Journal of Cellular Physiology最新文献_第9页

Maintenance of Cardiac Microenvironmental Homeostasis: A Joint Battle of Multiple Cells 心脏微环境稳态的维持：多细胞的联合战斗。

IF 4.5 2区生物学

Journal of Cellular Physiology Pub Date : 2024-12-04 DOI: 10.1002/jcp.31496

Jiayu Yao, Youtao Zhang, Ziwen Wang, Yuejun Chen, Xingjuan Shi

引用次数: 0

METTL3-Dependent YTHDF2 Mediates TSC1 Expression to Regulate Alveolar Epithelial Mesenchymal Transition and Promote Idiopathic Pulmonary Fibrosis 依赖 METTL3 的 YTHDF2 介导 TSC1 的表达，从而调节肺泡上皮间充质转化并促进特发性肺纤维化。

IF 4.5 2区生物学

Journal of Cellular Physiology Pub Date : 2024-11-28 DOI: 10.1002/jcp.31473

Min Liu, Yingying Sheng, Mengyu Li, Tianyu Pan, Wei Jiang, Yafei Zhang, Xin Pan, Cheng Huang, Jun Li, Yuanyuan Wang

{"title":"METTL3-Dependent YTHDF2 Mediates TSC1 Expression to Regulate Alveolar Epithelial Mesenchymal Transition and Promote Idiopathic Pulmonary Fibrosis","authors":"Min Liu, Yingying Sheng, Mengyu Li, Tianyu Pan, Wei Jiang, Yafei Zhang, Xin Pan, Cheng Huang, Jun Li, Yuanyuan Wang","doi":"10.1002/jcp.31473","DOIUrl":"10.1002/jcp.31473","url":null,"abstract":"<div>\u0000 \u0000 <p>Diffuse, progressive interstitial lung disease with few treatment options and low survival rates is known as idiopathic pulmonary fibrosis (IPF). Alveolar epithelial cell damage and dysfunction are the main features of IPF. TSC1 has been documented to exert a pivotal function in governing cellular growth, proliferation, and ontogenesis. This work investigated TSC1's function and mechanism in IPF. Mice were given BLM to cause pulmonary fibrosis, and A549 cells underwent epithelial mesenchymal transition (EMT) in response to TGF-β1. According to the data, TSC1 expression was reduced in IPF. Overexpression of TSC1 was established by adenopathy-associated virus in vivo and adenovirus in vitro to significantly block the EMT process. Besides, the findings from the RNA-sequencing analysis indicate that overexpression of TSC1 mitigated the EMT process by suppressing the activation of the AKT/mTOR pathway via downregulation of ACTN4 expression. To examine the upstream regulatory mechanism, we employed the SRAMP database to predict m<sup>6</sup>A modification of TSC1 mRNA, followed by verification of m<sup>6</sup>A modification levels and expression using MERIP-qPCR, Dot blot, RT-qPCR, and WB. The results indicated a high degree of m<sup>6</sup>A modification in TSC1 mRNA in pulmonary fibrosis. The expression of METTL3 was further found to be significantly elevated. METTL3 knockdown impeded EMT progression. METTL3 inhibits TSC1 expression by increasing TSC1 m<sup>6</sup>A modification through the reading protein YTHDF2. In conclusion, our study elucidated that the METTL3/YTHDF2/TSC1 signaling axis activates the AKT/mTOR pathway to promote the development of IPF. This study provides potential molecular-level therapeutic targets for IPF disease.</p></div>","PeriodicalId":15220,"journal":{"name":"Journal of Cellular Physiology","volume":"240 1","pages":""},"PeriodicalIF":4.5,"publicationDate":"2024-11-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142739532","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Osteoclast Secretes Stage-Specific Key Molecules for Modulating Osteoclast–Osteoblast Communication 破骨细胞分泌特定阶段的关键分子，调节破骨细胞与成骨细胞之间的交流

IF 4.5 2区生物学

Journal of Cellular Physiology Pub Date : 2024-11-28 DOI: 10.1002/jcp.31484

Yi-fei Fu, Shu-wen Shi, Jun-jie Wu, Zheng-dong Yuan, Lei-sheng Wang, Hao Nie, Zheng-yu Zhang, Xian Wu, Yue-chun Chen, Hui-bo Ti, Ke-yue Zhang, Dong Mao, Jun-xing Ye, Xia Li, Feng-lai Yuan

