Stem Cell Reports最新文献_第3页

Revisiting patient protection in unproven cell and gene therapies under Japan's safety act. 根据日本安全法，重新审视未经证实的细胞和基因疗法对患者的保护。

IF 5.6 2区医学

Stem Cell Reports Pub Date : 2026-10-13 Epub Date: 2026-09-03 DOI: 10.1016/j.stemcr.2026.103077

Kayo Takashima, Michael Morrison, Andrew J T George, Jusaku Minari

引用次数: 0

Insulin receptor substrate 2 regulates placental syncytiotrophoblast differentiation at the maternal-fetal interface. 胰岛素受体底物2在母胎界面调节胎盘合胞滋养细胞分化。

IF 5.6 2区医学

Stem Cell Reports Pub Date : 2026-10-13 Epub Date: 2026-09-03 DOI: 10.1016/j.stemcr.2026.103061

Johanna Grinat, María Moya-Navamuel, Paula Blanco-Cueto, Claudia Alemán-Juanes, Nathaly Hernández-Díaz, Maravillas Mellado-López, Amparo Galán, Luke A Noon, Deborah J Burks, Katrien De Clercq, Jorge López-Tello, Vicente Pérez-García

{"title":"Insulin receptor substrate 2 regulates placental syncytiotrophoblast differentiation at the maternal-fetal interface.","authors":"Johanna Grinat, María Moya-Navamuel, Paula Blanco-Cueto, Claudia Alemán-Juanes, Nathaly Hernández-Díaz, Maravillas Mellado-López, Amparo Galán, Luke A Noon, Deborah J Burks, Katrien De Clercq, Jorge López-Tello, Vicente Pérez-García","doi":"10.1016/j.stemcr.2026.103061","DOIUrl":"10.1016/j.stemcr.2026.103061","url":null,"abstract":"The placental labyrinth is the primary site of maternal-fetal exchange, and its disruption contributes to placental insufficiency and fetal growth restriction (FGR). Here, we identify insulin receptor substrate 2 (IRS2) as a key regulator of mouse placental labyrinth development. Irs2 is expressed in the syncytiotrophoblast (SynT) layers of the labyrinth, where it integrates growth factor signaling during placental morphogenesis. Loss of IRS2 disrupts labyrinth organization, causing defective SynT-II differentiation, impaired trophoblast fusion, and reduced fetal vascularization. Using CRISPR-Cas9-engineered Irs2-/- trophoblast stem cells, we show that IRS2 deficiency impairs upregulation of the SynT-II regulators Pparγ and Gcm1, disrupting SynT-II differentiation and sinusoidal trophoblast giant cell specification. Mechanistically, IRS2 relays insulin-like growth factor (IGF) signals through phosphatidylinositol 3-kinase (PI3K)/AKT and mitogen-activated protein kinase (MAPK) pathways to coordinate trophoblast proliferation, differentiation, and vascular morphogenesis. Human trophoblast stem cell differentiation and organoid analyses reveal IRS2 enrichment in the human syncytiotrophoblast (STB), indicating conserved expression at the human maternal-fetal interface.","PeriodicalId":21885,"journal":{"name":"Stem Cell Reports","volume":" ","pages":"103061"},"PeriodicalIF":5.6,"publicationDate":"2026-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148888660","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

SIRT1 promotes endothelial activity and osteogenesis in vitro and ameliorates age-related skeletal regeneration defects in vivo. SIRT1在体外促进内皮活性和成骨，并在体内改善与年龄相关的骨骼再生缺陷。

IF 5.6 2区医学

Stem Cell Reports Pub Date : 2026-10-13 Epub Date: 2026-09-03 DOI: 10.1016/j.stemcr.2026.103063

Shibo Liu, Jingjing Shao, Qiheng Yang, Hanghang Liu, Yao Liu, Zizhuo Zheng, En Luo

