1 2区医学

Stem Cell Reports Pub Date : 2025-09-09 Epub Date: 2025-08-14 DOI: 10.1016/j.stemcr.2025.102601

Peng-Ming Zeng, Xin-Yao Sun, Yang Li, Wen-di Wu, Jing Huang, Dong-Dong Cao, Pin-Jue Qian, Xiang-Chun Ju, Zhen-Ge Luo

{"title":"Thymosin beta 4 as an Alzheimer disease intervention target identified using human brain organoids.","authors":"Peng-Ming Zeng, Xin-Yao Sun, Yang Li, Wen-di Wu, Jing Huang, Dong-Dong Cao, Pin-Jue Qian, Xiang-Chun Ju, Zhen-Ge Luo","doi":"10.1016/j.stemcr.2025.102601","DOIUrl":"10.1016/j.stemcr.2025.102601","url":null,"abstract":"The developmental origin of Alzheimer disease (AD) has been proposed but is arguably debated. Here, we developed cerebral organoids from induced pluripotent stem cells (iPSCs) with mutations in amyloid precursor protein (APP) associated with familial AD (fAD) and analyzed the dynamic changes of cellular states. We found that mature neurons induced in fAD organoids markedly decreased compared to that of health control, accompanied with increased cell senescence and β-amyloid (Aβ) production. Interestingly, the expression level of the gene TMSB4X that encodes thymosin beta 4 (Tβ4) significantly decreased both in fAD organoids' neurons and AD patients' excitatory neurons. Remarkably, the neurodevelopmental deficits and Aβ formation in fAD organoids were rescued by treatment with Tβ4. The beneficial effects of Tβ4 were also revealed in 5xfAD model mice. Thus, this study has identified Tβ4 as a neuroprotective factor that may mitigate altered neurogenesis and AD pathology, highlighting a potential for disease intervention.","PeriodicalId":21885,"journal":{"name":"Stem Cell Reports","volume":" ","pages":"102601"},"PeriodicalIF":5.1,"publicationDate":"2025-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12447315/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144859618","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

Inhibition of N-myristoyltransferase in pluripotent stem cells promotes the naive state in mice and elicits trophectoderm and primitive endoderm markers in humans. 在多能干细胞中抑制n -肉豆蔻酰基转移酶可促进小鼠的初始状态，并在人类中诱导滋养外胚层和原始内胚层标记物。

IF 5.1 2区医学

Stem Cell Reports Pub Date : 2025-09-09 Epub Date: 2025-08-28 DOI: 10.1016/j.stemcr.2025.102610

Junko Yoshida, Hitomi Watanabe, Kaori Yamauchi, Takumi Nishikubo, Ayako Isotani, Satoshi Ohtsuka, Hitoshi Niwa, Yuki Kawamoto, Hidenori Akutsu, Akihiro Umezawa, Hirofumi Suemori, Yasuhiro Takashima, Hideo Matsuda, Gen Kondoh, Junji Takeda, Kyoji Horie

{"title":"Inhibition of N-myristoyltransferase in pluripotent stem cells promotes the naive state in mice and elicits trophectoderm and primitive endoderm markers in humans.","authors":"Junko Yoshida, Hitomi Watanabe, Kaori Yamauchi, Takumi Nishikubo, Ayako Isotani, Satoshi Ohtsuka, Hitoshi Niwa, Yuki Kawamoto, Hidenori Akutsu, Akihiro Umezawa, Hirofumi Suemori, Yasuhiro Takashima, Hideo Matsuda, Gen Kondoh, Junji Takeda, Kyoji Horie","doi":"10.1016/j.stemcr.2025.102610","DOIUrl":"10.1016/j.stemcr.2025.102610","url":null,"abstract":"Naive and primed states represent distinct phases of pluripotency during early embryonic development, both of which can be captured and interconverted in vitro. To understand pluripotency regulation, we performed a recessive genetic screen using homozygous mutant mouse embryonic stem cells (mESCs) and identified N-myristoyltransferase (NMT) as a novel regulator. Disruption of Nmt1 in mESCs conferred resistance to differentiation, and NMT suppression in mouse epiblast stem cells (mEpiSCs) promoted the conversion from the primed to the naive state. This effect was independent of proto-oncogene tyrosine-protein kinase Src (SRC), which is a major substrate of NMT and is known to promote mESC differentiation. In contrast, NMT suppression in naive-state human induced pluripotent stem cells (hiPSCs) partially induced naive markers but, more notably, expanded subpopulations expressing trophectoderm and primitive endoderm markers, most of which co-expressed the pluripotency marker POU5F1. These results identify NMT as a novel regulator of pluripotency, with distinct roles in mice and humans.","PeriodicalId":21885,"journal":{"name":"Stem Cell Reports","volume":" ","pages":"102610"},"PeriodicalIF":5.1,"publicationDate":"2025-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12447342/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144969763","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