Stem Cell Reviews and Reports最新文献

{"title":"Hematopoietic Stem Cell Fates and the Cellular Hierarchy of Mammalian Hematopoiesis: from Transplantation Models to New Insights from in Situ Analyses.","authors":"Dania Shaban, Nay Najm, Lucie Droin, Anastasia Nijnik","doi":"10.1007/s12015-024-10782-8","DOIUrl":"10.1007/s12015-024-10782-8","url":null,"abstract":"<p><p>Hematopoiesis is the process that generates the cells of the blood and immune system from hematopoietic stem and progenitor cells (HSPCs) and represents the system with the most rapid cell turnover in a mammalian organism. HSPC differentiation trajectories, their underlying molecular mechanisms, and their dysfunctions in hematologic disorders are the focal research questions of experimental hematology. While HSPC transplantations in murine models are the traditional tool in this research field, recent advances in genome editing and next generation sequencing resulted in the development of many fundamentally new approaches for the analyses of mammalian hematopoiesis in situ and at single cell resolution. The current review will cover many recent developments in this field in murine models, from the bulk lineage tracing studies of HSPC differentiation to the barcoding of individual HSPCs with Cre-recombinase, Sleeping Beauty transposase, or CRISPR/Cas9 tools, to map hematopoietic cell fates, together with their transcriptional and epigenetic states. We also address studies of the clonal dynamics of human hematopoiesis, from the tracing of HSPC clonal behaviours based on viral integration sites in gene therapy patients to the recent analyses of unperturbed human hematopoiesis based on naturally accrued mutations in either nuclear or mitochondrial genomes. Such studies are revolutionizing our understanding of HSPC biology and hematopoiesis both under homeostatic conditions and in the response to various forms of physiological stress, reveal the mechanisms responsible for the decline of hematopoietic function with age, and in the future may advance the understanding and management of the diverse disorders of hematopoiesis.</p>","PeriodicalId":21955,"journal":{"name":"Stem Cell Reviews and Reports","volume":" ","pages":"28-44"},"PeriodicalIF":4.5,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142112157","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":"https://doi.org/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":""},"PeriodicalIF":4.5,"publicationDate":"2024-12-17","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}

{"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":"https://doi.org/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":""},"PeriodicalIF":4.5,"publicationDate":"2024-12-12","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":"Alveolar Bone Tissue Engineering Using Deciduous Dental Pulp Stem Cells in a Patient with Cleft Lip and Palate.","authors":"Isabella Fernandes Carvalho, Brenda Santos Veloso, José Ferreira da Cunha Filho, Samara Kelly da Silva Cavalcante, Milena Regia Sousa Ferreira, Maysa Luna de Souza, Daniela Franco Bueno","doi":"10.1007/s12015-024-10832-1","DOIUrl":"https://doi.org/10.1007/s12015-024-10832-1","url":null,"abstract":"<p><p>The use of tissue bioengineering strategies in dentistry has gained relevance. Many studies indicate that stem cells associated with biomaterials can regenerate intraoral tissues and have been applied to patients with cleft lip and palate (CLP). One of the treatments is alveolar bone reconstruction through bone grafts, where the bone is removed from the donor site and placed in the alveolar cleft. The use of stem cells from deciduous dental pulp, associated with a hydroxyapatite and collagen scaffold, can eliminate the need for autologous bone grafts, reducing pain and morbidity at the donor site. This study presents a case report in which a patient with cleft lip and palate was treated using this technique, resulting in complete filling of the alveolar cleft after 12 months.