Stem Cell Reports最新文献_第4页

From stem cells to somites: Revealing genetic and exogenous factors of human embryogenesis. 从干细胞到体细胞：揭示人类胚胎发生的遗传和外源因素。

IF 5.6 2区医学

Stem Cell Reports Pub Date : 2026-09-08 Epub Date: 2026-08-06 DOI: 10.1016/j.stemcr.2026.103023

Maria Teresa Alejo-Vinogradova, Yunna E Strøm, Lieke A Lamers, Yolanda W Chang, Martijn J Hendriksen, Mariya Moosajee, Michiel Vermeulen, Suzan Stelloo

{"title":"From stem cells to somites: Revealing genetic and exogenous factors of human embryogenesis.","authors":"Maria Teresa Alejo-Vinogradova, Yunna E Strøm, Lieke A Lamers, Yolanda W Chang, Martijn J Hendriksen, Mariya Moosajee, Michiel Vermeulen, Suzan Stelloo","doi":"10.1016/j.stemcr.2026.103023","DOIUrl":"10.1016/j.stemcr.2026.103023","url":null,"abstract":"Stem-cell-based human embryo models offer an ethically tractable platform for studying early human development. This study employs somitoids, three-dimensional models of human somitogenesis, to investigate how transcriptional programs and culture conditions influence somite formation and segmentation. We show that pre-differentiation culture medium impacts the developmental potential of induced pluripotent stem cells (iPSCs), with StemFit medium and Matrigel embedding outperforming mTeSR Plus medium in generating robust somite-like structures. Strikingly, these differences arise despite only subtle changes in transcriptomic and time-resolved proteomic profiles. P300-based proximity labeling also reveals a largely overlapping set of chromatin-associated regulators across iPSC conditions. In somitoids, enhancer-associated profiling highlights factors linked to somitogenesis, including MESP2 and TBX6. Knockout of three identified regulators, BPTF, RBPJ, and CITED2, demonstrate their essential roles in somite formation. Together, these findings highlight how culture conditions and enhancer-associated networks influence early human development and demonstrate somitoids as a scalable system for functional genomics.","PeriodicalId":21885,"journal":{"name":"Stem Cell Reports","volume":" ","pages":"103023"},"PeriodicalIF":5.6,"publicationDate":"2026-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13555414/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148685770","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

TGFβ-dependent upregulation of OCIAD2 is essential for epithelial-to-mesenchymal transition during mesendoderm differentiation. 在中胚层分化过程中，依赖tgf β的OCIAD2的上调对于上皮细胞向间质细胞的转变至关重要。

IF 5.6 2区医学

Stem Cell Reports Pub Date : 2026-09-08 Epub Date: 2026-08-06 DOI: 10.1016/j.stemcr.2026.103025

Kajal Kamat, Maneesha S Inamdar

{"title":"TGFβ-dependent upregulation of OCIAD2 is essential for epithelial-to-mesenchymal transition during mesendoderm differentiation.","authors":"Kajal Kamat, Maneesha S Inamdar","doi":"10.1016/j.stemcr.2026.103025","DOIUrl":"10.1016/j.stemcr.2026.103025","url":null,"abstract":"Deciphering the mechanisms that govern lineage commitment of human pluripotent stem cells (hPSCs) is essential for optimizing differentiation strategies. Here, we uncover the role of the mitochondrial protein OCIAD2 in hPSC fate decisions. We show that OCIAD2 is transiently upregulated during mesendoderm differentiation in response to TGFβ/Activin A signaling. OCIAD2 depletion disrupted TGFβ and WNT signaling, impaired mesendoderm specification, and resulted in an incomplete epithelial-to-mesenchymal transition (EMT). Furthermore, OCIAD2 loss reduced mitochondrial dynamics and fatty acid oxidation, indicating dysregulated lipid metabolism. Transcriptome and biochemical analysis of OCIAD2-knockout (KO) and -overexpressing (OV) hESCs identified OCIAD2 as a positive regulator of TGFβ signaling. Supplementation with acetate alongside Wnt3a increased SMAD2/3 acetylation and restored mesendoderm differentiation in KO. We propose that OCIAD2 integrates metabolic cues with TGFβ signaling to regulate EMT. This study provides new insight into how mitochondrial proteins influence lineage commitment, highlighting broader implications for developmental biology and tumor progression.","PeriodicalId":21885,"journal":{"name":"Stem Cell Reports","volume":" ","pages":"103025"},"PeriodicalIF":5.6,"publicationDate":"2026-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13555442/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148685783","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

