Cells Tissues Organs最新文献

{"title":"Rapid, Growth Factor-Reduced Induction of Functional Neurons from hiPSCs.","authors":"Natalie A Parker, Oluwadamilola E Kolawole, Zhixin Liao, Farsin S Syed, Kara E Moquin, Nisha R Iyer","doi":"10.1159/000552324","DOIUrl":"https://doi.org/10.1159/000552324","url":null,"abstract":"<p><strong>Introduction: </strong>Human induced pluripotent stem cells (hiPSCs) can be rapidly converted into neurons via Neurogenin-2 (NGN2) overexpression, but many protocols require costly reagents during the initial induction phase that may limit adoption by labs without routine neuronal differentiation experience. We developed a simplified, low-cost protocol using a tetracycline-inducible (TET-on) NGN2 system in minimal media to generate cortical neurons in as few as 6 days.</p><p><strong>Methods: </strong>KOLF2.1J hiPSCs were stably transfected with a TET-on NGN2 cassette using the nonviral PiggyBac system and induced with doxycycline in Essential 6 media with or without the Notch inhibitor DAPT. Neurogenesis was evaluated with immunocytochemistry (ICC) and RT-qPCR, and cultures matured in defined conditions were characterized by multielectrode array (MEA) recordings to assess functional maturation.</p><p><strong>Results: </strong>DAPT markedly improved hiPSC-to-neuron conversion efficiency, and yielded glutamatergic neurons expressing cortical markers. MEA recordings showed spontaneous activity by day 14 and synchronous network firing by day 35. Secondary PB transfection enabled Td-Tomato labelling of KOLF2.1J:pB-TO-NGN2 hiPSCs, allowing 24-hour live imaging of neurite outgrowth.</p><p><strong>Conclusion: </strong>This streamlined, growth-factor-free workflow provides an accessible route for generating functional neurons from patient-derived hiPSCs, including in labs with limited hiPSC or neuronal culture experience.</p>","PeriodicalId":9717,"journal":{"name":"Cells Tissues Organs","volume":" ","pages":"1-18"},"PeriodicalIF":1.9,"publicationDate":"2026-05-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147834211","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mechanisms of cell plasticity during injury-induced epithelial reprogramming.","authors":"Evelyn Mazzarelli, Sara Lovisa","doi":"10.1159/000552260","DOIUrl":"https://doi.org/10.1159/000552260","url":null,"abstract":"<p><strong>Background: </strong>Plasticity defines the capacity to change identity in response to stimuli and represents a property intrinsically inherited from embryonic development. The homeostatic epithelial turnover of many organs is guaranteed by plasticity events where stem cell progenitors generate mature differentiated epithelial cells. Plasticity is also a major hallmark of cancer cells particularly with respect to their ability to escape treatment sensitivity and adapt to harsh microenvironment.</p><p><strong>Summary: </strong>In the context of tissue injury, modifications of epithelial cell identity represent a fundamental hallmark of damage-induced repair and regenerative processes. Epithelial reprogramming may occur through activation of dedifferentiation programs including fetal reversion and paligenosis, as well as through switches in lineage commitment, such as in transdetermination and transcommitment. Additional mechanisms rely on trans-differentiation processes between different mature epithelial cell types without the involvement of adult stem cells. The activation of all these plastic events supporting epithelial regeneration occurs not only at the phenotypic level but importantly involve epigenetic control, metabolic rearrangements and external sensing.</p><p><strong>Key messages: </strong>Here we present and discuss the most recent evidences highlighting the multiple aspects of epithelial cell plasticity involved in the attempt to support repair and regenerative processes. This review will contribute to better define the broad term of plasticity, especially as emerged from latest investigations employing single-cell based omics, and identify universal and organ-specific mechanisms of injury-induced epithelial reprogramming.</p>","PeriodicalId":9717,"journal":{"name":"Cells Tissues Organs","volume":" ","pages":"1-28"},"PeriodicalIF":1.9,"publicationDate":"2026-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147811429","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Nanofibrous-Composite Hydrogels for Modulating Stem Cell Behavior.","authors":"Andres F Roca-Arroyo, Jhonatan A Gutierrez-Rivera, Laura M Mejia-Rosales, Logan D Morton, David A Castilla-Casadiego","doi":"10.1159/000552028","DOIUrl":"https://doi.org/10.1159/000552028","url":null,"abstract":"<p><strong>Background: </strong>Hydrogels are widely used as ECM-mimetic biomaterials, but most lack the nanofibrous hierarchy of the native extracellular matrix, which is essential for regulating human stem cells (hSCs) behavior. Nanofibrous composite hydrogels address this limitation by incorporating fibrillar cues, either intrinsically formed, dispersed within the matrix, or applied at the surface, to better replicate the structural and mechanotopographical features of the stem cell niche.