更新于：2024-05-01

SOX5

SRY-box transcription factor 5

更新于：2024-05-01

基本信息

别名

L-SOX5、MGC35153、SOX5

+ [2]

简介

Transcription factor involved in chondrocytes differentiation and cartilage formation. Specifically binds the 5'-AACAAT-3' DNA motif present in enhancers and super-enhancers and promotes expression of genes important for chondrogenesis, including cartilage matrix protein-coding genes, such as COL2A1 and AGC1. Required for overt chondrogenesis when condensed prechondrocytes differentiate into early stage chondrocytes: SOX5 and SOX6 cooperatively bind with SOX9 on active enhancers and super-enhancers associated with cartilage-specific genes, and thereby potentiate SOX9's ability to transactivate. Not involved in precartilaginous condensation, the first step in chondrogenesis, during which skeletal progenitors differentiate into prechondrocytes. Together with SOX6, required to form and maintain a pool of highly proliferating chondroblasts between epiphyses and metaphyses, to form columnar chondroblasts, delay chondrocyte prehypertrophy but promote hypertrophy, and to delay terminal differentiation of chondrocytes on contact with ossification fronts. Binds to the proximal promoter region of the myelin protein MPZ gene.

关联

100 项与 SOX5 相关的临床结果

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100 项与 SOX5 相关的转化医学

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0 项与 SOX5 相关的专利（医药）

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515

项与 SOX5 相关的文献（医药）

2024-02-10·Journal of applied genetics

The role of multidisciplinary diagnostic and therapeutic model of care in Lamb-Shaffer syndrome - case report.

Article

作者: Urszula Sajewicz-Radtke ; Ariadna Łada-Maśko ; Małgorzata Lipowska ; Bartosz M Radtke ; Beata S Lipska-Ziętkiewicz ; Katarzyna Krempla-Patron

This case study illustrates a multidisciplinary diagnostic and therapeutic model of care for a 7-year-old male with Lamb-Shaffer syndrome (LAMSHF). LAMSHF is an ultra-rare genetic neurodevelopmental disorder, caused by heterozygous alterations in the SOX5 gene. An integrative model of therapy of cognitive functions and speech is described. The presented approach allows the development of language competences through stimulation of basic cognitive functions, which allows the learning of the abstract rules of an inflected language. A surprising, unexpected improvement in the cognitive functioning of the child was observed (both in terms of reasoning and speech), as well as an increase in his independence. The clinically important problem of the need for continued stimulation of cognitive development, in spite of the unfavourable prognosis associated with LAMSHF, is highlighted.

2024-02-01·Journal of the National Comprehensive Cancer Network : JNCCN

An Infant-Type Hemispheric Glioma With SOX5::ALK: A Novel Fusion.

Article

作者: Chia Chin Tsai ; Man-Hsu Huang ; Chia-Lang Fang ; Kevin Li-Chun Hsieh ; Tsung-Han Hsieh ; Wan-Ling Ho ; Hsi Chang ; Min-Lan Tsai ; Yu-Chien Kao ; James S Miser ; Tai-Tong Wong ; Min-Yu Su ; Yen-Lin Liu

Infant-type hemispheric glioma (IHG) is a rare pediatric brain tumor with variable response to chemotherapy and radiotherapy. Molecular insights into IHG can be useful in identifying potentially active targeted therapy. A male fetus was found to have congenital hydrocephalus at the gestational age of 37 weeks. Fetal MRI showed a 2.6 × 2.0-cm tumor located at the frontal horn of the left lateral ventricle, involving the left basal nuclei and thalamus. Tumor biopsy at the age of 2 days revealed an IHG consisting of spindle tumor cells with strong expression of GFAP and ALK. Targeted RNA sequencing detected a novel fusion gene of SOX5::ALK. After initial chemotherapy with cyclophosphamide, carboplatin, and etoposide for 2 cycles, the tumor size progressed markedly and the patient underwent a subtotal resection of brain tumor followed by treatment with lorlatinib, an ALK tyrosine kinase inhibitor with central nervous system (CNS) activity. After 3 months of treatment, reduction of tumor size was observed. After 14 months of treatment, partial response was achieved, and the infant had normal growth and development. In conclusion, we identified a case of congenital IHG with a novel SOX5::ALK fusion that had progressed after chemotherapy and showed partial response and clinical benefit after treatment with the CNS-active ALK inhibitor lorlatinib.