</p>","PeriodicalId":21955,"journal":{"name":"Stem Cell Reviews and Reports","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2024-12-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142786712","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":"Antifragile Treatment for Efficient Chimerism of Induced Pluripotent Stem Cells Derived Hematopoietic Stem Cells.","authors":"Daekee Kwon, Taewook Lee, Mijung Han, So-Woon Han, Kyung-Sun Kang","doi":"10.1007/s12015-024-10828-x","DOIUrl":"https://doi.org/10.1007/s12015-024-10828-x","url":null,"abstract":"<p><p>Engraftable hematopoietic stem cells (HSC) can be obtained from bone marrow, umbilical cord blood, and peripheral blood (PB). However, a major bottleneck in HSC transplantation is identifying an unrelated donor that completely matches the human leukocyte antigen type of the recipient. This issue can be resolved by producing patient-specific stem cells. The purpose of this study was to identify the conditions under which induced pluripotent stem cells (iPSC)-derived hematopoietic stem cells (iHSC) exhibit high efficiency. Because HSC are fragile and vulnerable to damage, this study was performed under the hypothesis that the engraftment rate could be increased by antifragile treatment. Antioxidant ginsenoside Rg1 was used to differentiate from iPSC to iHSC, and differentiated iHSC was intravenously injected into Balb/c nude mouse conditioned with diverse concentrations of busulfan. Engraftment was verified by the presence of human-specific markers in the PB at 2 and 8 weeks post iHSC transplantation. iHSC differentiated by incorporating 1 µM of Rg1 demonstrated high colony forming efficiency in vitro. Additionally, high efficiency engraftment occurred immediately after iHSC were transplanted into mice conditioned with high dose busulfan at a dosage of 125 mg/kg or higher. In this study, high-quality iHSC manufacturing and transplantation conditions capable of high efficiency engraftment in vivo were established. Hereafter, this method of producing HSC using patient-specific iPSC will become the fourth new source of HSC. Additionally, if gene-editing technology is applied, the scope of its application can be expanded to diverse infectious diseases.</p>","PeriodicalId":21955,"journal":{"name":"Stem Cell Reviews and Reports","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2024-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142786713","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":"Human Umbilical Cord Mesenchymal Stem Cell-Derived Exosomes Loaded Mir-29-3p Targets AhR to Improve Juvenile Idiopathic Arthritis via Inhibiting the Expression of IL-22 in CD4⁺ T Cell.","authors":"Xinyi Wei, Kunpeng Sui, Yuanyuan Peng, Sha Li, Yu Fang, Zhi Chen, Xiao Du, Xue Xie, Haiming Tang, QiuYue Wen, JingWei Li, Meilin He, Qin Cheng, Wei Zhang","doi":"10.1007/s12015-024-10827-y","DOIUrl":"https://doi.org/10.1007/s12015-024-10827-y","url":null,"abstract":"<p><strong>Background: </strong>Juvenile idiopathic arthritis (JIA) is one of the most common chronic inflammatory rheumatic diseases in children. Human umbilical cord mesenchymal stem cells (HUCMSCs)-derived exosomes (HUCMSCs-Exos) are involved in autoimmune diseases. This study investigates the mechanism of HUCMSC-Exos in improving JIA by targeting AhR through delivery of miR-29-3p to inhibit IL-22 expression in CD4⁺ T cells.</p><p><strong>Methods: </strong>Collagen induced arthritis (CIA) mouse model was established, and mice were treated with HUCMSCs-Exos and miR-29-3p antagomir, respectively. CD4⁺ T cells from JIA patients were used for cell experiments. The mechanism was elucidated by histopathological staining, transmission electron microscopy (TEM), immunohistochemistry, CCK-8 assay, flow cytometry, Western blotting, real-time PCR, and enzyme-linked immunosorbent assay (ELISA), laser confocal microscopy, and luciferase assay.</p><p><strong>Result: </strong>JIA-CD4⁺ T cells showed higher expression of IL-22 and lower the levels of miR-29-3p, while HUCMSCs-Exos significantly inhibited the expression of IL-22 and increased the levels of miR-29a-3p, miR-29b-3p, and miR-29c-3p in CD4⁺ T cells from JIA patients. The expression of miR-29a-3p, miR-29b-3p, miR-29c-3p, AhR, and IL-22 in CD4⁺ T cells was significantly reversed when co-cultured with HUCMSCs transfected with miR-29-3p mimic or miR-29-3p inhibitor. In vivo experiment, HUCMSCs-Exos ameliorated CIA mice by delivering miR-29-3p to inhibit AhR, IL-22, IL-22R1, MMP3, and MMP13 expression. Furthermore, HUCMSCs-Exos also deliver miR-29-3p targeting AhR expression to inhibit IL-22 in JIA-CD4 + T cells through alleviating arthritic synovial fibroblast activation.</p><p><strong>Conclusion: </strong>HUCMSCs-Exos loaded miR-29-3p targets AhR to improve JIA via inhibiting the expression of IL-22 in CD4⁺ T cell, which provides a scientific basis for the treatment of JIA.