STEM CELLS最新文献_第6页

Age-dependent role of histone deacetylase Sirt7 on haematopoiesis. 组蛋白去乙酰化酶Sirt7在造血中的年龄依赖性作用。

IF 4.8 2区医学

STEM CELLS Pub Date : 2026-04-25 DOI: 10.1093/stmcls/sxag005

Hannah Willems, Reinhard Bauer, Jörg P Müller

引用次数: 0

"Quiescence" in the resting zone of the growth plate: a systematic review. 生长板静息带的“静止”：系统综述。

IF 4.8 2区医学

STEM CELLS Pub Date : 2026-04-25 DOI: 10.1093/stmcls/sxag010

Mahtab Avijgan, Amal Nazaraliyev, Klas Blomgren, David Gomez-Cabrero, Phillip T Newton

{"title":"\"Quiescence\" in the resting zone of the growth plate: a systematic review.","authors":"Mahtab Avijgan, Amal Nazaraliyev, Klas Blomgren, David Gomez-Cabrero, Phillip T Newton","doi":"10.1093/stmcls/sxag010","DOIUrl":"10.1093/stmcls/sxag010","url":null,"abstract":"Postnatal skeletal growth in childhood and adolescence depends on cartilage organs called (epiphyseal) growth plates. Studies in the last decade have identified populations of skeletal stem cells within mouse growth plates' resting zones. While cellular quiescence is vital for the maintenance of many tissue-resident stem cell populations, the resting zone chondrocytes have been labeled \"quiescent\" for decades. However, the features of cellular quiescence that have been reported in the postnatal resting zone, how they were defined or experimentally assessed, and knowledge gaps relative to other quiescent cell types, remain to be well described. To address this, we conducted a systematic review, using the PRISMA guidelines, to identify studies of resting zone chondrocytes including the prefix \"quiescen*.\" Definitions, keywords, chronological data and experimental findings were extracted. Our analysis demonstrated that, compared to those in other well-studied tissues, features of cellular quiescence in RZ chondrocytes remain poorly reported and underexplored, with limited molecular and functional characterization. Furthermore, while most identified studies reported changes in cell division parameters, integration between cues controlling resting zone cell quiescence is incomplete and heterogeneity among the various sub-populations of RZ cells/potential quiescent states is yet to be fully determined. This review identifies consensuses and knowledge gaps between studies and between quiescent RZ cells and those in other tissues and can act to enhance consistency and comparability in future studies of \"quiescence\" in the RZ chondrocytes.","PeriodicalId":231,"journal":{"name":"STEM CELLS","volume":" ","pages":""},"PeriodicalIF":4.8,"publicationDate":"2026-04-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13110114/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147375562","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

FAK inhibition following acute olfactory epithelial inflammation promotes neurogenesis and functional recovery through stem cell CNTF. 急性嗅觉上皮炎症后FAK抑制通过干细胞CNTF促进神经发生和功能恢复。

IF 4.8 2区医学

STEM CELLS Pub Date : 2026-03-26 DOI: 10.1093/stmcls/sxag011

Derek Cox, Brian Wang, Jaeden Pyburn, Morning Dove Rose, Diego J Rodriguez-Gil, Theo Hagg, Cuihong Jia

{"title":"FAK inhibition following acute olfactory epithelial inflammation promotes neurogenesis and functional recovery through stem cell CNTF.","authors":"Derek Cox, Brian Wang, Jaeden Pyburn, Morning Dove Rose, Diego J Rodriguez-Gil, Theo Hagg, Cuihong Jia","doi":"10.1093/stmcls/sxag011","DOIUrl":"10.1093/stmcls/sxag011","url":null,"abstract":"The sense of smell is maintained by regenerating olfactory sensory neurons (OSNs) from basal stem cells in the olfactory epithelium (OE). Acute inflammation destroys OSNs, causing hyposmia and anosmia, but activates basal cells. Manipulation of signaling pathways to promote basal cell proliferation and neuroregeneration would reveal novel therapeutic targets for smell deficits. We found that ciliary neurotrophic factor (CNTF) from horizontal basal cells (HBCs, quiescent stem cells) promotes neuroregeneration and functional recovery following methimazole-induced acute injury. Moreover, inhibition of focal adhesion kinase (FAK) upregulates CNTF in naïve OE. Here, we show that the small molecule FAK inhibitor increased CNTF expression in cultured primary HBCs isolated from methimazole-treated mice. Although methimazole-induced CNTF did not seem to be through FAK signaling, inducible cre-lox knockout of FAK in HBCs in mice further increased CNTF expression, as well as Mash1, a marker for globose basal cells (GBCs, neuronal progenitors), and GBC proliferation. Moreover, intranasal aspiration, but not systemic treatment, of a water-soluble pharmacological FAK inhibitor (FAK14) 3 days following methimazole, dose-dependently increased CNTF and Mash1 expression, and GBC proliferation. Intranasal FAK14 also enhanced methimazole-induced regeneration of new OSNs in CNTF+/+, but not in CNTF-/-, mice, demonstrating that FAK14 boosts neuroregeneration through additional CNTF following acute inflammation. Finally, intranasal FAK14 instillation following methimazole improved the functional recovery of smell. This study identifies the therapeutic potential of intranasal application of FAK inhibitors to enhance olfactory neuroregeneration and function following injury.","PeriodicalId":231,"journal":{"name":"STEM CELLS","volume":" ","pages":""},"PeriodicalIF":4.8,"publicationDate":"2026-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13064918/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147375526","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