{"title":"Osteoclast Secretes Stage-Specific Key Molecules for Modulating Osteoclast–Osteoblast Communication","authors":"Yi-fei Fu, Shu-wen Shi, Jun-jie Wu, Zheng-dong Yuan, Lei-sheng Wang, Hao Nie, Zheng-yu Zhang, Xian Wu, Yue-chun Chen, Hui-bo Ti, Ke-yue Zhang, Dong Mao, Jun-xing Ye, Xia Li, Feng-lai Yuan","doi":"10.1002/jcp.31484","DOIUrl":"10.1002/jcp.31484","url":null,"abstract":"<div>\u0000 \u0000 <p>In most cases of bone metabolic disorders, such as osteoporosis and osteomalacia, these conditions are often attributed to dysfunctional osteoclasts, leading to their common characterization as “destructors.” In addition to the widely documented regulatory process where osteoblasts direct osteoclastic bone resorption, there is increasing evidence suggesting that osteoclasts also in turn influence osteoblastic bone formation through direct and indirect mechanisms. It is well-known that differentiation of osteoclasts involves several stages, each characterized by specific cellular features and functions. Stage-specific key molecules secreted during these stages play a critical role in mediating osteoclast–osteoblast communication. In this review, we described the different stages of osteoclast differentiation and reviewed stage-specific key molecules involved in osteoclasts-osteoblasts communication. We highlighted that a detailed understanding of these processes and molecular mechanism could facilitate the development of novel treatments for bone metabolic disorders.</p></div>","PeriodicalId":15220,"journal":{"name":"Journal of Cellular Physiology","volume":"240 1","pages":""},"PeriodicalIF":4.5,"publicationDate":"2024-11-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142739535","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Spontaneously Immortalised Nonhuman Primate Müller Glia Cell Lines as Source to Explore Retinal Reprogramming Mechanisms for Cell Therapies 自发永生化的非人灵长类 Müller 神经胶质细胞系是探索细胞疗法视网膜重编程机制的来源。

IF 4.5 2区生物学

Journal of Cellular Physiology Pub Date : 2024-11-28 DOI: 10.1002/jcp.31482

Ahmed Salman, Arantxa Bolinches-Amorós, Tina Storm, Daniela Moralli, Paulina Bryika, Angela J. Russell, Stephen G. Davies, Alun R. Barnard, Robert E. MacLaren

{"title":"Spontaneously Immortalised Nonhuman Primate Müller Glia Cell Lines as Source to Explore Retinal Reprogramming Mechanisms for Cell Therapies","authors":"Ahmed Salman, Arantxa Bolinches-Amorós, Tina Storm, Daniela Moralli, Paulina Bryika, Angela J. Russell, Stephen G. Davies, Alun R. Barnard, Robert E. MacLaren","doi":"10.1002/jcp.31482","DOIUrl":"10.1002/jcp.31482","url":null,"abstract":"<p>Cell replacement therapies for ocular diseases characterised by photoreceptors degeneration are challenging due to poor primary cell survival in culture. A stable retinal cell source to replace lost photoreceptors holds promise. Müller glia cells play a pivotal role in retinal homoeostasis by providing metabolic and structural support to retinal neurons, preventing aberrant photoreceptors migration, and facilitating safe glutamate uptake. In fish and amphibians, injured retinas regenerate due to Müller-like glial stem cells, a phenomenon absent in the mammalian retina for unknown reasons. Research on Müller cells has been complex due to difficulties in obtaining pure cell population and their rapid de-differentiation in culture. While various Müller glia cell lines from human and rats are described, no nonhuman primate Müller glia cell line is currently available. Here, we report spontaneously immortalised Müller glia cell lines derived from macaque neural retinas that respond to growth factors and expand indefinitely in culture. They exhibit Müller cells morphology, such as an elongated shape and cytoplasmic projections, express Müller glia markers (VIMENTIN, GLUTAMINE SYNTHASE, glutamate-aspartate transporter, and CD44), and express stem cell markers such as PAX6 and SOX2. In the presence of factors that induce photoreceptor differentiation, these cells show a shift in gene expression patterns suggesting a state of de-differentiation, a phenomenon known in reprogrammed mammalian Müller cells. The concept of self-renewing retina might seem unfeasible, but not unprecedented. While vertebrate Müller glia have a regeneration potential absent in mammals, understanding the mechanisms behind reprogramming of Müller glia in mammals could unlock their potential for treating retinal degenerative diseases.</p>","PeriodicalId":15220,"journal":{"name":"Journal of Cellular Physiology","volume":"240 1","pages":""},"PeriodicalIF":4.5,"publicationDate":"2024-11-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11774137/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142739550","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