</p>","PeriodicalId":21955,"journal":{"name":"Stem Cell Reviews and Reports","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2024-12-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142772472","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":"Comparative Evaluation of Endothelial Colony-Forming Cells from Cord and Adult Blood vs. Human Embryonic Stem Cell-Derived Endothelial Cells: Insights into Therapeutic Angiogenesis Potential.","authors":"David M Smadja, Laetitia Mauge, Jeanne Rancic, Pascale Gaussem, Olivier Feraud, Noufissa Oudrhiri, Annelise Bennaceur-Griscelli","doi":"10.1007/s12015-024-10830-3","DOIUrl":"https://doi.org/10.1007/s12015-024-10830-3","url":null,"abstract":"<p><p>The discovery of endothelial progenitor cells has revolutionized our understanding of postnatal blood vessel formation, with endothelial colony-forming cells (ECFCs) emerging as key players in vasculogenesis. Among various ECFC sources, cord blood-derived ECFCs (CB-ECFCs) are of particular interest due to their superior proliferative and clonogenic potential and their ability to promote vascular network formation. Human embryonic stem cell-derived endothelial cells (hESC-ECs) have also shown potential in regenerative medicine, though their vasculogenic efficacy remains unclear compared to CB- and adult blood-derived ECFCs (AB-ECFCs). This study aimed to directly compare the angiogenic and vasculogenic capabilities of CB-ECFCs, AB-ECFCs, and hESC-ECs in vitro and in vivo. Our results demonstrated that CB-ECFCs had a significantly higher proliferation rate than both AB-ECFCs and hESC-ECs (p < 0.01). In tube formation assays, CB-ECFCs exhibited superior ability to form capillary-like structures compared to hESC-ECs (p < 0.0001) and AB-ECFCs (p < 0.01). In vivo, CB-ECFCs significantly improved blood flow recovery in ischemic tissue (p < 0.01), outperforming both AB-ECFCs and hESC-ECs, with no significant recovery observed in the latter two groups. These findings suggest that CB-ECFCs represent a more effective cell source for therapeutic angiogenesis, while further optimization is needed to enhance the efficacy of hESC-ECs for clinical applications. Future research should explore the molecular mechanisms underlying the superior regenerative potential of CB-ECFCs and focus on improving the stability and functionality of stem cell-derived ECs for therapeutic use.</p>","PeriodicalId":21955,"journal":{"name":"Stem Cell Reviews and Reports","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2024-11-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142751718","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":"Erroneous Differentiation of Tendon Stem/Progenitor Cells in the Pathogenesis of Tendinopathy: Current Evidence and Future Perspectives.","authors":"Yucheng Gao, Hao Wang, Liu Shi, Panpan Lu, Guangchun Dai, Ming Zhang, Bowen Han, Mumin Cao, Yingjuan Li, Yunfeng Rui","doi":"10.1007/s12015-024-10826-z","DOIUrl":"https://doi.org/10.1007/s12015-024-10826-z","url":null,"abstract":"<p><p>Tendinopathy is a condition characterized by persistent tendon pain, structural damage, and compromised functionality. Presently, the treatment for tendinopathy remains a formidable challenge, partly because of its unclear pathogenesis. Tendon stem/progenitor cells (TSPCs) are essential for tendon homeostasis, regeneration, remodeling, and repair. An innovative theory has been previously proposed, with insufficient evidence, that the erroneous differentiation of TSPCs may constitute one of the fundamental mechanisms underpinning tendinopathy. Over the past few years, there has been accumulating evidence for plausibility of this theory. In this review, we delve into alterations in the differentiation potential of TSPCs and the underlying mechanisms in the context of injury-induced tendinopathy, diabetic tendinopathy, and age-related tendinopathy to provide updated evidence on the erroneous differentiation theory. Despite certain limitations inherent in the existing body of evidence, the erroneous differentiation theory emerges as a promising and highly pertinent avenue for understanding tendinopathy. In the future, advanced methodologies will be harnessed to further deepen comprehension of this theory, paving the way for prospective developments in clinical therapies targeting TSPCs for the management of tendinopathy.