{"title":"SIRT1 promotes endothelial activity and osteogenesis in vitro and ameliorates age-related skeletal regeneration defects in vivo.","authors":"Shibo Liu, Jingjing Shao, Qiheng Yang, Hanghang Liu, Yao Liu, Zizhuo Zheng, En Luo","doi":"10.1016/j.stemcr.2026.103063","DOIUrl":"10.1016/j.stemcr.2026.103063","url":null,"abstract":"Understanding age-driven bone weakening mechanisms is essential for developing precision therapeutic strategies. This study systematically investigated skeletal aging, focusing on the critical decline of SIRT1 and its impact on type H vessels and osteogenic cells. We found that SIRT1 markedly enhanced both endothelial tube formation and osteogenic differentiation in senescent bone marrow-derived mesenchymal stem cell (BMSC)/human umbilical vein endothelial cell (HUVEC) co-cultures. In vivo validation studies revealed that pharmacological activation of SIRT1 significantly improved bone regeneration in age-related osteoporotic defects in both femoral and mandibular sites. Mechanistically, β-catenin served as a downstream mediator of these effects in our experimental systems, with SIRT1 promoting β-catenin deacetylation and nuclear translocation to activate Wnt signaling. By demonstrating that SIRT1 enhances both endothelial and osteogenic functions in the aged bone microenvironment, this work provides a rationale for targeted bone rejuvenation strategies and mechanistically informed therapeutic innovation against geriatric osteoporosis.","PeriodicalId":21885,"journal":{"name":"Stem Cell Reports","volume":" ","pages":"103063"},"PeriodicalIF":5.6,"publicationDate":"2026-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148887189","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

Directing GABAergic neuronal identity from human iPSCs through developmental patterning. 通过发育模式引导人多能干细胞的gaba能神经元身份。

IF 5.6 2区医学

Stem Cell Reports Pub Date : 2026-10-13 Epub Date: 2026-09-24 DOI: 10.1016/j.stemcr.2026.103086

Ruiqi Hu, Linda L Boshans, Yiran Tao, Bohan Zhu, Junlong Li, Xindi Li, Rui Dang, Marianna Liang, Peiwen Cai, Mark Youssef, Gizem Inak, Yingnan Song, Xuran Wang, Alexander M Tsankov, Joseph D Buxbaum, Peng Jiang, Zhiping P Pang, Sai Ma, Nan Yang

{"title":"Directing GABAergic neuronal identity from human iPSCs through developmental patterning.","authors":"Ruiqi Hu, Linda L Boshans, Yiran Tao, Bohan Zhu, Junlong Li, Xindi Li, Rui Dang, Marianna Liang, Peiwen Cai, Mark Youssef, Gizem Inak, Yingnan Song, Xuran Wang, Alexander M Tsankov, Joseph D Buxbaum, Peng Jiang, Zhiping P Pang, Sai Ma, Nan Yang","doi":"10.1016/j.stemcr.2026.103086","DOIUrl":"10.1016/j.stemcr.2026.103086","url":null,"abstract":"GABAergic interneurons are implicated in numerous neurodevelopmental and neuropsychiatric disorders. Transcription factor (TF)-mediated induction of human pluripotent stem cells (PSCs) rapidly generates GABAergic neurons, yet their regional identity remains poorly defined. Here, we show that the chromatin state of the starting population constrains the neuronal identities specified by ASCL1 and DLX2. Brief neural patterning via dual-SMAD and WNT inhibition prior to TF induction biases PSCs toward GABAergic neurons with forebrain-associated identities, whereas TF induction of PSCs yields neurons with broader regional signatures, including hypothalamic and thalamic programs. Benchmarking multiple approaches against a human fetal brain atlas reveals distinct regional identity biases and disease gene enrichment profiles across methods, providing a framework for selecting differentiation strategies for disease modeling. Applying this approach to ADNP syndrome, we demonstrate that the recurrent p.Tyr719∗ mutation disrupts interneuron maturation and subtype-associated transcriptional programs and impairs inhibitory synaptic transmission in human GABAergic neurons.","PeriodicalId":21885,"journal":{"name":"Stem Cell Reports","volume":" ","pages":"103086"},"PeriodicalIF":5.6,"publicationDate":"2026-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149040607","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