CCL2-CCR2 Axis Inhibition in Osteosarcoma Cell Model: The Impact of Oxygen Level on Cell Phenotype 骨肉瘤细胞模型中的 CCL2-CCR2 轴抑制：氧含量对细胞表型的影响

IF 4.5 2区生物学

Journal of Cellular Physiology Pub Date : 2024-11-25 DOI: 10.1002/jcp.31489

Agne Petrosiute, Justina Musvicaitė, Donatas Petroška, Alvilė Ščerbavičienė, Sascha Arnold, Jurgita Matulienė, Aurelija Žvirblienė, Daumantas Matulis, Asta Lučiūnaitė

{"title":"CCL2-CCR2 Axis Inhibition in Osteosarcoma Cell Model: The Impact of Oxygen Level on Cell Phenotype","authors":"Agne Petrosiute, Justina Musvicaitė, Donatas Petroška, Alvilė Ščerbavičienė, Sascha Arnold, Jurgita Matulienė, Aurelija Žvirblienė, Daumantas Matulis, Asta Lučiūnaitė","doi":"10.1002/jcp.31489","DOIUrl":"10.1002/jcp.31489","url":null,"abstract":"<p>Treatment of osteosarcoma is hampered by tumor hypoxia and requires alternative approaches. Although the CCL2-CCR2 axis is indispensable in tumor-induced inflammation and angiogenesis, its blockade has not been effective to date. This study aimed to characterize how CCR2 inhibition affects the crosstalk of osteosarcoma cells with immune cells to better delineate tumor resistance mechanisms that help withstand such treatment. In this study, 143B cells were exposed to healthy donor PBMC supernatants in a transwell assay lacking direct cell-to-cell contact and subjected to different oxygen concentrations. In addition, mice bearing orthotopic 143B tumors were subjected to CCR2 antagonist treatment. Our findings show that hypoxic conditions alter cytokine and cancer- related protein expression on cells and impair CCR2 antagonist effects in the experimental osteosarcoma model. CCL2-CCR2 axis blockade in the 143B xenografts, which are positive for hypoxia marker CAIX, did not slow 143B tumor growth or metastasis but altered tumor microenvironment by VEGFR downregulation and shift in the CD44-positive cell population towards high CD44 expression. This study highlights differential responses of tumor cells to CCR2 antagonists in the presence of different oxygen saturations and expands our knowledge of compensatory mechanisms leading to CCL2-CCR2 treatment resistance.</p>","PeriodicalId":15220,"journal":{"name":"Journal of Cellular Physiology","volume":"240 1","pages":""},"PeriodicalIF":4.5,"publicationDate":"2024-11-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11747949/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142716296","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Signaling Regulation of FAM134-Dependent ER-Phagy in Cells 细胞中 FAM134 依赖性 ER 吞噬的信号调控

IF 4.5 2区生物学

Journal of Cellular Physiology Pub Date : 2024-11-25 DOI: 10.1002/jcp.31492

Alessandro Palma, Alessio Reggio

引用次数: 0

FMNL3 Promotes Migration and Invasion of Breast Cancer Cells via Inhibiting Rad23B-Induced Ubiquitination of Twist1 FMNL3通过抑制Rad23B诱导的Twist1泛素化促进乳腺癌细胞的迁移和侵袭

IF 4.5 2区生物学

Journal of Cellular Physiology Pub Date : 2024-11-25 DOI: 10.1002/jcp.31481

Binggong Zhao, Dong-Man Ye, Shujing Li, Yong Zhang, Yang Zheng, Jie Kang, Luhong Wang, Nannan Zhao, Bashir Ahmad, Jing Sun, Tao Yu, Huijian Wu