Generation of effector CD4⁺ T cells from human iPSC. 从人iPSC中产生效应CD4+ T细胞。

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.2026.103058

Julian Amirault, Dar Heinze, Mengwei Yang, Charles M Kerr, Pushpinder S Bawa, Laura Polanco, Gabriel M Sgambettera, Feiya Wang, Anna C Belkina, Jennifer E Snyder-Cappione, Gustavo Mostoslavsky

{"title":"Generation of effector CD4+ T cells from human iPSC.","authors":"Julian Amirault, Dar Heinze, Mengwei Yang, Charles M Kerr, Pushpinder S Bawa, Laura Polanco, Gabriel M Sgambettera, Feiya Wang, Anna C Belkina, Jennifer E Snyder-Cappione, Gustavo Mostoslavsky","doi":"10.1016/j.stemcr.2026.103058","DOIUrl":"10.1016/j.stemcr.2026.103058","url":null,"abstract":"Off-the-shelf T cell therapies could be transformative in chimeric antigen receptor (CAR) therapies for cancers and treatment of chronic inflammatory diseases. However, challenges remain in generating CD4+ T cells from induced pluripotent stem cells (iPSCs). We describe a key role for the withdrawal of Notch ligand during T cell receptor stimulation of CD4/CD8 double-positive progenitors allowing access to the CD4+ lineage in iPSC T cells (iCD4+ T cells). Functional analyses of iCD4+ T cells by using a novel high-parameter cytometry by time-of-flight (CyTOF) intracellular cytokine panel revealed canonical Th1 cytokine signatures and cells producing varying combinations of other cytokines, including IL-4, IL-8, and IL-13. Single-cell RNA sequencing of iCD4+ T cells demonstrated a transcriptional signature similar to human peripheral CD4+ T cells. We believe this robust yet simple platform represents a key step toward off-the-shelf iCD4+ T cell therapies with utility for the treatment of a panoply of diseases including cancer and inflammatory autoimmune disorders.","PeriodicalId":21885,"journal":{"name":"Stem Cell Reports","volume":" ","pages":"103058"},"PeriodicalIF":5.6,"publicationDate":"2026-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13555550/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148841070","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

Development and validation of a long-term co-maturation protocol for human stem cell-derived microglia and neuronal networks. 人类干细胞衍生的小胶质细胞和神经网络长期共成熟方案的开发和验证。

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.2026.103053

Annika Mordelt, Imke M E Schuurmans, Nicky Scheefhals, Marina P Hommersom, Koen Slottje, Kimberly Mast, Mara Graziani, Carlos O González, Klaas W Mulder, Laura J A Wingens, Dirk Schubert, Nael Nadif Kasri, Lot D de Witte

{"title":"Development and validation of a long-term co-maturation protocol for human stem cell-derived microglia and neuronal networks.","authors":"Annika Mordelt, Imke M E Schuurmans, Nicky Scheefhals, Marina P Hommersom, Koen Slottje, Kimberly Mast, Mara Graziani, Carlos O González, Klaas W Mulder, Laura J A Wingens, Dirk Schubert, Nael Nadif Kasri, Lot D de Witte","doi":"10.1016/j.stemcr.2026.103053","DOIUrl":"10.1016/j.stemcr.2026.103053","url":null,"abstract":"Microglia-neuron interactions play a key role in a variety of central nervous system disorders. Technologies using human induced pluripotent stem cells (hiPSCs) have been developed to model human brain cells with the goal to understand their function. To effectively study neuro-immune crosstalk and investigate microglial contributions to neuronal network development and function, both microglia and neurons should co-mature allowing for long-term interactions throughout their differentiation. Here, we present a co-maturation protocol that robustly generates glutamatergic neuronal networks containing hiPSC-derived microglia. We validated the long-term co-cultures using single-cell transcriptomics, imaging, and neuronal activity readouts. In this protocol, astrocytes were required for long-term survival of microglia and for their integration into neuronal networks. Our co-maturation approach induced the typical ramified microglia morphology and characteristic microglia-neuron interactions. Homeostatic markers such as P2RY12 and TMEM119 and neuronal remodeling-associated genes were upregulated compared to microglia monocultures, highlighting the necessity of the environment to generate and maintain the context-dependent microglia signature in vitro. In this manuscript, we include the full optimization process of our co-maturation approach, a comprehensive description of the protocol, practical guidelines, and troubleshooting tips. Our co-maturation model provides a powerful tool to assess the role of human microglia in modulating neuronal function and development in health and disease.","PeriodicalId":21885,"journal":{"name":"Stem Cell Reports","volume":" ","pages":"103053"},"PeriodicalIF":5.6,"publicationDate":"2026-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13555563/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148797767","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