Balancing flexibility and ethical oversight: Japan's regulatory framework for human stem cell-based embryo model research. 平衡灵活性和伦理监督：日本对人类干细胞胚胎模型研究的监管框架。

IF 5.6 2区医学

Stem Cell Reports Pub Date : 2026-10-13 Epub Date: 2026-09-24 DOI: 10.1016/j.stemcr.2026.103085

Ayako Kamisato, Hidenori Akutsu

引用次数: 0

Lysine-specific demethylase 1 links metabolism to stemness in human neural stem cells. 赖氨酸特异性去甲基酶1将人类神经干细胞的代谢与干细胞性联系起来。

IF 5.6 2区医学

Stem Cell Reports Pub Date : 2026-10-08 DOI: 10.1016/j.stemcr.2026.103115

Kazutoshi Murotomi, Kazumi Hirano, Kazutaka Araki, Hiroko Ishitsuka, Daisuke Miura, Shinjiro Hino, Masakazu Namihira

{"title":"Lysine-specific demethylase 1 links metabolism to stemness in human neural stem cells.","authors":"Kazutoshi Murotomi, Kazumi Hirano, Kazutaka Araki, Hiroko Ishitsuka, Daisuke Miura, Shinjiro Hino, Masakazu Namihira","doi":"10.1016/j.stemcr.2026.103115","DOIUrl":"https://doi.org/10.1016/j.stemcr.2026.103115","url":null,"abstract":"Epigenetic regulation of stem cell fate requires tight coordination with cellular metabolism; however, key downstream effectors remain poorly defined. Here, we show that lysine-specific demethylase 1 (LSD1) governs metabolic programs essential for stemness in human fetal neural stem cells. LSD1 inhibition induced a pronounced glycolytic shift accompanied by altered lineage commitment, characterized by suppression of neuronal differentiation and promotion of astrocytic fate. Machine learning-based Elastic Net analysis of transcriptomic data identified a subset of metabolic genes, including PLPP2 and CPT1A, which regulate phospholipid metabolism and mitochondrial fatty acid oxidation, as key downstream effectors of LSD1. Functional perturbation experiments showed that knockdown of these candidates attenuated LSD1 inhibition-induced glycolytic activation and ameliorated distinct differentiation phenotypes. Chromatin immunoprecipitation sequencing revealed LSD1 occupancy at metabolic gene loci, supporting their transcriptional repression by LSD1. Together, these findings identify LSD1 as an epigenetic gatekeeper preserving stemness by restraining glycolysis and inappropriate lineage commitment.","PeriodicalId":21885,"journal":{"name":"Stem Cell Reports","volume":" ","pages":"103115"},"PeriodicalIF":5.6,"publicationDate":"2026-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149138356","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

Characterization of structural variants in KOLF2.1J iPSCs and their potential impact on forebrain organoid differentiation. KOLF2.1J iPSCs结构变异的特征及其对前脑类器官分化的潜在影响

IF 5.6 2区医学

Stem Cell Reports Pub Date : 2026-10-08 DOI: 10.1016/j.stemcr.2026.103112

Lízia Branco, Zeynep Yentür, Madison James Yang, Parithi Balachandran, Kamilla Sedov, G Kumar, Faria Zafar, Theresa Kagermeier, Kseniia Sarieva, Katharina Becker, William C Skarnes, Birgitt Schüle, Simone Mayer, Christine R Beck

