Stem Cell Reports最新文献_第9页

Human CRX regulates photoreceptor cells development via bidirectional transcriptional control in retinal organoids. 人类CRX通过视网膜类器官的双向转录控制来调节光感受器细胞的发育。

IF 5.1 2区医学

Stem Cell Reports Pub Date : 2026-01-13 Epub Date: 2025-12-18 DOI: 10.1016/j.stemcr.2025.102747

Yuan Wang, Bingbing Xie, Xiaojing Song, Guanjie Gao, Yuanyuan Guan, Dandan Zheng, Ping Xu, Xiufeng Zhong

{"title":"Human CRX regulates photoreceptor cells development via bidirectional transcriptional control in retinal organoids.","authors":"Yuan Wang, Bingbing Xie, Xiaojing Song, Guanjie Gao, Yuanyuan Guan, Dandan Zheng, Ping Xu, Xiufeng Zhong","doi":"10.1016/j.stemcr.2025.102747","DOIUrl":"10.1016/j.stemcr.2025.102747","url":null,"abstract":"CRX (cone-rod homeobox) is a key regulator of retinal photoreceptor development, yet its human-specific functions remain poorly understood due to scarce human retinal tissues and significant species differences. Here, we established a human CRX-mCherry fluorescent reporter retinal organoid (RO) model to dissect CRX-mediated gene regulation. Using FACS, RNA sequencing, and Cleavage Under Targets and Tagmentation (CUT&Tag) sequencing, we identified CRX target genes and revealed its dual regulatory role: it activates photoreceptor-specific genes (e.g., RP1L1, linked to inherited retinal degeneration) in a dose-dependent manner, while suppressing non-photoreceptor genes (e.g., PCDH8 and PROX1). Notably, we first generated the human CRX CUT&Tag dataset, providing direct insights into CRX's genome-wide regulatory landscape in photoreceptor cell development. These findings demonstrate that CRX functions as both a transcriptional activator and repressor, ensuring photoreceptor-specific gene expression and preventing aberrant cell fate transitions. Our study provides critical insights into the role of human CRX in retinal development and implications for retinal degenerative diseases.","PeriodicalId":21885,"journal":{"name":"Stem Cell Reports","volume":" ","pages":"102747"},"PeriodicalIF":5.1,"publicationDate":"2026-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12925966/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145794811","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

Atypical cell cycle regulation over neural stem cell expansion. 非典型细胞周期对神经干细胞扩增的调控。

IF 5.1 2区医学

Stem Cell Reports Pub Date : 2026-01-13 Epub Date: 2026-01-02 DOI: 10.1016/j.stemcr.2025.102752

Dorota Lubanska, Ingrid Qemo, Keith Franklin Stringer, Hema Priya Mahendran, Bre-Anne Fifield, Alan Cieslukowski, Sami Alrashed, Youshaa El-Abed, Emmanuel Boujeke, Alexander Rodzinka, Elizabeth Fidalgo da Silva, Stephanie Dinescu, Alexandra Sorge, Srinath Kandalam, Dalton Liwanpo, Jillian Brown, Hasan Ghafoor, Maheen Arshad, Lisa A Porter

{"title":"Atypical cell cycle regulation over neural stem cell expansion.","authors":"Dorota Lubanska, Ingrid Qemo, Keith Franklin Stringer, Hema Priya Mahendran, Bre-Anne Fifield, Alan Cieslukowski, Sami Alrashed, Youshaa El-Abed, Emmanuel Boujeke, Alexander Rodzinka, Elizabeth Fidalgo da Silva, Stephanie Dinescu, Alexandra Sorge, Srinath Kandalam, Dalton Liwanpo, Jillian Brown, Hasan Ghafoor, Maheen Arshad, Lisa A Porter","doi":"10.1016/j.stemcr.2025.102752","DOIUrl":"10.1016/j.stemcr.2025.102752","url":null,"abstract":"Populations of adult neural stem cells (NSCs) that reside in the mammalian brain aid in neurogenesis throughout life and can be identified by a type VI intermediate filament protein, Nestin. Cell cycle regulation plays an important role in maintaining a balance between self-renewal and differentiation and determining the fate of NSCs. Data from our group and others support that the atypical cyclin-like protein SPY1 (also called RingoA; gene SPDYA) plays a critical role in activating NSCs from a quiescent state. Elevated levels of Spy1 are found in aggressive human brain cancers, including glioblastoma. Using a conditional mouse model, we demonstrate that driving the expression of Spy1, in the Nestin-enriched NSC population of the brain, increases stemness characteristics, decreases differentiation, and increases susceptibility to oncogenic transformation. This study contributes to better understanding of intricate cell cycle mechanisms that lead to deviation from the homeostatic state, promoting aberrant changes in adult NSCs.","PeriodicalId":21885,"journal":{"name":"Stem Cell Reports","volume":" ","pages":"102752"},"PeriodicalIF":5.1,"publicationDate":"2026-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12925950/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145896831","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