</p><p><strong>Summary: </strong>This review systematically compares three nanofiber hydrogel architectures: self-assembling nanofiber matrices, hydrogels with encapsulated electrospun fibers, and hydrogels surface-decorated with fibrous coatings. We examine how differences in fiber chemistry, stiffness, degradability, and spatial organization regulate key hSCs' behaviors, including adhesion, viability, morphology, proliferation, migration, differentiation, and secretion. Polymeric, natural, hybrid, magnetic, and bioactive nanoparticle reinforced fibers are each discussed to highlight how each configuration generates distinct biophysical and biochemical cues. By linking fabrication strategies to resulting cellular outcomes, this review outlines architecture-specific advantages and limitations that inform the rational design of next-generation ECM-mimetic scaffolds.</p><p><strong>Key messages: </strong>Nanofibrous hydrogels bridge the gap between conventional hydrogel mechanics and the nanoscale organization of the native ECM, enabling more physiologically relevant control of hSCs' behavior. Each architecture provides distinct structural and mechanobiological cues suited to different therapeutic or manufacturing goals. Hybrid and multifunctional fiber systems, such as magnetic systems, ion-releasing platforms, and nanoparticle-enhanced fibers, deliver synergistic biochemical and mechanical signals that enhance differentiation and paracrine activity. Understanding how fiber properties and organization influence cell responses provides a roadmap for designing ECM-mimetic biomaterials optimized for scalable hSCs expansion and regenerative applications.</p>","PeriodicalId":9717,"journal":{"name":"Cells Tissues Organs","volume":" ","pages":"1-37"},"PeriodicalIF":1.9,"publicationDate":"2026-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147697586","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comparative Analysis of Temperature-Dependent Endocytic Regulation of Notch Signaling in Chick and Mouse Neural Progenitors.","authors":"Kai-Wei Lin, Pei-Rong Wu, Cheng-Chang Chen, Alexander Halim, Bo-Kai Liao, Pei-Shan Hou","doi":"10.1159/000551895","DOIUrl":"https://doi.org/10.1159/000551895","url":null,"abstract":"<p><p>Temperature plays a crucial role in embryonic development, particularly in oviparous species that experience natural fluctuations during incubation. Unlike viviparous embryos developing under stable maternal conditions, chick embryos are exposed to external temperature variability that can influence cellular regulatory processes. Notch signaling, a conserved pathway essential for maintaining the neural progenitor cell (NPC) pool, is regulated by endosomal recycling; however, the mechanism by which temperature modulates this process across species remains poorly understood. To model environmental challenges experienced by chick embryos, we examined the effects of a physiologically relevant low temperature (30°C) on Dll1-mediated Notch signaling in chick and mouse NPCs. Under hypothermic conditions, Dll1 reporter signals increased in chick NPCs but decreased in mouse NPCs, correlating with corresponding changes in Notch activity. Chick NPCs maintained progenitor gene expression at low temperature, whereas mouse NPCs showed reduced expression. Mechanistic analyses revealed that distinct recycling pathways are differentially required for Notch signaling across temperatures and species. Chick NPCs maintained Notch signaling through both fast and slow recycling under normothermia and additional degradation under hypothermia, whereas mouse NPCs relied on slow recycling and degradation under normothermia and showed impaired recycling under hypothermia. Together, these findings reveal species-specific adaptations in the temperature-dependent endocytic regulation of Notch signaling, highlighting how environmental temperature influences the maintenance of neural progenitors across species.</p>","PeriodicalId":9717,"journal":{"name":"Cells Tissues Organs","volume":" ","pages":"1-28"},"PeriodicalIF":1.9,"publicationDate":"2026-04-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147632517","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Retraction Statement.","authors":"","doi":"10.1159/000551163","DOIUrl":"https://doi.org/10.1159/000551163","url":null,"abstract":"<p><p>The article \"IRF9 Affects the TNF-Induced Phenotype of Rheumatoid-Arthritis Fibroblast-Like Synoviocytes via Regulation of the SIRT-1/NF-κB Signaling Pathway\" [Cells Tissues Organs. 