Stem Cell Reviews and Reports最新文献

{"title":"'Nomadic' Hematopoietic Stem Cells Navigate the Embryonic Landscape.","authors":"Anand Badhri Narayan, Senthil Kumar Hariom, Ayan Prasad Mukherjee, Deotima Das, Aadhira Nair, Everette Jacob Remington Nelson","doi":"10.1007/s12015-025-10843-6","DOIUrl":"10.1007/s12015-025-10843-6","url":null,"abstract":"<p><p>Hematopoietic stem cells are a unique population of tissue-resident multipotent cells with an extensive ability to self-renew and regenerate the entire lineage of differentiated blood cells. Stem cells reside in a highly specialized microenvironment with surrounding supporting cells, forming a complex and dynamic network to preserve and maintain their function. The survival, activation, and quiescence of stem cells are largely influenced by niche-derived signals, with aging niche contributing to a decline in stem cell function. Although the role of niche in regulating hematopoiesis has long been established by transplantation studies, limited methods in observing the process in vivo have eluded a detailed understanding of the various niche components. Danio rerio (zebrafish) has emerged as a solution in the past few decades, enabling discovery of cellular interactions, in addition to chemical and genetic factors regulating HSCs. This review reiterates zebrafish as a suitable model for studies on vertebrate embryonic and adult hematopoiesis, delving into this temporally and spatially dissected multi-step process. The critical role played by epigenetic regulators are discussed, along with contributions of the various physiological processes in sustaining the stem cell population. Stem cell niche transcends mere knowledge acquisition, assuring scope in cell therapy, organoid cultures, aging research, and clinical applications including bone marrow transplantation and cancer. A better understanding of the various niche components could also leverage therapeutic efforts to drive differentiation of HSCs from pluripotent progenitors, sustain stemness in laboratory cultures, and improve stem cell transplantation outcomes.</p>","PeriodicalId":21955,"journal":{"name":"Stem Cell Reviews and Reports","volume":" ","pages":"605-628"},"PeriodicalIF":4.5,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142955434","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Quality and Regulatory Requirements for the Manufacture of Master Cell Banks of Clinical Grade iPSCs: The EU and USA Perspectives.","authors":"Fernando Martins, Maria H L Ribeiro","doi":"10.1007/s12015-024-10838-9","DOIUrl":"10.1007/s12015-024-10838-9","url":null,"abstract":"<p><p>The discovery of induced pluripotent stem cells (iPSCs) and protocols for their differentiation into various cell types have revolutionized the field of tissue engineering and regenerative medicine. Developing manufacturing guidelines for safe and GMP-compliant final products has become essential. Allogeneic iPSCs-derived cell therapies are now the preferred manufacturing alternative. This option requires the establishment of clinical-grade master cell banks of iPSCs. This study aimed at reviewing the Quality and Regulatory requirements from the two main authorities in the world-Europe (EMA) and the United States (FDA)-regarding the manufacture of clinical grade master cell banks (iPSCs). The minimum requirements for iPSCs to be used in first-in-human clinical trials were also reviewed, as well as current best practices currently followed by iPSC bank manufacturers for final product characterisation. The methodology used for this work was a review of various sources of information ranging from scientific literature, published guidance documents available on the EMA and FDA websites, GMP and ICH guidelines, and applicable compendial monographs. Manufacturers of iPSCs cell banks looking to qualify them for clinical use are turning to the ICH guidelines and trying to adapt their requirements. Specifically with the impact of the field of iPSC cell banks, the following areas should be subject to guidance and harmonisation: i) expression vectors authorized for iPSC generation; ii) minimum identity testing; iii) minimum purity testing (including adventitious agent testing); and iv) stability testing. Current ICH guidelines for biotechnological/biological products should be extended to cover cell banks used for cell therapies.