</p>","PeriodicalId":21955,"journal":{"name":"Stem Cell Reviews and Reports","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2024-11-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142695458","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":"HucMSCs-derived Exosomes Promote Lung Development in Premature Birth via Wnt5a/ROCK1 Axis.","authors":"Xin Li, Lidong Huang, Min Mao, Hong Xu, Caijun Liu, Yang Liu, Hanmin Liu","doi":"10.1007/s12015-024-10824-1","DOIUrl":"https://doi.org/10.1007/s12015-024-10824-1","url":null,"abstract":"<p><p>Bronchopulmonary dysplasia (BPD) frequently affects extremely preterm and low birth weight infants, with current treatments lacking specificity. Enhancing extra-uterine preterm alveoli development and repairing damage are crucial for BPD management. Here we show that exosomes derived from human umbilical cord mesenchymal stem cells (hucMSCs-Exos) can enhance fetal lung development in mice by delivering specific contents. Briefly, hucMSCs-Exos were extracted using ultracentrifugation and identified by transmission electron microscopy (TEM), flow cytometry, Western blot (WB), and nanoparticle tracking analysis (NTA). These exosomes were then administered to pregnant mice via tail vein injection. Embryonic lung tissues were collected at E13.5 and E18.5 via cesarean section and analyzed using hematoxylin-eosin (HE) staining, immunofluorescence, and TEM. Proteomic analysis was conducted to identify protein components in the exosomes, and WB was used to assess protein expression changes. hucMSCs-Exos from full-term infants were more effective in promoting cell proliferation than those from preterm infants. In vivo, full-term hucMSCs-Exos significantly enhanced alveolarization in fetal lung tissues. Proteomic analysis revealed higher Wnt5a expression in full-term hucMSCs-Exos, and further experiments confirmed a direct interaction between Wnt5a and ROCK1. WB also showed increased expression of the autophagy marker LC3B in the lung tissues of mice treated with full-term exosomes. In conclusion, term hucMSCs-Exos may directly regulate the phosphorylation of ROCK1 in mouse lung tissue through naturally enriched Wnt5a, thus promoting autophagy of AT2 cells and lamellar body development, and ultimately enhance the alveolarization and reducing the incidence of BPD in premature infants.</p>","PeriodicalId":21955,"journal":{"name":"Stem Cell Reviews and Reports","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2024-11-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142676820","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":"LNK/SH2B3 Loss Exacerbates the Development of Myeloproliferative Neoplasms in CBL-deficient Mice.","authors":"Yafei Chen, Shangyu Gong, Juan Tang, Xinying Wang, Yudan Gao, Hanying Yang, Wanze Chen, Hailiang Hu, Wei Tong, Kaosheng Lv","doi":"10.1007/s12015-024-10825-0","DOIUrl":"10.1007/s12015-024-10825-0","url":null,"abstract":"<p><p>Genetic variations of signaling modulator protein LNK (also called SH2B3) are associated with relatively mild myeloproliferative phenotypes in patients with myeloproliferative neoplasms (MPN). However, these variations can induce more severe MPN disease and even leukemic transformation when co-existing with other driver mutations. In addition to the most prevalent driver mutation JAK2V617F, LNK mutations have been clinically identified in patients harboring CBL inactivation mutations, but its significance remains unclear. Here, using a transgenic mouse model, we demonstrated that mice with the loss of both Lnk and Cbl exhibited severe splenomegaly, extramedullary hematopoiesis and exacerbated myeloproliferative characteristics. Moreover, a population of Mac1⁺ myeloid cells expressed c-Kit in aged mice. Mechanistically, we discovered that LNK could pull down multiple regulatory subunits of the proteosome. Further analysis confirmed a positive role of LNK in regulating proteasome activity, independent of its well-established function in signaling transduction. Thus, our work reveals a novel function of LNK in coordinating with the E3 ligase CBL to regulate myeloid malignancies.</p>","PeriodicalId":21955,"journal":{"name":"Stem Cell Reviews and Reports","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2024-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142669204","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}