iPSC-derived modeling of HLA-lacking hematopoiesis reveals clonal diversity in eltrombopag response in acquired aplastic anemia. ipsc衍生的缺乏hla的造血模型揭示了获得性再生障碍性贫血中电凝反应的克隆多样性。

IF 4.8 2区医学

STEM CELLS Pub Date : 2026-03-26 DOI: 10.1093/stmcls/sxag004

Honoka Takahashi, Luna Seoka, Rio Takahashi, Yoshinori Yoshida, Kazuhisa Chonabayashi, Katsuto Takenaka, Koichi Akashi, Hiroyuki Takamatsu, Tatsuya Imi, Yoshitaka Zaimoku, Kohei Hosokawa, Takamasa Katagiri

{"title":"iPSC-derived modeling of HLA-lacking hematopoiesis reveals clonal diversity in eltrombopag response in acquired aplastic anemia.","authors":"Honoka Takahashi, Luna Seoka, Rio Takahashi, Yoshinori Yoshida, Kazuhisa Chonabayashi, Katsuto Takenaka, Koichi Akashi, Hiroyuki Takamatsu, Tatsuya Imi, Yoshitaka Zaimoku, Kohei Hosokawa, Takamasa Katagiri","doi":"10.1093/stmcls/sxag004","DOIUrl":"10.1093/stmcls/sxag004","url":null,"abstract":"Acquired aplastic anemia (AA) is an immune-mediated bone marrow failure in which cytotoxic T lymphocytes (CTLs) target hematopoietic stem cells (HSCs). Approximately 30% of AA patients develop immune escape clones lacking specific HLA class I alleles (HLA[-]) through loss of heterozygosity in chromosome 6p (6pLOH) or somatic loss-of-function mutations. Eltrombopag (EPAG), a thrombopoietin receptor agonist (TPO-RA), demonstrates clinical efficacy in AA in combination with immunosuppressive therapy; however, its impact on HLA(-) HSCs and hematopoietic progenitor cells (HPCs) remains poorly understood. In this study, we evaluated the hematopoietic effects of EPAG using umbilical cord blood-derived HPCs and a humanized hematopoiesis model in immunodeficient (BRGS) mice. Furthermore, we established induced pluripotent stem cell (iPSC)-derived hematopoietic models encompassing five wild-type (WT) clones and seven HLA-lacking clones, differentiated them into HPCs, and assessed their responses to EPAG. EPAG selectively conferred a proliferative advantage to specific hematopoietic fractions in HLA(-) HPCs, distinct from that observed in WT HPCs. Molecular analyses revealed clone-dependent differences in CD110 expression and downstream effectors, including phosphorylated STAT5, FOXM1, and E2F1, indicating differential activation of TPO receptor-mediated signaling pathways among clones. These findings highlight the functional diversity of HLA(-) hematopoiesis and suggest that the hematopoietic response to EPAG is governed by clone-intrinsic signaling programs. Furthermore, our results provide new insights into how eltrombopag modulates clonal competition and hematopoietic recovery in immune-escape hematopoiesis, with potential implications for optimizing therapeutic strategies and predicting clinical response in patients with acquired AA.","PeriodicalId":231,"journal":{"name":"STEM CELLS","volume":" ","pages":""},"PeriodicalIF":4.8,"publicationDate":"2026-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146045866","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