</p>","PeriodicalId":21955,"journal":{"name":"Stem Cell Reviews and Reports","volume":" ","pages":"645-679"},"PeriodicalIF":4.5,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143011929","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"hUC-MSCs Prevent Acute High-Altitude Injury through Apoe/Pdgf-b/p-Erk1/2 Axis in Mice.","authors":"Siyu Yan, Youkun Bi, Qun Liu, Shaole Song, Lihong Ma, Guangju Ji","doi":"10.1007/s12015-024-10840-1","DOIUrl":"10.1007/s12015-024-10840-1","url":null,"abstract":"<p><strong>Background: </strong>The hypobaric hypoxic atmosphere can cause adverse reactions or sickness. The purpose of this study was to explore the preventive effect and mechanism of human umbilical cord mesenchymal stem cells (hUC-MSCs) on acute pathological injury in mice exposed to high-altitude.</p><p><strong>Methods: </strong>We pretreated C57BL/6 mice with hUC-MSCs via the tail vein injection, and then the mice were subjected to hypobaric hypoxic conditions for five days. The effects of hUC-MSCs on the pathological injury of lung, heart, brain were assessed by biochemical analysis, histopathological testing, quantitative real-time polymerase chain reaction (qPCR), and western blot (WB). Further, transcriptome sequencing was used to screen for the potential therapeutic targets of hUC-MSCs in acute pathological injury, the identified signaling axis was characterized using Apoe^-/- mice, qPCR and WB.</p><p><strong>Results: </strong>hUC-MSCs administration notably prevented and relieved gastrointestinal symptoms and inflammation of lung and heart, increased blood oxygen saturation and serum superoxide dismutase (SOD) level, decreased serum malondialdehyde (MDA) level, rescued lung tissue injury and myocardial mitochondrial disorder, elevated nissl bodies number in brain tissue and reduced the degree of pulmonary and cerebral edema. Furthermore, hUC-MSCs pretreatment reversed the down-regulated Apoe and up-regulated Pdgf-b and p-Erk1/2 in the lung of hypobaric hypoxic mice. Thus, hUC-MSCs protected against acute pathological injury caused by hypobaric hypoxic condition via the Apoe/Pdgf-b/p-Erk1/2 axis, and the identified pathway was confirmed by the negative results of Apoe^-/- mice.</p><p><strong>Conclusion: </strong>hUC-MSCs possess the preventive effect on acute pathological injury caused by hypobaric hypoxia environment at high-altitude.</p>","PeriodicalId":21955,"journal":{"name":"Stem Cell Reviews and Reports","volume":" ","pages":"834-848"},"PeriodicalIF":4.5,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143053545","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Empagliflozin Reduces High Glucose-Induced Cardiomyopathy in hiPSC-Derived Cardiomyocytes : Glucose-induced Lipotoxicity in hiPSC-Derived Cardiomyocytes.","authors":"Hsiu-Hui Tsai, Fu-Chih Hsiao, Alice L Yu, Jyuhn-Huarng Juang, John Yu, Pao-Hsien Chu","doi":"10.1007/s12015-024-10839-8","DOIUrl":"10.1007/s12015-024-10839-8","url":null,"abstract":"<p><p>Human-induced pluripotent stem cell (hiPSC) technology has been applied in pathogenesis studies, drug screening, tissue engineering, and stem cell therapy, and patient-specific hiPSC-derived cardiomyocytes (hiPSC-CMs) have shown promise in disease modeling, including diabetic cardiomyopathy. High glucose (HG) treatment induces lipotoxicity in hiPSC-CMs, as evidenced by changes in cell size, beating rate, calcium handling, and lipid accumulation. Empagliflozin, an SGLT2 inhibitor, effectively mitigates the hypertrophic changes, abnormal calcium handling, and contractility impairment induced by HG. Glucose concentration influences SGLT2 expression in cardiomyocytes, highlighting its potential role in diabetic cardiomyopathy. These findings support the potential utility of hiPSC-CMs in studying diabetic cardiomyopathy and the efficacy of empagliflozin in ameliorating HG-induced cardiomyocyte dysfunction. Such research may advance developments in precision medicine and therapeutic interventions for patients with diabetic cardiomyopathy.</p>","PeriodicalId":21955,"journal":{"name":"Stem Cell Reviews and Reports","volume":" ","pages":"849-858"},"PeriodicalIF":4.5,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143011926","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"UTF1 Expression is Important for the Generation and Maintenance of Human iPSCs.","authors":"Khyati Raina, Kirti Modak, Chitra Premkumar, Gaurav Joshi, Dhavapriya Palani, Krittika Nandy, Yazhini Sivamani, Shaji R Velayudhan, Rajkumar P Thummer","doi":"10.1007/s12015-024-10836-x","DOIUrl":"10.1007/s12015-024-10836-x","url":null,"abstract":"<p><strong>Background: </strong>Undifferentiated embryonic cell transcription factor 1 (UTF1) is predominantly expressed in pluripotent stem cells and plays a vital role in embryonic development and pluripotency maintenance. Despite its established importance in murine models, the role of UTF1 on human induced pluripotent stem cells (iPSCs) has not been comprehensively studied.