Brain organoids in Alzheimer disease and related tauopathies: Challenges and opportunities for translational readiness. 阿尔茨海默病和相关病变的脑类器官：转化准备的挑战和机遇。

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.2026.103051

Anuj Guruacharya, Thomas Hartung, Roberta Souza Dos Reis, Natália Chermont Dos Santos Moreira, Liliana Attisano, Silvia Bolognin, Khalid Iqbal, Binita Rajbanshi

引用次数: 0

Metabolic reprogramming via LDHB confers resistance to lactate-induced dysfunction and enhanced antitumor activity in hiPSC-Derived NK cells. 通过LDHB的代谢重编程赋予hipsc来源的NK细胞抵抗乳酸诱导的功能障碍和增强的抗肿瘤活性。

IF 5.6 2区医学

Stem Cell Reports Pub Date : 2026-09-08 Epub Date: 2026-08-13 DOI: 10.1016/j.stemcr.2026.103048

Zhishuai Zhang, Yuchan Mai, Jun Tang, Jiaying Ning, Yanjiao Qin, Jiaming Gu, Zhaozong Cao, Jian Liu, Tiancheng Zhou, Junwei Wang, Jeane L Pan, Jiaheng Chen, Yanling Zhu, Guangjin Pan

{"title":"Metabolic reprogramming via LDHB confers resistance to lactate-induced dysfunction and enhanced antitumor activity in hiPSC-Derived NK cells.","authors":"Zhishuai Zhang, Yuchan Mai, Jun Tang, Jiaying Ning, Yanjiao Qin, Jiaming Gu, Zhaozong Cao, Jian Liu, Tiancheng Zhou, Junwei Wang, Jeane L Pan, Jiaheng Chen, Yanling Zhu, Guangjin Pan","doi":"10.1016/j.stemcr.2026.103048","DOIUrl":"10.1016/j.stemcr.2026.103048","url":null,"abstract":"Natural Killer (NK) cells generally exhibit dysfunction in tumor microenvironment (TME), significantly limiting their efficacy in antitumor therapy. Tumor cells display enhanced glycolysis, leading to lactic acid (LA) secretion and accumulation in the TME. Using human-induced pluripotent stem cell (hiPSC)-derived NK cells (iNKs) as a model, we demonstrate that LA induces substantial iNK dysfunction, including reduced survival, impaired IFN-γ secretion, and diminished tumor-killing capacity due to severely compromised mitochondrial function. To overcome LA-induced dysfunction, we knocked in an expression cassette for lactate dehydrogenase B (LDHB) into hiPSCs (LDHB-hiPSCs), enabling conversion of cellular lactate to pyruvate. iNKs derived from LDHB-hiPSCs (LDHB-iNKs) largely resisted LA-induced dysfunction, exhibiting enhanced cytotoxicity and improved survival in high-LA tumor tissues. Importantly, LDHB-iNKs show superior suppression of solid tumor formation in vivo. Our study provides a novel strategy to enhance NK cell therapy against solid tumors by reshaping the metabolic pathways.","PeriodicalId":21885,"journal":{"name":"Stem Cell Reports","volume":" ","pages":"103048"},"PeriodicalIF":5.6,"publicationDate":"2026-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13555463/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148760398","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

Suidae iPSC-derived macrophages as models for investigating susceptibility and resilience to African swine fever virus. 水蛭科ipsc衍生巨噬细胞作为研究非洲猪瘟病毒易感性和恢复力的模型。

IF 5.6 2区医学

Stem Cell Reports Pub Date : 2026-09-08 Epub Date: 2026-08-06 DOI: 10.1016/j.stemcr.2026.103046

Tom M Watson, Lynnette C Goatley, Stephen Meek, Lel Eory, Sylvia Kohler, Nicholas Berkley, Sofia Sternberg, Melany Jackson, Amy Findlay, Isabella Hoskins, Simon Girling, Joseph Mee, Alan L Archibald, Finn Grey, Falko Steinbach, Helen Crooke, Christopher L Netherton, Tom Burdon