Circadian timing optimizes allo-HSCT to prevent aGVHD: a breakthrough in chrono-immunotherapy. 昼夜节律优化同种异体造血干细胞移植预防aGVHD：时间免疫治疗的一个突破。

IF 4.8 2区医学

STEM CELLS Pub Date : 2026-03-26 DOI: 10.1093/stmcls/sxaf084

Xiaguang Huang, Hening Xu, Yanru Xia, Zeshan Lu, Shiwei Duan, Yongming Xia

引用次数: 0

Disease modeling of myocilin mutation-dependent normal tension glaucoma: human retinal ganglion cell susceptibility to unfolded protein response and mTOR signaling. 心肌蛋白突变依赖的正常张力性青光眼的疾病模型：人类视网膜神经节细胞对UPR和mTOR信号的易感性。

IF 4.8 2区医学

STEM CELLS Pub Date : 2026-02-23 DOI: 10.1093/stmcls/sxag009

Subrata Kumar Shil, Murali Subramani, Matthew J Van Hook, Fang Qiu, Iqbal Ahmad

{"title":"Disease modeling of myocilin mutation-dependent normal tension glaucoma: human retinal ganglion cell susceptibility to unfolded protein response and mTOR signaling.","authors":"Subrata Kumar Shil, Murali Subramani, Matthew J Van Hook, Fang Qiu, Iqbal Ahmad","doi":"10.1093/stmcls/sxag009","DOIUrl":"10.1093/stmcls/sxag009","url":null,"abstract":"Glaucoma represents a group of diseases where the unifying theme is the progressive degeneration of retinal ganglion cells (RGCs), causing irreversible vision loss. Mutations in the myocilin (MYOC) gene represent one of the most common genetic factors associated with primary open-angle glaucoma (POAG). However, the mechanism underlying MYOC mutation-associated POAG is poorly understood. Here, using human disease modeling of MYOC mutation (A445V)-dependent POAG, which is usually without ocular hypertension, we have tested a hypothesis that human RGCs (hRGCs) are the target of the mutant protein, making them vulnerable to degenerative changes. Examination of hRGCs generated from MYOCA445V POAG patient-specific induced pluripotent stem cells (iPSCs) revealed that their differentiation is adversely affected, compared to those generated from isogenic control iPSCs. Retinal ganglion cells regulatory and axon growth and guidance gene expression is decreased in patient-specific hRGCs vs isogenic controls. Consequently, the former display immature neurites and their ability to form synapses with the target cells and regenerate are compromised. Furthermore, they display immature networking physiology compared to isogenic controls. The pathological burden of the mutant protein is reflected in their preferential retention in the endoplasmic reticulum (ER) of patient-specific hRGCs, activating the unfolded protein response (UPR) toward mutation-associated developmental phenotype. Furthermore, we demonstrate that REDD1, a stress-induced factor, is a mechanistic link between the MYOCA445V-activated UPR axis and inhibited mTOR signaling, a critical regulator of RGC development and function. Ours is the first demonstration of MYOC mutation-dependent hRGC phenotype and posits a mechanism for hRGC susceptibility toward degeneration independent of ocular hypertension.","PeriodicalId":231,"journal":{"name":"STEM CELLS","volume":" ","pages":""},"PeriodicalIF":4.8,"publicationDate":"2026-02-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13017134/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146224698","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

Stem cell and bioengineering approaches for end-stage renal disease: a comprehensive review. 干细胞和生物工程方法治疗终末期肾脏疾病：综述。

IF 4.8 2区医学

STEM CELLS Pub Date : 2026-02-23 DOI: 10.1093/stmcls/sxag003

Yusuke Nishimura

{"title":"Stem cell and bioengineering approaches for end-stage renal disease: a comprehensive review.","authors":"Yusuke Nishimura","doi":"10.1093/stmcls/sxag003","DOIUrl":"10.1093/stmcls/sxag003","url":null,"abstract":"End-stage renal disease (ESRD) is a major global health burden, and current treatments, such as dialysis and kidney transplantation, remain constrained by donor shortages, procedure-related complications, and reduced long-term quality of life. Regenerative medicine, particularly stem cell-based approaches, offers promising next-generation strategies for kidney repair and replacement. This review summarizes the current understanding of kidney development and intrinsic regenerative capacity and evaluates the therapeutic potential of hematopoietic stem cells, mesenchymal stem cells (MSCs), kidney-derived stem cells, and induced pluripotent stem cell (iPSC)-derived kidney organoids. Evidence from preclinical models demonstrates renoprotective and immunomodulatory effects across multiple stem cell types, whereas early-phase clinical trials have reported favorable safety profiles and preliminary signals of the efficacy of MSC-based therapies. iPSC- and organoid-based approaches present additional challenges, including incomplete vascularization, immature nephron structures, risks of tumorigenicity, immune compatibility issues, and the need for reproducible good manufacturing practice (GMP)-compliant manufacturing. Advances in biomaterials, organoid engineering, and vascularization strategies may help overcome these barriers. Overall, stem cell-based regenerative therapies show substantial potential to complement or ultimately reduce the reliance on dialysis and transplantation. Continued technological innovations and rigorously designed clinical trials are critical to translate these promising approaches into clinical practice.","PeriodicalId":231,"journal":{"name":"STEM CELLS","volume":" ","pages":""},"PeriodicalIF":4.8,"publicationDate":"2026-02-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146008034","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