Hsp70-Bim interaction mediated mitophagy as a potential therapeutic target for CML stem cells. Hsp70-Bim相互作用介导的线粒体自噬作为CML干细胞的潜在治疗靶点。

IF 5.1 2区医学

Stem Cell Reports Pub Date : 2026-01-13 Epub Date: 2025-12-26 DOI: 10.1016/j.stemcr.2025.102751

Ting Song, Yang Song, Hong Zhang, Zhiyuan Hu, Fangkui Yin, Maojun Jiang, Yanxin Zhang, Ziqian Wang, Zhichao Zhang

{"title":"Hsp70-Bim interaction mediated mitophagy as a potential therapeutic target for CML stem cells.","authors":"Ting Song, Yang Song, Hong Zhang, Zhiyuan Hu, Fangkui Yin, Maojun Jiang, Yanxin Zhang, Ziqian Wang, Zhichao Zhang","doi":"10.1016/j.stemcr.2025.102751","DOIUrl":"10.1016/j.stemcr.2025.102751","url":null,"abstract":"In chronic myeloid leukemia (CML), disease persistence in patients is maintained by leukemic stem cells (LSCs), which drive tyrosine kinase inhibitor (TKI) resistance. Autophagy has been proposed as a potential therapy to eradicate CML LSCs. Here, using a small-molecule inhibitor of Hsp70 (heat shock protein 70)-Bim (Bcl-2-interacting mediator of cell death) interaction, S1-10, we demonstrate that Hsp70-Bim is a target for CML stemness maintenance. Hsp70-Bim is driven by Bcr-Abl and mediates particularly stronger mitophagy in CML LSCs than differentiated CML cells and HSCs. The more selective mitophagy regulation of Hsp70-Bim than ULK1 (unc-51-like autophagy activating kinase 1) is illustrated. Pharmacological inhibition of Hsp70-Bim blocks mitophagy, leading to the differentiation of CML LSCs, loss of quiescence, and loss of LSC self-renewal potential. In the patient-derived xenograft (PDX) CML models, S1g-10 reduces the number of LSCs by more than 80% after two weeks of injection, without obvious toxicity on normal red blood cells.","PeriodicalId":21885,"journal":{"name":"Stem Cell Reports","volume":" ","pages":"102751"},"PeriodicalIF":5.1,"publicationDate":"2026-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12925951/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145847016","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

Pluripotent stem cell lines available for use in clinical applications: A comprehensive overview. 可用于临床应用的多能干细胞系：全面概述。

IF 5.1 2区医学

Stem Cell Reports Pub Date : 2026-01-13 Epub Date: 2025-12-18 DOI: 10.1016/j.stemcr.2025.102741

Melissa K Carpenter, Tenneille E Ludwig

引用次数: 0

Chaperonin proteins CCT5 and CCT7 epigenetically restrict the transition from pluripotency to totipotency in embryonic stem cells. 伴侣蛋白CCT5和CCT7在表观遗传学上限制胚胎干细胞从多能性到全能性的转变。

IF 5.1 2区医学

Stem Cell Reports Pub Date : 2026-01-13 Epub Date: 2025-12-26 DOI: 10.1016/j.stemcr.2025.102750

Jiali Jiang, Zhiyong Liu, Xiaye Miao, Shilong Han, Min Li, Linxi Xie, Hejiao Zhang, Fuwen Zuo, Qingsheng Han