</p><p><strong>Methods: </strong>This study utilized CRISPR/Cas9 gene editing to create UTF1 knockout in human fibroblasts and iPSCs. We employed episomal vectors for reprogramming UTF1 knockout fibroblasts into iPSCs and analyzed the effects of UTF1 depletion on cellular morphology, pluripotency, and viability through Western blotting, PCR, and flow cytometry. In addition, we integrated an shRNA that downregulated the expression of UTF1 for mechanistic studies to understand the impact of UTF1 depletion in iPSC pluripotency and differentiation.</p><p><strong>Results: </strong>UTF1 knockout resulted in significantly reduced reprogramming efficiency and increased spontaneous differentiation, indicating its crucial role in maintaining human iPSC identity and stability. In knockdown experiments, gradual loss of UTF1 led to change in cellular morphologies and decreased expression of core pluripotency markers OCT4 and SOX2. Interestingly, unlike complete UTF1 knockout, the gradual downregulation of UTF1 in iPSCs did not result in apoptosis, suggesting that the loss of pluripotency can occur independently of the apoptotic pathways.</p><p><strong>Conclusions: </strong>UTF1 is essential for maintaining the pluripotency and viability of human iPSCs. Its depletion affects the fundamental properties of stem cells, underscoring the potential challenges in using UTF1-deficient cells for therapeutic applications. Future studies should explore the mechanistic pathways through which UTF1 controls pluripotency and differentiation, which could provide insights into improving iPSC stability for clinical applications.</p>","PeriodicalId":21955,"journal":{"name":"Stem Cell Reviews and Reports","volume":" ","pages":"859-871"},"PeriodicalIF":4.5,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142928236","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Adapted Exosomes for Addressing Chemotherapy-induced Premature Ovarian Insufficiency.","authors":"Mohammad Mousaei Ghasroldasht, Hang-Soo Park, Farzana Liakath Ali, Analea Beckman, Mahya Mohammadi, Nina Hafner, Ayman Al-Hendy","doi":"10.1007/s12015-024-10820-5","DOIUrl":"10.1007/s12015-024-10820-5","url":null,"abstract":"<p><strong>Background: </strong>Premature ovarian insufficiency (POI) presents a multifaceted challenge with limited treatment options. This study explored the therapeutic potential of exosome-based interventions for chemotherapy-induced POI.</p><p><strong>Methods: </strong>Adapted exosomes were engineered from umbilical cord mesenchymal stem cells (UC-MSCs) under a specific co-culture system and used for treating in vitro and in vivo models of chemotherapy-induced premature ovarian insufficiency.</p><p><strong>Results: </strong>In vitro models revealed the significant impact of adapted exosomes, which promoted granulosa cell proliferation, decrease apoptosis, and enhanced ovarian functional markers. The findings in an in vivo chemotherapy-induced POI mouse model indicated the restoration of ovarian morphology, follicle numbers, and fertility in both the naïve and adapted exosome-treated groups. Notably, the adapted exosome group demonstrated a heightened pregnancy rate, increased numbers of primary follicles, and a significant reduction in ovarian apoptosis. MiRNA profiling revealed distinctive cargo in the adapted exosomes, among which miR-20b-5p played a pivotal role in regulating apoptosis and inflammation; this finding is especially important given that apoptosis is one of the primary complications of chemotherapy-induced POI. Furthermore, cells treated with adapted exosomes demonstrated significant overexpression of miR-20b-5p, resulting in decreased PTEN expression and the activation of the PI3K-AKT pathway-a crucial mechanism in mitigating chemotherapy-induced POI.</p><p><strong>Conclusions: </strong>This study introduces an exosome-based therapeutic approach, emphasizing the importance of exosome cargo composition in treating disorders. Further investigation into the identified miRNA profile in adapted exosomes is necessary to clarify the underlying mechanisms, potentially leading to the development of a new treatment for clinical premature ovarian insufficiency.