Profiling the secretome: maternal obesity impacts redox and adipogenic signaling during neonatal mesenchymal stem cell adipogenesis. 分析分泌组：产妇肥胖影响新生儿间充质干细胞脂肪形成过程中的氧化还原和脂肪生成信号。

IF 4.8 2区医学

STEM CELLS Pub Date : 2026-02-23 DOI: 10.1093/stmcls/sxag001

Sofía Bellalta, Erika Pinheiro-Machado, Paola Casanello, Marijke Faas, Torsten Plösch

{"title":"Profiling the secretome: maternal obesity impacts redox and adipogenic signaling during neonatal mesenchymal stem cell adipogenesis.","authors":"Sofía Bellalta, Erika Pinheiro-Machado, Paola Casanello, Marijke Faas, Torsten Plösch","doi":"10.1093/stmcls/sxag001","DOIUrl":"10.1093/stmcls/sxag001","url":null,"abstract":"Recent studies evidence an altered bioenergetic profile and higher adipogenic commitment in the mesenchymal stem cells (MSC) from neonates of mothers with obesity. We hypothesize that these alterations may also affect the secretome of these cells. The aim of this study was to characterize the secretome of MSCs from the offspring of women with obesity compared to the ones from normal-weight women, both before and during adipogenesis. Wharton's jelly-derived MSCs were isolated from newborns of normal-weight women (NW-MSC; Body Mass Index 18.5-24.5 kg/m2) and women with obesity (OB-MSC; Body Mass Index > 30 kg/m2) and cultured for 0, 5, and 21 days of adipogenesis. The secretome from these cells was collected during the three timepoints and characterized by mass spectrometry. Our findings reveal fundamental differences in the secretome profiles, primarily associated with pathways involved in cellular and metabolic processes. Maternal obesity was found to decrease redox capacity at day 0 but subsequently triggered a compensatory increase in redox proteins during adipogenesis of OB-MSCs. Additionally, OB-MSCs secreted higher levels of lipid synthesis-related proteins and proinflammatory adipokines, which may contribute to the dysregulated adipogenesis observed in obesity. These preliminary data indicate that maternal obesity programs the secretome of neonatal MSCs, supporting the hypothesis that maternal obesity imprints early progenitor cells and potentially dictates the future metabolic status of the offspring's adipocytes.","PeriodicalId":231,"journal":{"name":"STEM CELLS","volume":" ","pages":""},"PeriodicalIF":4.8,"publicationDate":"2026-02-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13026406/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145948196","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

Nicotinamide salvage is required for proliferation and sustaining self-renewal in undifferentiated embryonic stem cells. 在未分化的胚胎干细胞中，烟酰胺的修复是增殖和自我更新所必需的。

IF 4.8 2区医学

STEM CELLS Pub Date : 2026-02-23 DOI: 10.1093/stmcls/sxaf081

Mu-Jie Lu, Hsin-Ru Chan, Samiksha Deme, Paul A Oliphint, Jonghwan Kim, Patrick Allard, Xiaolu A Cambronne