{"title":"Chaperonin proteins CCT5 and CCT7 epigenetically restrict the transition from pluripotency to totipotency in embryonic stem cells.","authors":"Jiali Jiang, Zhiyong Liu, Xiaye Miao, Shilong Han, Min Li, Linxi Xie, Hejiao Zhang, Fuwen Zuo, Qingsheng Han","doi":"10.1016/j.stemcr.2025.102750","DOIUrl":"10.1016/j.stemcr.2025.102750","url":null,"abstract":"As members of the CCT family, CCT5 and CCT7 play pivotal roles in telomerase trafficking, with their depletion resulting in TCAB1 protein loss and impaired telomere maintenance. However, their functional significance in embryonic stem cells (ESCs) state transitions remains incompletely understood. Here, we demonstrate that CCT5 or CCT7 deficiency disrupts telomere length homeostasis, triggering DNA damage response pathways and inducing epigenetic reprogramming. This cascade enhances cellular plasticity, activates repeat elements and 2-cell transcriptional programs, and facilitates the generation of 2-cell-like cells, suggesting that CCT5 and CCT7 may serve as epigenetic barriers restricting the transition from pluripotency to totipotency. Additionally, CCT5/7 stabilizes pluripotency through Wnt/β-catenin signaling: CCT7 directly binds β-catenin to facilitate nuclear translocation, while CCT5 dissociates E-cadherin/β-catenin complexes. These findings underscore the dual role of CCT5 and CCT7 in maintaining telomere integrity and regulating pluripotent state dynamics.","PeriodicalId":21885,"journal":{"name":"Stem Cell Reports","volume":" ","pages":"102750"},"PeriodicalIF":5.1,"publicationDate":"2026-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12925953/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145847025","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

Mitochondrial pyruvate metabolism in club cells drives airway inflammation. 俱乐部细胞中的线粒体丙酮酸代谢驱动气道炎症。

IF 5.1 2区医学

Stem Cell Reports Pub Date : 2026-01-13 Epub Date: 2025-12-18 DOI: 10.1016/j.stemcr.2025.102742

Jianhai Wang, Chunnan Du, De Hao, Qian Wu, Biyu Gui, Yu Li, Kuan Li, Xue Li, Qiuyang Zhang, Li Li, Huaiyong Chen

{"title":"Mitochondrial pyruvate metabolism in club cells drives airway inflammation.","authors":"Jianhai Wang, Chunnan Du, De Hao, Qian Wu, Biyu Gui, Yu Li, Kuan Li, Xue Li, Qiuyang Zhang, Li Li, Huaiyong Chen","doi":"10.1016/j.stemcr.2025.102742","DOIUrl":"10.1016/j.stemcr.2025.102742","url":null,"abstract":"Asthma is a chronic inflammatory airway disease characterized by defective epithelial repair, resulting from metabolic dysregulation in facultative progenitor cells. Here, we investigate how pyruvate metabolism in airway club cells controls epithelial differentiation and allergic airway inflammation. Single-cell transcriptomics revealed elevated glycolytic activity in club and goblet cells from patients with asthma. In an ovalbumin (OVA)-induced asthma model, conditional deletion of Mpc2-but not Ldha-in club cells impaired club-to-goblet cell differentiation, reduced CLCA3 and Foxa3 expression, and attenuated eosinophilic inflammation and Il-13 expression. Mpc2 loss increased Cxcl17 expression in club cells, promoting Cxcl17-Cxcr4 signaling with alveolar macrophages that suppressed CCL17-mediated type 2 inflammation. Neutralizing CCL17 phenocopied the Mpc2 knockout by reducing airway inflammation and goblet cell differentiation. These findings reveal a metabolic-immune crosstalk underlying asthma pathogenesis and identify mitochondrial pyruvate metabolism as a therapeutic target to limit epithelial remodeling and type 2 inflammation.","PeriodicalId":21885,"journal":{"name":"Stem Cell Reports","volume":" ","pages":"102742"},"PeriodicalIF":5.1,"publicationDate":"2026-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12925956/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145794916","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

Adjusting PSC culture for neural organoid generation. 调整PSC培养以产生神经类器官。

IF 5.1 2区医学

Stem Cell Reports Pub Date : 2026-01-13 Epub Date: 2025-12-04 DOI: 10.1016/j.stemcr.2025.102724

Magdalena A Sutcliffe, Pia Jensen, Joycelyn Tan, Charles A J Morris, Daniel J Fazakerley, Martin R Larsen, Madeline A Lancaster