2020;209(2-3):110-119; https://doi.org/10.1159/000508405] by Fan Jiang, Hong-Yi Zhou, Li-Fang Zhou, Wei Zeng, and Li-Han Zhao has been retracted by the Publisher and the Editors.After publication of this article, concerns were raised about the integrity of the data presented in Figure 1. Specifically, panels in Figure 1c had previously been published by different author groups representing different experimental conditions.Figure 1c \"control\" panel is the same as Figure 3b panel \"Anti-miR-C FITC-A\" in [1], Figure 3b panel \"NC siRNA\" [2], and Figure 3a panel \"SNORD44\" in [3].Figure 1c \"TNF\" panel is the same as Figure 3a panel \"Anti-miR-C\" in [1].Figure 1c \"TNF + sh-Ctrl\" panel is the same as Figure 3a panel \"Anti-miR-186\" in [1] and Figure 3b panel \"empty vector\" in [3].Figure 1c \"sh-IRF9\" panel is the same as Figure 3b panel \"miR-C FITC-A\" in [1] and Figure 3b panel \"blank\" in [2].Figure 1c \"TNF + sh-IRF9\" panel is the same as Figure 3d panel \"Anti-miR-186 FITC-A\" in [1].Figure 1c \"TNF + sh-SIRT1\" panel is the same as Figure 3a panel \"miR-C FITC-A\" in [1] and Figure 3a panel \"control\" in [3].Figure 1c \"TNF + sh-IRF9 + sh-SIRT1\" panel is the same as Figure 3a panel \"miR-186 FITC-A\" in [1] and Figure 3a panel \"empty vector\" in [3].The authors did not respond to requests to comment on the concerns and provide the raw data within the given timeframe despite multiple attempts of contact. The matter was raised to the corresponding author's institution who did not respond to our request for an investigation. Given the severity of the concerns raised, this article is being retracted. The authors have not responded to our correspondence regarding this retraction despite multiple attempts of contact.</p>","PeriodicalId":9717,"journal":{"name":"Cells Tissues Organs","volume":" ","pages":"1-2"},"PeriodicalIF":1.9,"publicationDate":"2026-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147479688","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Role of Biomaterials in Enhancing Cell Therapy.","authors":"Roaa Hadi, Justin Putman, Jorge Almodovar","doi":"10.1159/000551247","DOIUrl":"10.1159/000551247","url":null,"abstract":"<p><strong>Background: </strong>Cell-based therapies are revolutionizing medicine by offering regenerative and immunomodulatory capabilities beyond traditional treatments. These therapies hold promise for diseases, such as cancer, autoimmune disorders, and diabetes. However, clinical translation is challenged by immune rejection, reduced cell viability, and poor control over therapeutic delivery.</p><p><strong>Summary: </strong>Biomaterials can provide innovative solutions to these barriers by creating supportive environments, enhancing cell survival, and enabling targeted, sustained delivery. This review highlights advances in biomaterial strategies - including lipid and polymeric nanoparticles, hydrogels, fibrous scaffolds, and layer-by-layer assemblies - and their application across T-cell, macrophage, stem cells, and islet cell therapies. Each material class offers unique physicochemical and/or mechanical properties that can be tuned to meet the specific needs of different cell types and therapeutic contexts.</p><p><strong>Key messages: </strong>Biomaterials provide critical tools for enhancing the efficacy and precision of cell-based therapies. Despite substantial progress, challenges remain with selecting the appropriate biomaterial for specific applications and retaining biocompatibility long term. The ongoing development of patient-specific and adaptable biomaterials holds promise for further breakthroughs in regenerative medicine. This review underscores the potential of biomaterials to drive forward the field of cell therapy, opening new avenues for treating a wide range of diseases.</p>","PeriodicalId":9717,"journal":{"name":"Cells Tissues Organs","volume":" ","pages":"1-16"},"PeriodicalIF":1.9,"publicationDate":"2026-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147303059","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Reconstructing Early Human Embryonic Development: From in vitro Models to Multimodal Integration.","authors":"Gang Chen, Zhiyuan Guo, Hongmei Wang, Long Yan","doi":"10.1159/000550960","DOIUrl":"10.1159/000550960","url":null,"abstract":"<p><strong>Background: </strong>Early human embryonic development sets the trajectory for health across the life course. Any aberrations in this process are associated with a heightened burden of adverse pregnancy outcomes. Accordingly, a comprehensive understanding of early human embryogenesis, together with the development of faithful research models, is pivotal for elucidating pregnancy physiology and pathophysiology. However, as embryonic development occurs within the uterus, direct observation has been severely limited by ethical and technical constraints.