{"title":"Characterization of structural variants in KOLF2.1J iPSCs and their potential impact on forebrain organoid differentiation.","authors":"Lízia Branco, Zeynep Yentür, Madison James Yang, Parithi Balachandran, Kamilla Sedov, G Kumar, Faria Zafar, Theresa Kagermeier, Kseniia Sarieva, Katharina Becker, William C Skarnes, Birgitt Schüle, Simone Mayer, Christine R Beck","doi":"10.1016/j.stemcr.2026.103112","DOIUrl":"https://doi.org/10.1016/j.stemcr.2026.103112","url":null,"abstract":"The KOLF2.1J human induced pluripotent stem cell (iPSC) line was created as a reference for neurological disease modeling. Previous genotyping efforts identified several large structural variants (SVs), raising questions about their potential impact on neuronal differentiation. Here, we identified 37 additional SVs using long-read sequencing and optical genome mapping. Additionally, we found that one of the known SVs contained a previously undetected overlap with RYBP, a neurodevelopmental gene. To assess the functional consequences of these SVs, we performed single-cell RNA sequencing of day 90 forebrain organoids derived from KOLF2.1J and two independent control iPSC lines. While cell-type composition was preserved, multiple SV-affected genes were differentially expressed and cell-cell adhesion and synapse-related processes were enriched in KOLF2.1J organoids. These findings highlight the importance of robust genetic characterization and multi-line validation for reliable iPSC-based modeling.","PeriodicalId":21885,"journal":{"name":"Stem Cell Reports","volume":" ","pages":"103112"},"PeriodicalIF":5.6,"publicationDate":"2026-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149138415","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

Human spinal cord organoids recapitulate developmental and disease-associated oligodendrocyte lineage signatures. 人类脊髓类器官概括了发育和疾病相关的少突胶质细胞谱系特征。

IF 5.6 2区医学

Stem Cell Reports Pub Date : 2026-10-08 DOI: 10.1016/j.stemcr.2026.103114

Taylor Pio, Meghna Bettaiah, Ruizi Zhao, Supriya S Wariyar, Sabra Mouhi, Emily J Hill, Steven A Sloan, Jimena Andersen

{"title":"Human spinal cord organoids recapitulate developmental and disease-associated oligodendrocyte lineage signatures.","authors":"Taylor Pio, Meghna Bettaiah, Ruizi Zhao, Supriya S Wariyar, Sabra Mouhi, Emily J Hill, Steven A Sloan, Jimena Andersen","doi":"10.1016/j.stemcr.2026.103114","DOIUrl":"10.1016/j.stemcr.2026.103114","url":null,"abstract":"Oligodendrocytes play essential roles in central nervous system development and homeostasis, and their dysfunction is a hallmark of numerous neurological disorders. However, human in vitro systems that support oligodendrocyte lineage progression while enabling the study of disease-relevant states remain limited. Here, we establish human spinal cord organoids (hSpO) and cortico-motor assembloids as platforms to model oligodendrocyte development, neuron-glia interactions, and cytokine-induced dysfunction. We show that hSpO generate oligodendrocyte lineage populations that transcriptionally resemble the developing human spinal cord, and oligodendrocyte progenitor cells (OPCs) that exhibit physiologically relevant behaviors, including migration and monosynaptic neuronal input. Exposure of assembloids to pro-inflammatory cytokines induces transcriptional changes across the oligodendrocyte lineage, characterized by altered lineage progression and acquisition of disease-associated gene expression programs that mirror signatures observed in tissues from patients with multiple sclerosis (MS). Together, this work establishes hSpO and assembloids as in vitro systems for studying oligodendrocyte lineage development and disease-associated states in a human multicellular context.","PeriodicalId":21885,"journal":{"name":"Stem Cell Reports","volume":" ","pages":"103114"},"PeriodicalIF":5.6,"publicationDate":"2026-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149138403","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

Bone marrow-inspired DLL1-presenting microparticles enhance asymmetric division and maintenance of mouse hematopoietic stem and progenitor cells. 骨髓激发的dll1提呈微粒增强小鼠造血干细胞和祖细胞的不对称分裂和维持。

IF 5.6 2区医学

Stem Cell Reports Pub Date : 2026-09-08 Epub Date: 2026-08-27 DOI: 10.1016/j.stemcr.2026.103059

Li Wenjing, Feng Yiting, Han Dongbo, Ao Yanxiao, Michael W Chen, Li Ning, Jin Yuhong, Liang Haiwei, Liu Wen, Zhu Xiaoyu, Du Yanan