{"title":"Suidae iPSC-derived macrophages as models for investigating susceptibility and resilience to African swine fever virus.","authors":"Tom M Watson, Lynnette C Goatley, Stephen Meek, Lel Eory, Sylvia Kohler, Nicholas Berkley, Sofia Sternberg, Melany Jackson, Amy Findlay, Isabella Hoskins, Simon Girling, Joseph Mee, Alan L Archibald, Finn Grey, Falko Steinbach, Helen Crooke, Christopher L Netherton, Tom Burdon","doi":"10.1016/j.stemcr.2026.103046","DOIUrl":"10.1016/j.stemcr.2026.103046","url":null,"abstract":"African swine fever virus (ASFV) causes a lethal hemorrhagic fever in pigs, and spread of this disease threatens many pig species (Suidae) globally. By contrast, ASFV infections in the natural evolved hosts, warthog and bushpig, are subclinical. The macrophage (Mϕ) is the primary target of ASFV, and species-dependent responses in Mϕs are presumed to influence disease susceptibility. In an attempt to model these differences in vitro, we generated transgene-regulated induced pluripotent stem cells (iPSCs) from domestic pig, wild boar, red river hog, and warthog and confirmed that their corresponding iPSC-derived Mϕs (iPSCdMs) supported infection and replication of ASFV. In contrast to the other species, however, warthog iPSCdMs did not induce interferon α upon infection by either virulent or attenuated ASFV. iPSCdMs may therefore represent an experimental system to understand how ASFV infection of Mϕs contributes to disease and aid development of strategies to combat this economically and environmentally devastating pathogen.","PeriodicalId":21885,"journal":{"name":"Stem Cell Reports","volume":" ","pages":"103046"},"PeriodicalIF":5.6,"publicationDate":"2026-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13555459/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148685793","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

CRISPR activation reveals SOX5/6/9 as key transcriptional regulators directing iPSC-derived cells toward a notochordal lineage. CRISPR激活揭示SOX5/6/9是引导ipsc衍生细胞向脊索谱系发展的关键转录调控因子。

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.2026.103060

Xiaole Tong, Marieke Visscher, Frank M Riemers, Danielle Versluis, Niels Geijsen, Peng Shang, Marianna A Tryfonidou, Deepani W Poramba-Liyanage

{"title":"CRISPR activation reveals SOX5/6/9 as key transcriptional regulators directing iPSC-derived cells toward a notochordal lineage.","authors":"Xiaole Tong, Marieke Visscher, Frank M Riemers, Danielle Versluis, Niels Geijsen, Peng Shang, Marianna A Tryfonidou, Deepani W Poramba-Liyanage","doi":"10.1016/j.stemcr.2026.103060","DOIUrl":"10.1016/j.stemcr.2026.103060","url":null,"abstract":"Intervertebral disc (IVD) degeneration, a leading cause of chronic lower back pain, is associated with loss of vacuolated notochordal cells (NCs) and fibrotic remodeling of the nucleus pulposus. Emerging therapies increasingly focus on NCs, which are rare but therapeutically relevant cells for regenerating degenerated IVDs. In this study, we used CRISPR-based transactivation (CRISPRa) to direct the differentiation of human induced pluripotent stem cells (iPSCs) into the NC lineage. We tested CRISPRa-mediated activation of NOTO, TBXT, FOXA2, SOX5, SOX6, and SOX9, coupled with single-cell sequencing of Aggrecan-2A-mScarlet reporter iPSCs. This approach identified the SOX5/6/9 combination (SOX-trio) as critical for promoting NC lineage commitment. The SOX-trio yielded the largest cell population expressing a range of genes previously associated with NC identity, including SHH, FOXA1, FOXA2, FOXJ1, FN1, ALCAM, KRT8, and KRT18. Our study demonstrates the integration of CRISPRa with single-cell technologies as a powerful platform for investigating and enriching iPSC-derived NCs, supporting future regenerative strategies across various fields.","PeriodicalId":21885,"journal":{"name":"Stem Cell Reports","volume":" ","pages":"103060"},"PeriodicalIF":5.6,"publicationDate":"2026-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13555567/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148841104","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

TDP-43 sustains satellite cells to maintain and regenerate skeletal muscle. TDP-43维持卫星细胞维持和再生骨骼肌。

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.2026.103050

Theodore E Ewachiw, Tenaya K Vallery, Shloka Dhar, Hayden Clarkson, Tiffany Elston, Haileigh Gay, Bradley B Olwin