</p>","PeriodicalId":21955,"journal":{"name":"Stem Cell Reviews and Reports","volume":" ","pages":"779-796"},"PeriodicalIF":4.5,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143374864","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Development and Applications of Organoids in Gynecological Diseases.","authors":"Jian Yang, Wenwen Li, Zihan Zhang, Zhonglei Xu, Wenjing Zhu, Jing Wang, Wenyan Wang","doi":"10.1007/s12015-024-10833-0","DOIUrl":"10.1007/s12015-024-10833-0","url":null,"abstract":"<p><p>Organoids are rapidly self-organizing 3D in vitro cultures derived from pluripotent stem cells (PSCs) or adult stem cells (ASCs) that possess disease-like characteristics with high success rates. Due to their ability to retain tissue structure, biological phenotypes, and genetic information, they have been utilized as a novel in vitro model for disease research. In recent years, scientists have established self-organizing 3D organoids for human endometrium, fallopian tubes, ovaries, and cervix by culturing stem cells with cytokines in 3D scaffolds. The integration of organoids with animal models, organ-on-a-chip systems, and 3D printing technologies offers a novel preclinical model for exploring disease mechanisms and developing treatments. This review elaborate on the recent research progress of stem cells-formed organoids in the field of gynecology from the aspects of constructing gynecological disease organoids, drug screening and new drug development, simulation modeling, allogeneic transplantation, regenerative medicine and personalized treatment.\"</p>","PeriodicalId":21955,"journal":{"name":"Stem Cell Reviews and Reports","volume":" ","pages":"629-644"},"PeriodicalIF":4.5,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142814394","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Elevating Dermatology Beyond Aesthetics: Perinatal-Derived Advancements for Rejuvenation, Alopecia Strategies, Scar Therapies, and Progressive Wound Healing.","authors":"Mohammad Amin Khalilzad, Javad Mohammadi, Soumayeh Amirsaadat, Sajad Najafi, Sona Zare, Mohammad Ali Nilforoushzadeh, Mitra Khalilzad, Ayoub Khaghani, Mohammad Reza Fayyazi Soltankouhi, Alireza Hajimohammad","doi":"10.1007/s12015-024-10835-y","DOIUrl":"10.1007/s12015-024-10835-y","url":null,"abstract":"<p><p>Dermatologists have been interested in recent advancements in regenerative therapy. Current research is actively investigating the possibility of placental tissue derivatives to decelerate the skin aging process, enhance skin regeneration, reduce scarring, and prevent hair loss. Amniotic membranes (AM) play a crucial role in regenerative medicine as they serve as a suitable means of transporting stem cells, growth hormones, cytokines, and other essential compounds. Regulating an intricate network of biological processes improves the development and repair of tissues. Studies done by dermatologists indicate that several compounds found in the decidua, umbilical cord, and amniotic membrane have the potential to be used for regeneration. Examples include mesenchymal stem cells, growth factors, and immunomodulatory pharmaceuticals. Due to research and technological developments, scientists may use placental sections to facilitate skin regeneration, minimize scarring, and expedite wound healing. This study examines the current state of dermatological therapy, with a focus on using derivatives obtained from fetal tissue as the basis. The critical areas of study focus on this strategy are the potential benefits, growth opportunities, and recovery rates. Based on a thorough examination of the available literature and clinical data, we want to make definitive conclusions on the possible influence of fetal tissue derivatives in dermatological therapy.</p>","PeriodicalId":21955,"journal":{"name":"Stem Cell Reviews and Reports","volume":" ","pages":"709-729"},"PeriodicalIF":4.5,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142972195","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Optimization of Transcription Factor-Driven Neuronal Differentiation from Human Induced Pluripotent Stem Cells for Disease Modelling and Drug Screening.","authors":"Martina Servetti, Martino Caramia, Giulia Parodi, Fabrizio Loiacono, Ennio Nano, Giorgia Biddau, Lorenzo Ferrando, Lisastella Morinelli, Pierluigi Valente, Sergio Martinoia, Andrea Escelsior, Gianluca Serafini, Serena Tamburro, Simona Baldassari, Anna Fassio, Fabio Benfenati, Anna Corradi, Bruno