{"title":"Bone marrow-inspired DLL1-presenting microparticles enhance asymmetric division and maintenance of mouse hematopoietic stem and progenitor cells.","authors":"Li Wenjing, Feng Yiting, Han Dongbo, Ao Yanxiao, Michael W Chen, Li Ning, Jin Yuhong, Liang Haiwei, Liu Wen, Zhu Xiaoyu, Du Yanan","doi":"10.1016/j.stemcr.2026.103059","DOIUrl":"10.1016/j.stemcr.2026.103059","url":null,"abstract":"Understanding the regulation of hematopoietic stem and progenitor cell (HSPC) fate and translating it into effective culture strategies remains a significant challenge. Asymmetric lysosomal inheritance during HSPC division has been shown to predict variations in daughter cell activity and fate, yet the underlying regulators remain unclear. Through cell-cell communication analysis of bone marrow single-cell sequencing data, we identified the Notch ligand Delta-like protein 1 (DLL1) as a potential regulator in HSPC asymmetric division (ACD). Interactions between DLL1-presenting microparticles (MP-Ds) and HSPCs were observed in addressable microwell arrays, simulating cellular responses to localized niche signals. Long-term single-cell tracking revealed that MP-D interactions polarized HSPC lysosomes toward the contact site, directing division orientation and consequent asymmetric lysosomal inheritance in paired daughter cells. Furthermore, this co-culture system enhanced long-term hematopoietic reconstitution capacity of HSPCs in serial transplantations. Our findings support an association between HSPC ACD and the presentation mode of DLL1 signals, which enhances the ex vivo maintenance of HSPCs.","PeriodicalId":21885,"journal":{"name":"Stem Cell Reports","volume":" ","pages":"103059"},"PeriodicalIF":5.6,"publicationDate":"2026-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13555565/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148841137","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

Short-term gonadal cultures are sufficient for germline transmission in a songbird. 短期性腺培养足以在鸣禽中进行种系传播。

IF 5.6 2区医学

Stem Cell Reports Pub Date : 2026-09-08 Epub Date: 2026-08-20 DOI: 10.1016/j.stemcr.2026.103052

Matthew Biegler, Elijah Harter, Asha V Sidhu, Christina Szialta, Gillian Durham, Lotem Tchernichovski, Paul Collier, Ji-Dung Luo, Wei Wang, Ryan MacIsaac, Kirubel Belay, Thomas Carroll, Anna L Keyte, Erich D Jarvis

{"title":"Short-term gonadal cultures are sufficient for germline transmission in a songbird.","authors":"Matthew Biegler, Elijah Harter, Asha V Sidhu, Christina Szialta, Gillian Durham, Lotem Tchernichovski, Paul Collier, Ji-Dung Luo, Wei Wang, Ryan MacIsaac, Kirubel Belay, Thomas Carroll, Anna L Keyte, Erich D Jarvis","doi":"10.1016/j.stemcr.2026.103052","DOIUrl":"10.1016/j.stemcr.2026.103052","url":null,"abstract":"Primordial germ cells (PGCs) are reproductive stem cells that are valuable for avian biobanking and germline transmission. However, their long-term culture remains a challenge beyond a few poultry species. Here, we compare the transcriptomic impact and reproductive viability between short- and long-term chicken and zebra finch gonadal PGC culture protocols. Using single-cell transcriptomics, we identified rapid germline differentiation in zebra finch gonadal cultures compared to stable PGC identity in chicken, highlighting divergent signaling pathway responses to in vitro germline culture between species. These differentiation profiles were similarly found in low-serum zebra finch blood PGC cultures. Nonetheless, injections of these short-term zebra finch gonadal PGC cultures demonstrated sufficient gonadal reconstitution of host embryos to produce zebra finch germline chimeras and donor-derived offspring. This study demonstrates the minimal viability of short-term songbird gonadal cultures, and offers a roadmap to improve the longevity and self-renewal of non-poultry avian PGC cultures.","PeriodicalId":21885,"journal":{"name":"Stem Cell Reports","volume":" ","pages":"103052"},"PeriodicalIF":5.6,"publicationDate":"2026-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13555450/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148797986","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