{"title":"TDP-43 sustains satellite cells to maintain and regenerate skeletal muscle.","authors":"Theodore E Ewachiw, Tenaya K Vallery, Shloka Dhar, Hayden Clarkson, Tiffany Elston, Haileigh Gay, Bradley B Olwin","doi":"10.1016/j.stemcr.2026.103050","DOIUrl":"10.1016/j.stemcr.2026.103050","url":null,"abstract":"Skeletal muscle satellite cells (SCs), residing between the myofiber plasma membrane and the surrounding basement membrane, continue to maintain and repair skeletal muscle throughout life. Typically, quiescent SCs can transition into a reversible alert state (GAlert) that primes them for rapid activation to maintain or repair muscle. From GAlert, SCs can either re-enter quiescence or commit to the cell cycle, expand, and differentiate to fuse with existing regenerating myofibers. Exit from quiescence requires extensive post-transcriptional remodeling, including changes in RNA processing and RNA-binding protein activity. We show that TDP-43, an RNA-binding protein, is essential for SC maintenance and muscle repair. Conditional deletion of TDP-43 in SCs caused a consistent and progressive loss of GAlert SCs, even in uninjured muscle, leading to depletion of the SC pool. TDP-43 haploinsufficiency was sufficient to impair SC maintenance, indicating that both alleles are required. Integrative analysis suggests that TDP-43 supports the expression of stress response-associated transcripts during the quiescent-to- GAlert transition and that failure to mount this response contributes to SC apoptosis. Thus, we identified TDP-43 as a critical regulator of survival of SCs as these cells activate, and we establish that TDP-43 is required for the maintenance and repair of skeletal muscle.","PeriodicalId":21885,"journal":{"name":"Stem Cell Reports","volume":" ","pages":"103050"},"PeriodicalIF":5.6,"publicationDate":"2026-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13555458/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148797952","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

C9orf72-associated and sporadic FTD patient iPSC-microglia show differences in phagocytosis and gene expression. c9orf72相关和散发性FTD患者ipsc -小胶质细胞在吞噬和基因表达方面存在差异。

IF 5.6 2区医学

Stem Cell Reports Pub Date : 2026-09-08 Epub Date: 2026-08-06 DOI: 10.1016/j.stemcr.2026.103026

Hannah Rostalski, Tomi Hietanen, Dorit Hoffmann, Sami Heikkinen, Nadine Huber, Ashutosh Dhingra, Salvador Rodriguez-Nieto, Teemu Kuulasmaa, Sohvi Ohtonen, Henna Jäntti, Viivi Pekkala, Stina Leskelä, Petra Mäkinen, Kasper Katisko, Päivi Hartikainen, Šárka Lehtonen, Eino Solje, Jari Koistinaho, Tarja Malm, Anne M Portaankorva, Teemu Natunen, Henna Martiskainen, Mari Takalo, Mikko Hiltunen, Annakaisa Haapasalo

{"title":"C9orf72-associated and sporadic FTD patient iPSC-microglia show differences in phagocytosis and gene expression.","authors":"Hannah Rostalski, Tomi Hietanen, Dorit Hoffmann, Sami Heikkinen, Nadine Huber, Ashutosh Dhingra, Salvador Rodriguez-Nieto, Teemu Kuulasmaa, Sohvi Ohtonen, Henna Jäntti, Viivi Pekkala, Stina Leskelä, Petra Mäkinen, Kasper Katisko, Päivi Hartikainen, Šárka Lehtonen, Eino Solje, Jari Koistinaho, Tarja Malm, Anne M Portaankorva, Teemu Natunen, Henna Martiskainen, Mari Takalo, Mikko Hiltunen, Annakaisa Haapasalo","doi":"10.1016/j.stemcr.2026.103026","DOIUrl":"10.1016/j.stemcr.2026.103026","url":null,"abstract":"C9orf72 hexanucleotide repeat expansion (C9-HRE) is a major genetic cause of amyotrophic lateral sclerosis and frontotemporal dementia (FTD). However, approximately half of the FTD patients are sporadic without a clear genetic background. To compare characteristics of microglia from different FTD subtypes, we generated induced pluripotent stem cell-derived microglia (iMG) from sporadic and C9-HRE-carrying behavioral variant FTD (bvFTD) patients and healthy controls. C9-HRE iMG displayed C9-HRE-associated RNA foci and dipeptide repeat proteins. All bvFTD iMG had fewer LAMP2-A-positive vesicles compared to control iMG. Additionally, C9-HRE iMG showed significantly increased LC3BII/I conversion after bafilomycin A1 treatment and altered phagocytic activity. The gene expression profile of C9-HRE iMG only modestly differed from the control iMG, but was greatly different from the sporadic bvFTD patient iMG. Our data show alterations in phagocytic and autophagosomal/lysosomal pathways and gene expression profiles between C9-HRE and sporadic bvFTD iMG for the first time.","PeriodicalId":21885,"journal":{"name":"Stem Cell Reports","volume":" ","pages":"103026"},"PeriodicalIF":5.6,"publicationDate":"2026-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13555443/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148685788","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