Sterlini","doi":"10.1007/s12015-025-10845-4","DOIUrl":"10.1007/s12015-025-10845-4","url":null,"abstract":"<p><p>Progress of human brain in vitro models stands as a keystone in neurological and psychiatric research, addressing the limitations posed by species-specific differences in animal models. The generation of human neurons from induced pluripotent stem cells (iPSCs) using transcription factor reprogramming protocols has been shown to reduce heterogeneity and improve consistency across different stem cell lines. Despite notable advancements, the current protocols still exhibit several shortcomings. This study focuses on standardizing and optimizing the procedure for iPSC-derived glutamatergic neurons generation through the inducible overexpression of Neurogenin-2. Noteworthy refinements include stringent scrutiny of genomic rearrangements post-fibroblast reprogramming, selection of a homogeneously integrated NGN2-cassettes population, and the incorporation of an intermediate step during neuronal differentiation to store neuronal progenitors. The neural culture showed a high degree of neuronal maturation and consistency, as shown by single-cell and network electrophysiological recordings. These advancements aim to provide more reliable tools for disease modelling and drug screening in neurological disorders.</p>","PeriodicalId":21955,"journal":{"name":"Stem Cell Reviews and Reports","volume":" ","pages":"816-833"},"PeriodicalIF":4.5,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143067202","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Stem Cell Markers LGR5, LGR4 and Their Immediate Signalling Partners are Dysregulated in Preeclampsia.","authors":"Georgia P Wong, Sunhild Hartmann, Olivia Nonn, Ping Cannon, Tuong-Vi Nguyen, Manju Kandel, Natasha de Alwis, Ciara N Murphy, Natasha Pritchard, Ralf Dechend, Natalie J Hannan, Stephen Tong, David G Simmons, Tu'uhevaha J Kaitu'u-Lino","doi":"10.1007/s12015-024-10831-2","DOIUrl":"10.1007/s12015-024-10831-2","url":null,"abstract":"<p><p>Leucine-rich repeat-containing G protein-coupled receptors 5/4 (LGR5/LGR4) are critical stem cell markers in epithelial tissues including intestine. They agonise wingless-related integration site (WNT) signalling. Until now, LGR5/LGR4 were uncharacterised in placenta, where analogous functions may exist. We characterised LGR5/LGR4, their ligands/targets in human placenta, with further assessments on dysregulation in preeclampsia/fetal growth restriction (FGR). LGR5 mRNA was unaltered in first trimester (n = 11), preterm (n = 9) and term (n = 11) placental lysate. LGR5 was enriched in human trophoblast stem cells (hTSCs) and downregulated with differentiation to extravillous trophoblasts (p < 0.0215) and syncytiotrophoblasts (p < 0.0350). In situ hybridisation localised LGR5 to unique, proliferative MKI67 + mononuclear trophoblasts underlying syncytium which concurred with proposed progenitor identities in single-cell transcriptomics. LGR5 expression was significantly reduced in placentas from early-onset preeclampsia (p < 0.0001, n = 81 versus n = 19 controls), late-onset preeclampsia (p = 0.0046, n = 20 versus n = 33 controls) and FGR (p = 0.0031, n = 34 versus n = 17 controls). LGR4 was elevated in first trimester versus preterm and term placentas (p = 0.0412), in placentas with early-onset preeclampsia (p = 0.0148) and in FGR (p = 0.0417). Transcriptomic analysis and in vitro hTSC differentiation to both trophoblast lineages suggested LGR4 increases with differentiation. Single-nucleus RNA sequencing of placental villous samples supported LGR5 and LGR4 localisation findings. Hypoxia/proinflammatory cytokine treatment modelling elements experienced by the placenta in placental insufficiency pathogenesis did not significantly alter LGR5/LGR4. Ligands R-spondins 1/3/4, and neutralising targets ring finger protein 43 (RNF43) and zinc and ring finger 3 (ZNRF3) were also reduced in placentas from preeclamptic pregnancies. This study is the first to describe LGR5/LGR4 and their signalling partner expression in human placenta. Their dysregulations in the preeclamptic placenta allude to disruptions to integral trophoblast stem cell function/differentiation that may occur during placental development related to WNT signalling.</p>","PeriodicalId":21955,"journal":{"name":"Stem Cell Reviews and Reports","volume":" ","pages":"872-896"},"PeriodicalIF":4.5,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142839902","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}