{"title":"FMNL3 Promotes Migration and Invasion of Breast Cancer Cells via Inhibiting Rad23B-Induced Ubiquitination of Twist1","authors":"Binggong Zhao, Dong-Man Ye, Shujing Li, Yong Zhang, Yang Zheng, Jie Kang, Luhong Wang, Nannan Zhao, Bashir Ahmad, Jing Sun, Tao Yu, Huijian Wu","doi":"10.1002/jcp.31481","DOIUrl":"10.1002/jcp.31481","url":null,"abstract":"<div>\u0000 \u0000 <p>Breast cancer is a heterogeneous malignant tumor, and its high metastasis rate depends on the abnormal activation of cell dynamics. Formin-like protein 3 (FMNL3) plays an important role in the formation of various cytoskeletons that participate in cell movement. The objective of this study was to explore the function of FMNL3 in breast cancer progression and endeavor to reveal the molecular mechanism of this phenomenon. We found that FMNL3 was abnormally highly expressed in aggressive breast cancer cells and tissues, and it significantly inhibited E-cadherin expression. FMNL3 could specifically interact with Twist1 rather than other epithelial–mesenchymal transition transcription factors (EMT-TFs). We also found that FMNL3 enhanced the repressive effect of Twist1 on <i>CDH1</i> transcription in breast cancer cells. Further mechanism studies showed that FMNL3 suppressed the ubiquitin degradation of Twist1 by inhibiting the interaction between Twist1 and Rad23B, the ubiquitin transfer protein of Twist1. In vitro functional experiments, it was confirmed that FMNL3 promoted the migration and invasion of breast cancer cells by regulating Twist1. Furthermore, Twist1 could directly bind to the <i>fmnl3</i> promoter to facilitate FMNL3 transcription. To conclude, this study indicated that FMNL3 acted as a pro-metastasis factor in breast cancer by promoting Twist1 stability to suppress <i>CDH1</i> transcription.</p></div>","PeriodicalId":15220,"journal":{"name":"Journal of Cellular Physiology","volume":"240 1","pages":""},"PeriodicalIF":4.5,"publicationDate":"2024-11-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142709643","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Single-Cell RNA-Seq and Histological Analysis Reveals Dynamic Lrig1 Expression During Salivary Gland Development 单细胞 RNA-Seq 和组织学分析揭示唾液腺发育过程中 Lrig1 的动态表达

IF 4.5 2区生物学

Journal of Cellular Physiology Pub Date : 2024-11-25 DOI: 10.1002/jcp.31487

Shumin Liu, Yuanyuan Li, Delan Huang, Ming Liu, Xinye Zhang, Hui Zhao, Huan Liu, Qiuhui Li, Zhi Chen

{"title":"Single-Cell RNA-Seq and Histological Analysis Reveals Dynamic Lrig1 Expression During Salivary Gland Development","authors":"Shumin Liu, Yuanyuan Li, Delan Huang, Ming Liu, Xinye Zhang, Hui Zhao, Huan Liu, Qiuhui Li, Zhi Chen","doi":"10.1002/jcp.31487","DOIUrl":"10.1002/jcp.31487","url":null,"abstract":"<div>\u0000 \u0000 <p>The development of the salivary gland (SG) is a complex process regulated by multiple signaling pathways in a spatiotemporal manner. Various stem/progenitor cell populations and respective cell lineages are involved in SG morphogenesis and postnatal maturation. Leucine-rich repeats and immunoglobulin-like domains 1 (LRIG1) has been identified as critical regulator of stem cells by virtue of its ability to restrain stem cell proliferation, indicating its potential role in the development of several maxillofacial tissues and in the regulation of the quiescence in adult tissues. This study aimed to investigate the expression pattern and functions of Lrig1 in the developing and mature murine submandibular gland (SMG). To accomplish this objective, we collected the murine SMGs at different developmental stages and examined the expression pattern and levels of Lrig1 with qRT-PCR, immunofluorescent (IF) and RNAscope staining. We observed that Lrig1 was widely distributed in both epithelial and mesenchymal cells throughout embryonic and neonatal stages, with specific localization in the more mature epithelium. Furthermore, through single-cell RNA sequencing (scRNA-Seq) and IF techniques, we confirmed that LRIG1 is highly concentrated along with SMG progenitor markers in acinar and basal cells. Additionally, transcription factors (TFs) that could regulate LRIG1 expression were predicted from JASPAR databases and their motifs were identified by the UCSC browser's BLAT tool. Gene Ontology (GO) enrichment analyses on postnatal day 5 (PN5) scRNA-Seq data also provided insights into Lrig1's functions in SG development. Finally, we also conducted in vitro experiments on a human salivary gland (HSG) cell line to assess LRIG1's impact on HSG proliferation and migration, as well as its potential upstream regulatory TFs. Taken together, our study reveals that LRIG1 plays a vital role in SG development.</p></div>","PeriodicalId":15220,"journal":{"name":"Journal of Cellular Physiology","volume":"240 1","pages":""},"PeriodicalIF":4.5,"publicationDate":"2024-11-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142716298","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Phenomics Demonstrates Cytokines Additive Induction of Epithelial to Mesenchymal Transition 表型组学证明细胞因子可诱导上皮细胞向间质转化

IF 4.5 2区生物学

Journal of Cellular Physiology Pub Date : 2024-11-20 DOI: 10.1002/jcp.31491

Alphonse Boché, Alexandra Landras, Mathieu Morel, Sabrina Kellouche, Franck Carreiras, Ambroise Lambert