{"title":"Adjusting PSC culture for neural organoid generation.","authors":"Magdalena A Sutcliffe, Pia Jensen, Joycelyn Tan, Charles A J Morris, Daniel J Fazakerley, Martin R Larsen, Madeline A Lancaster","doi":"10.1016/j.stemcr.2025.102724","DOIUrl":"10.1016/j.stemcr.2025.102724","url":null,"abstract":"Cerebral organoids generated according to unguided protocols produce neural tissue with exceptional cell diversity and fidelity to in vivo. However, with only minimal extrinsic intervention, the importance of high-quality starting material becomes paramount. Understanding quality and how to maintain it throughout prolonged culture is therefore a crucial foundation for successful organoid differentiation. In this study, we investigate the proteome and phosphoproteome of human pluripotent stem cells to uncover the mechanisms that drive neural organoid competence. We identify aberrant cell-extracellular matrix interaction and increased oxidative metabolism as hallmarks of poor neural differentiators. Drawing on the proteomic data and published literature, we test culture conditions with improved coating matrix, reduction of oxidative stress, and sustained fibroblast growth Factor 2 (FGF2) supply. These adjustments provide some improvement to differentiation, highlighting the importance of optimal culture conditions to maintain high-quality stem cells but also suggesting cell-intrinsic sources of variability.","PeriodicalId":21885,"journal":{"name":"Stem Cell Reports","volume":" ","pages":"102724"},"PeriodicalIF":5.1,"publicationDate":"2026-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12925955/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145687930","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 role of m6A RNA methylation in the maintenance of X chromosome inactivation and X-to-autosome dosage compensation in early embryonic lineages. 早期胚胎谱系中m6A RNA甲基化在维持X染色体失活和X-常染色体剂量补偿中的作用。

IF 5.1 2区医学

Stem Cell Reports Pub Date : 2026-01-13 Epub Date: 2025-12-11 DOI: 10.1016/j.stemcr.2025.102740

Hemant C Naik, Runumi Baro, Amritesh Sarkar, Muralidhar Nayak, Kartik Sunagar, Srimonta Gayen

{"title":"The role of m6A RNA methylation in the maintenance of X chromosome inactivation and X-to-autosome dosage compensation in early embryonic lineages.","authors":"Hemant C Naik, Runumi Baro, Amritesh Sarkar, Muralidhar Nayak, Kartik Sunagar, Srimonta Gayen","doi":"10.1016/j.stemcr.2025.102740","DOIUrl":"10.1016/j.stemcr.2025.102740","url":null,"abstract":"In mammals, while X chromosome inactivation (XCI) balances the dosage of X-linked gene expression between sexes, upregulation of active-X balances the dosage of monoallelic X-linked genes with biallelic autosomal genes (AA). Here, we have investigated the role of m6A RNA methylation in the maintenance of XCI and X-to-autosome (X-to-A) dosage compensation in early embryonic lineages: epiblast stem cells (EpiSCs), trophoblast stem cells (TSCs), and extraembryonic endoderm stem cells (XENs). We find that the depletion of m6A RNA methylation in these cells does not affect the maintenance of inactive-X silencing. Moreover, we show that m6A marks are less enriched on X-linked transcripts than the autosomal transcripts in early embryonic lineages. Notably, we demonstrate that the extent of X-to-A dosage compensation varies with m6A methylation level. Finally, we show that the depletion of m6A partly disrupts X-to-A dosage compensation in a cell-type-specific manner. Together, our study provides significant insight into the role of m6A RNA methylation in dosage compensation.","PeriodicalId":21885,"journal":{"name":"Stem Cell Reports","volume":" ","pages":"102740"},"PeriodicalIF":5.1,"publicationDate":"2026-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12925958/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145744623","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

Alternative splicing dynamics during human cardiac development in vivo and in vitro. 人类心脏在体内和体外发育过程中的选择性剪接动力学。

IF 5.1 2区医学

Stem Cell Reports Pub Date : 2026-01-13 Epub Date: 2026-01-02 DOI: 10.1016/j.stemcr.2025.102757

Beatriz Gomes-Silva, Marta Furtado, Marta Ribeiro, Sandra Martins, Teresa Carvalho, André Ventura-Gomes, Henrike Maatz, Pragati Parakkat, Claudia Crocini, Michael Gotthardt, Rosina Savisaar, Maria Carmo-Fonseca