{"title":"Nicotinamide salvage is required for proliferation and sustaining self-renewal in undifferentiated embryonic stem cells.","authors":"Mu-Jie Lu, Hsin-Ru Chan, Samiksha Deme, Paul A Oliphint, Jonghwan Kim, Patrick Allard, Xiaolu A Cambronne","doi":"10.1093/stmcls/sxaf081","DOIUrl":"10.1093/stmcls/sxaf081","url":null,"abstract":"Stem cells use oxidized nicotinamide adenine dinucleotide (NAD+) in distinct subcellular compartments to support self-renewal and to regulate chromatin. There is limited information, however, about the biosynthetic pathways that replenish intracellular NAD+, which is continuously turned over in undifferentiated mouse embryonic stem cells. Establishing specific metabolic inputs for maintaining self-renewal can help direct reprogramming efforts. We used single fluorescent protein biosensors for in situ NAD+ measurements in J1 mouse embryonic stem cells. Sensors and controls were localized to the nucleus, cytoplasm, and mitochondrial compartments. Using a specific inhibitor for nicotinamide salvage, we found that loss of this pathway depleted NAD+ concentrations in all three subcellular compartments in undifferentiated culture conditions. We determined that loss of nicotinamide salvage reduced colony size, extended cell cycle, and resulted in diminished expression of self-renewal markers. Supplementation with precursors in the nicotinamide salvage pathway bypassed the pharmacological block, replenished cytosolic NAD+ levels, and reversed the effects on colony size. Notably, supplementation with deaminated precursors did not replenish intracellular NAD+ levels, suggesting minimal contribution from this pathway at this stage. In support, expression data from multiple mouse and human lines showed that nicotinamide salvage pathway enzyme NAMPT was predominantly expressed at the embryonic stem cell stage compared to the enzymes in other NAD+ biosynthesis pathways. Collectively, the data showed that undifferentiated embryonic stem cells heavily rely on nicotinamide salvage, indicating that this dependency is conserved.","PeriodicalId":231,"journal":{"name":"STEM CELLS","volume":" ","pages":""},"PeriodicalIF":4.8,"publicationDate":"2026-02-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13189135/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145825450","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

miR-124 orchestrates epicardial-mesenchymal transformation and paracrine cardiomyocyte maturation in epicardial-specific Tcf21-PKR1 knockout mice. 在心外膜特异性tcf21-PKR1敲除小鼠中，miR-124协调心外膜-间充质转化和旁分泌心肌细胞成熟。

IF 3.6 2区医学

STEM CELLS Pub Date : 2026-02-23 DOI: 10.1093/stmcls/sxaf082

Himanshu Arora, Martina Vincenzi, Anais Audebrand, Amin Kremic, Carmine Gentile, Laurent Desaubry, Canan G Nebigil

{"title":"miR-124 orchestrates epicardial-mesenchymal transformation and paracrine cardiomyocyte maturation in epicardial-specific Tcf21-PKR1 knockout mice.","authors":"Himanshu Arora, Martina Vincenzi, Anais Audebrand, Amin Kremic, Carmine Gentile, Laurent Desaubry, Canan G Nebigil","doi":"10.1093/stmcls/sxaf082","DOIUrl":"10.1093/stmcls/sxaf082","url":null,"abstract":"During the heart development, epicardial-to-mesenchymal transition (EMT) drives the production of progenitor cell populations that contribute to heart formation; however, the molecular control of EMT and its paracrine effects on cardiomyocytes remain poorly elucidated. Here, we defined a novel PKR1-miR-124-SNAI2 signaling axis that orchestrates EMT and coordinates myocardial maturation. Conditional deletion of the prokineticin receptor (PKR1) in mice Tcf21+ epicardial cells caused embryonic lethality and congenital heart disease-like anomalies, including ventricular rupture, arrhythmia, myocardial fibrosis, and impaired contractility. Transcriptomic profiling revealed marked upregulation of miR-124, concurrent with deregulation of EMT genes and signatures of immature cardiomyocytes. Mechanistically, miR-124 directly targets the 3' untranslated region of SNAI2, suppressing this key EMT regulator, resulting in failed EMT, apoptosis, and fibrosis in the epicardium. Functional rescue through miR-124 inhibition or PKR1 reintroduction restores SNAI2 expression, revives EMT, enhances cell survival, and promotes proper cardiomyocyte maturation. Paracrine effects were substantiated by conditioned media and ex vivo assays, demonstrating that epicardial-derived miR-124 suppressed cardiomyocyte contractility and cardiac maturity gene expression-thereby functionally linking epicardial disruption to myocardial immaturity. These findings establish miR-124 as a critical mediator of epicardial-myocardial communication with PKR1 as its upstream regulator. By integrating epicardial plasticity, myocardial maturation, and ECM homeostasis, our work reveals that targeting the PKR1-miR-124-SNAI2 pathway offers a novel mechanistic framework and potential therapeutic target for preventing or treating congenital heart disease.","PeriodicalId":231,"journal":{"name":"STEM CELLS","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2026-02-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145848529","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