</p><p><strong>Summary: </strong>To overcome these challenges, in vitro culture (IVC) systems have emerged as powerful platforms for studying early embryonic development under controlled conditions. These systems support human embryo development to the primitive streak anlage stage (near the 14-day ethical boundary), whereas nonhuman primate models sustain growth to neurulation and early organogenesis (up to E25), thereby bridging the gap between implantation and complex organ formation. In parallel, studies of rare early-stage primate embryos obtained from clinical procedures have yielded complementary insights into these developmental processes. In this review, we summarize recent progress in early primate embryo development research, emphasize the critical role of IVC systems in elucidating developmental processes, and discuss the integration of these experimental models with spatiotranscriptomic atlases to establish a more comprehensive framework for early human embryonic development.</p><p><strong>Key messages: </strong>Primate IVC systems offer accessible platforms for high-resolution dynamic observation and perturbation, while in vivo embryos provide physiologically faithful references. Coupling these complementary approaches reconstructs the trajectory of early human development, establishing a robust framework to decipher the causes of birth defects and facilitate mechanism-guided drug screening.</p>","PeriodicalId":9717,"journal":{"name":"Cells Tissues Organs","volume":" ","pages":"1-7"},"PeriodicalIF":1.9,"publicationDate":"2026-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146178119","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Inflammatory Response to Menstrual Fluid Does Not Induce Fibrotic Morphogenesis Program in Human Endometrial Stromal Cells.","authors":"Roman Eremichev, Mikhail Khandokhin, Natalya Alexandrushkina, Arina Radnaeva, Peter Nimiritsky, Vsevolod Tkachuk, Pavel Makarevich","doi":"10.1159/000550511","DOIUrl":"10.1159/000550511","url":null,"abstract":"<p><strong>Introduction: </strong>Human endometrium is one of peculiar tissues capable of scarless regeneration after injury during every menstrual cycle, birth, or surgery. However, it is disputable whether this feature should be attributed to specific regulatory factors of wound environment and menstrual fluid (MF) or to tissue-specific properties of endometrial mesenchymal stromal cells (eMSCs), which are pivotal participants of wound healing. We aimed to elucidate the role of eMSC tissue specificity in wound healing.</p><p><strong>Methods: </strong>We evaluated changes of eMSC transcriptomic profile in response to MF and their potency to granulation tissue formation in vitro in comparison with those of stromal cells from scar-forming organs - dermal and adipose MSC (dMSC and adMSC).</p><p><strong>Results: </strong>We have found that MF contains numerous inflammatory factors and induces a profound inflammatory response in both eMSC and dMSC, but a tissue-specific component was identified in their transcriptome profiles. Furthermore, transcriptomic tissue specificity was stable and present prior to MF treatment as well as after it, so we validated our findings against in vivo single-cell RNA-sequencing data from Human Protein Atlas. Tissue specificity traits were related to embryonic development and morphogenesis, suggesting a putative contribution of \"developmental imprinting\" in its establishment. Using in vitro models of fibroplasia, angiogenesis, and extracellular matrix deposition, we showed that eMSC lack the ability to induce these processes in contrast to dMSC and adMSC. Finally, we refined transcription factors (TFs) from stable tissue-specific genes that may explain the unique properties of eMSC and endometrium itself and can serve as potential targets to induce regeneration in scar-forming organs.</p><p><strong>Conclusion: </strong>eMSCs possess tissue-specific properties including stable expression of TFs that may explain the scarless regeneration of endometrium.