{"title":"Alternative splicing dynamics during human cardiac development in vivo and in vitro.","authors":"Beatriz Gomes-Silva, Marta Furtado, Marta Ribeiro, Sandra Martins, Teresa Carvalho, André Ventura-Gomes, Henrike Maatz, Pragati Parakkat, Claudia Crocini, Michael Gotthardt, Rosina Savisaar, Maria Carmo-Fonseca","doi":"10.1016/j.stemcr.2025.102757","DOIUrl":"10.1016/j.stemcr.2025.102757","url":null,"abstract":"Cardiomyocytes differentiated in vitro from human induced pluripotent stem cells (iPSC-CMs) are increasingly used in studies of disease mechanisms, drug development, toxicity testing, and regenerative medicine. Alternative splicing (AS) plays a pivotal role in cardiac development. However, the extent to which iPSC-CMs recapitulate native cardiac splicing patterns remains poorly understood. Here, we provide a comprehensive temporal map of AS regulation during human cardiac development. iPSC-derived cardiomyocytes globally recapitulate the transcriptome of prenatal cardiomyocytes, yet their splicing profiles remain heterogeneous, with certain events reflecting early embryonic patterns and others resembling those of later-stage fetal hearts. Moreover, we uncover altered splicing events in iPSC-CMs, including mis-splicing of splicing factors. In conclusion, we present a resource of AS dynamics throughout human cardiac development and a catalog of splicing markers to assess cardiomyocyte maturation in vitro. Our findings provide critical insights into the limitations of iPSC-CM models and their utility in cardiovascular research.","PeriodicalId":21885,"journal":{"name":"Stem Cell Reports","volume":" ","pages":"102757"},"PeriodicalIF":5.1,"publicationDate":"2026-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12925949/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145896815","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

Autophagy is required for the development and functionality of lacrimal gland-like organoids. 自噬是泪腺样器官发育和功能的必要条件。

IF 5.1 2区医学

Stem Cell Reports Pub Date : 2026-01-13 Epub Date: 2025-12-18 DOI: 10.1016/j.stemcr.2025.102744

Gamze Kocak, Miriam E Korsgen, Leticia F Amores, Congxin Sun, Merve Ceylan, Asmaa Ghazwani, Merve Kandirici, Malgorzata Zatyka, Elena Seranova, Animesh Acharjee, Timothy Barrett, Bayram Yuksel, Adil Mardinoglu, Sinan Güven, Sovan Sarkar

{"title":"Autophagy is required for the development and functionality of lacrimal gland-like organoids.","authors":"Gamze Kocak, Miriam E Korsgen, Leticia F Amores, Congxin Sun, Merve Ceylan, Asmaa Ghazwani, Merve Kandirici, Malgorzata Zatyka, Elena Seranova, Animesh Acharjee, Timothy Barrett, Bayram Yuksel, Adil Mardinoglu, Sinan Güven, Sovan Sarkar","doi":"10.1016/j.stemcr.2025.102744","DOIUrl":"10.1016/j.stemcr.2025.102744","url":null,"abstract":"Lacrimal glands (LGs) serve as pivotal exocrine glands crucial for protecting the ocular surface. Dysfunction in LG cell composition or secretion is implicated in dry eye disease (DED). While autophagy plays a vital role in tissue homeostasis in many organs, how it affects LG development and secretory function is not known. Here, we have undertaken a genetic study by utilizing autophagy-deficient human embryonic stem cells (hESCs) and differentiating them into LG-like organoids. Autophagy-deficient LG-like organoids exhibited improper development and secretion, along with increased protein aggregation, proliferation, and cell death. These phenotypes were associated with an accumulation of PAX6, a transcription factor crucial for brain and eye development, which we identified as an autophagy substrate. Pharmacological interventions with nicotinamide mononucleotide (NMN) and melatonin were able to rescue the cellular dysfunction in autophagy-deficient LG-like organoids. Together, our study highlights the role of autophagy in LG along with potential therapeutic interventions for DED.","PeriodicalId":21885,"journal":{"name":"Stem Cell Reports","volume":" ","pages":"102744"},"PeriodicalIF":5.1,"publicationDate":"2026-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12925961/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145794891","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