{"title":"Phenomics Demonstrates Cytokines Additive Induction of Epithelial to Mesenchymal Transition","authors":"Alphonse Boché, Alexandra Landras, Mathieu Morel, Sabrina Kellouche, Franck Carreiras, Ambroise Lambert","doi":"10.1002/jcp.31491","DOIUrl":"10.1002/jcp.31491","url":null,"abstract":"<p>Epithelial to mesenchymal transition (EMT) is highly plastic with a programme where cells lose adhesion and become more motile. EMT heterogeneity is one of the factors for disease progression and chemoresistance in cancer. Omics characterisations are costly and challenging to use. We developed single cell phenomics with easy to use wide-field fluorescence microscopy. We analyse over 70,000 cells and combined 53 features. Our simplistic pipeline allows efficient tracking of EMT plasticity, with a single statistical metric. We discriminate four high EMT plasticity cancer cell lines along the EMT spectrum. We test two cytokines, inducing EMT in all cell lines, alone or in combination. The single cell EMT metrics demonstrate the additive effect of cytokines combination on EMT independently of cell line EMT spectrum. The effects of cytokines are also observed at the front of migration during wound healing assay. Single cell phenomics is uniquely suited to characterise the cellular heterogeneity in response to complex microenvironment and show potential for drug testing assays.</p>","PeriodicalId":15220,"journal":{"name":"Journal of Cellular Physiology","volume":"240 1","pages":""},"PeriodicalIF":4.5,"publicationDate":"2024-11-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11747948/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142675848","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Serinc5 Regulates Sequential Chondrocyte Differentiation by Inhibiting Sox9 Function in Pre-Hypertrophic Chondrocytes Serinc5 通过抑制肥大前期软骨细胞中 Sox9 的功能来调控软骨细胞的顺序分化

IF 4.5 2区生物学

Journal of Cellular Physiology Pub Date : 2024-11-20 DOI: 10.1002/jcp.31490

Kenji Hata, Kanta Wakamori, Akane Hirakawa-Yamamura, Sachi Ichiyama-Kobayashi, Masaya Yamaguchi, Daisuke Okuzaki, Yoshifumi Takahata, Tomohiko Murakami, Narikazu Uzawa, Takashi Yamashiro, Riko Nishimura

{"title":"Serinc5 Regulates Sequential Chondrocyte Differentiation by Inhibiting Sox9 Function in Pre-Hypertrophic Chondrocytes","authors":"Kenji Hata, Kanta Wakamori, Akane Hirakawa-Yamamura, Sachi Ichiyama-Kobayashi, Masaya Yamaguchi, Daisuke Okuzaki, Yoshifumi Takahata, Tomohiko Murakami, Narikazu Uzawa, Takashi Yamashiro, Riko Nishimura","doi":"10.1002/jcp.31490","DOIUrl":"10.1002/jcp.31490","url":null,"abstract":"<p>The growth plate is the primary site of longitudinal bone growth with chondrocytes playing a pivotal role in endochondral bone development. Chondrocytes undergo a series of differentiation steps, resulting in the formation of a unique hierarchical columnar structure comprising round, proliferating, pre-hypertrophic, and hypertrophic chondrocytes. Pre-hypertrophic chondrocytes, which exist in the transitional stage between proliferating and hypertrophic stages, are a critical cell population in the growth plate. However, the molecular basis of pre-hypertrophic chondrocytes remains largely undefined. Here, we employed scRNA-seq analysis on fluorescently labeled growth plate chondrocytes for their molecular characterization. Serine incorporator 5 (<i>Serinc5</i>) was identified as a marker gene for pre-hypertrophic chondrocytes. Histological analysis revealed that Serinc5 is specifically expressed in pre-hypertrophic chondrocytes, overlapping with Indian hedgehog (Ihh). Serinc5 represses cell proliferation and <i>Col2a1</i> and <i>Acan</i> expression by inhibiting the transcriptional activity of Sox9 in primary chondrocytes. Chromatin profiling using ChIP-seq and ATAC-seq revealed an active enhancer of <i>Serinc5</i> located in intron 1, with its chromatin status progressively activated during chondrocyte differentiation. Collectively, our findings suggest that Serinc5 regulates sequential chondrocyte differentiation from proliferation to hypertrophy by inhibiting Sox9 function in pre-hypertrophic chondrocytes, providing novel insights into the mechanisms underlying chondrocyte differentiation in growth plates.</p>","PeriodicalId":15220,"journal":{"name":"Journal of Cellular Physiology","volume":"240 1","pages":""},"PeriodicalIF":4.5,"publicationDate":"2024-11-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11747958/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142681883","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0