</p>","PeriodicalId":9717,"journal":{"name":"Cells Tissues Organs","volume":" ","pages":"1-13"},"PeriodicalIF":1.9,"publicationDate":"2026-01-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146003092","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Media Comparisons for the Differentiation of Human Induced Pluripotent Stem Cells into the Otic Lineage.","authors":"Stefanie Klingenstein, Nils Hollweg, Stefan Liebau, Moritz Klingenstein","doi":"10.1159/000550296","DOIUrl":"10.1159/000550296","url":null,"abstract":"<p><strong>Introduction: </strong>Otic organoids differentiated from human pluripotent stem cells are three-dimensional in vitro cultures that broadly mimic the complexity and functionality of the human inner ear. They provide a valuable model for developmental and disease-related studies. However, current protocols differ substantially in efficiency and reproducibility. In this study, we investigated whether different stem cell maintenance media influence the differentiation of keratinocyte-derived induced pluripotent stem cells (kiPSCs) into the otic lineage.</p><p><strong>Methods: </strong>kiPSCs were cultured in either a self-made FTDA medium or the commercially available PeproGrow™ human embryonic stem cell medium and subsequently subjected to an established otic differentiation protocol. Early developmental stages, including the pre-placodal region, the otic placode, and pro-neural sensory regions, were analyzed using immunofluorescence and gene expression profiling.</p><p><strong>Results: </strong>While no significant differences were observed in iPSC maintenance or pluripotency between the two media, distinct differences emerged during otic differentiation. Media composition influenced the expression of placodal, otic, and pro-sensory markers at multiple stages, indicating differential responsiveness to otic induction cues.</p><p><strong>Conclusion: </strong>Our findings demonstrate that stem cell maintenance media composition is a critical determinant of subsequent otic lineage differentiation. These results provide guidance for optimizing stem cell culture conditions and improving the reproducibility of otic organoid differentiation protocols.</p>","PeriodicalId":9717,"journal":{"name":"Cells Tissues Organs","volume":" ","pages":"1-17"},"PeriodicalIF":1.9,"publicationDate":"2026-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145948294","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cytosolic Carboxypeptidase 1 Loss in Bone Marrow Mesenchymal Stem Cells Inhibited Osteogenic Differentiation by Enhancing Microtubule Glutamylation.","authors":"Cancan Pan, Xuyan Gong, Xuekui Wang, Huiyuan Wu, Yao Sun","doi":"10.1159/000546259","DOIUrl":"10.1159/000546259","url":null,"abstract":"<p><strong>Introduction: </strong>Cytosolic carboxypeptidase 1 (CCP1) is a deglutamylase that antagonizes polyglutamylation. Mutations in human CCP1 gene cause a severe disease known as childhood-onset neurodegeneration with cerebellar atrophy (CONDCA), which is characterized by marked growth retardation. However, the role and mechanisms of CCP1 in skeletal development remain unclear.</p><p><strong>Methods: </strong>In this study, we used CCP1 knockout (CCP1-KO) mice to assess bone mass changes by micro-CT, HE, alkaline phosphatase (ALP) staining, tartrate-resistant acid phosphatase staining and immunofluorescence staining. Changes in osteogenic differentiation, proliferation, and migration capacity of bone marrow mesenchymal stem cells (BMSCs) were assessed by ALP, alizarin red (ARS) staining, quantitative real-time PCR, EdU staining, and cell scratching assay. Then, tubulin glutamylation and primary cilia of BMSCs after deletion of CCP1 was analyzed by Western blot and immunofluorescence staining. Finally, CB839, an inhibitor of glutamine metabolism, was used to detect changes in the osteogenic differentiation ability and primary cilia of BMSCs after reducing the elevated glutamylation level.</p><p><strong>Results: </strong>CCP1-KO mice exhibited phenotypes relevant to humans, including reduced body size, decreased bone mass, and reduced bone density during growth and development. CCP1 deficiency impairs the proliferation, migration, and osteogenic differentiation of BMSCs. Meanwhile, the number of pre-osteoblasts derived from BMSCs is decreased, leading to impaired osteogenesis. At the cellular level, CCP1 loss results in aberrant tubulin glutamylation, increased microtubule glutamylation, and shortened primary cilia in BMSCs. Finally, reduction of abnormally elevated tubulin glutamylation was efficacious for promoting osteogenic differentiation of BMSCs and restoring primary cilia length of BMSCs.</p><p><strong>Conclusion: </strong>We propose that CCP1 plays a critical role in regulating BMSCs differentiation and promotes osteogenesis by modulating the post-translational modifications of tubulin, with a view to provide new targets for the prevention and treatment of hard tissue diseases.</p>","PeriodicalId":9717,"journal":{"name":"Cells Tissues Organs","volume":" ","pages":"137-152"},"PeriodicalIF":1.9,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143987015","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}