2024-01-29·BMC genomics

Single-cell RNA-seq mapping of chicken peripheral blood leukocytes.

Article

作者: Matilda Maxwell ; Robert Söderlund ; Sonja Härtle ; Eva Wattrang

BACKGROUND:

Single-cell transcriptomics provides means to study cell populations at the level of individual cells. In leukocyte biology this approach could potentially aid the identification of subpopulations and functions without the need to develop species-specific reagents. The present study aimed to evaluate single-cell RNA-seq as a tool for identification of chicken peripheral blood leukocytes. For this purpose, purified and thrombocyte depleted leukocytes from 4 clinically healthy hens were subjected to single-cell 3' RNA-seq. Bioinformatic analysis of data comprised unsupervised clustering of the cells, and annotation of clusters based on expression profiles. Immunofluorescence phenotyping of the cell preparations used was also performed.

RESULTS:

Computational analysis identified 31 initial cell clusters and based on expression of defined marker genes 28 cluster were identified as comprising mainly B-cells, T-cells, monocytes, thrombocytes and red blood cells. Of the remaining clusters, two were putatively identified as basophils and eosinophils, and one as proliferating cells of mixed origin. In depth analysis on gene expression profiles within and between the initial cell clusters allowed further identification of cell identity and possible functions for some of them. For example, analysis of the group of monocyte clusters revealed subclusters comprising heterophils, as well as putative monocyte subtypes. Also, novel aspects of TCRγ/δ + T-cell subpopulations could be inferred such as evidence of at least two subtypes based on e.g., different expression of transcription factors MAF, SOX13 and GATA3. Moreover, a novel subpopulation of chicken peripheral B-cells with high SOX5 expression was identified. An overall good correlation between mRNA and cell surface phenotypic cell identification was shown.

CONCLUSIONS:

Taken together, we were able to identify and infer functional aspects of both previously well known as well as novel chicken leukocyte populations although some cell types. e.g., T-cell subtypes, proved more challenging to decipher. Although this methodology to some extent is limited by incomplete annotation of the chicken genome, it definitively has benefits in chicken immunology by expanding the options to distinguish identity and functions of immune cells also without access to species specific reagents.

项与 SOX5 相关的新闻（医药）

2024-04-03

·今日头条

发挥致癌作用！吉林大学发文揭示黑色素瘤最新进展机制和潜在预后标志物

本文为转化医学网原创，转载请注明出处作者：Rainbow 导读：越来越多证据表明，lncRNA可以作为癌基因或肿瘤抑制基因发挥作用，通过转录和转录后调控机制参与肿瘤细胞的增殖、迁移、侵袭和凋亡。 4月1日，吉林大学研究团队在期刊《Cell Death Discovery》上在线发表题为“A novel long non-coding RNA SLNCR1 promotes proliferation, migration, and invasion of melanoma via transcriptionally regulating SOX5”的研究论文，研究表明SLNCR1通过靶向SOX5促进黑色素瘤的EMT，这些发现表明SLNCR1可能作为评估黑色素瘤发病率和预后的潜在标志物。 https://www-nature-com.libproxy1.nus.edu.sg/articles/s41420-024-01922-7 研究背景 01 黑色素细胞起源于神经嵴，在胚胎发育期间迁移至身体的各个部位，如皮肤、葡萄膜、脑膜和粘膜等。它们的恶性转化导致黑色素瘤。与黑色素瘤相关的危险因素包括日晒、黑色素细胞痣的数量和大小，以及家族病史。黑色素瘤是最致命的皮肤癌，早期发现是成功治疗的关键。大约75%的黑色素瘤具有高度转移性，近年来发病率逐年增加。因此，开发黑色素瘤的早期诊断和预后标志物对于改善人类健康至关重要。长链非编码RNA（lncRNA）是一类长度超过200nts的非蛋白编码转录本。越来越多证据表明，lncRNA可以作为癌基因或肿瘤抑制基因发挥作用，通过转录和转录后调控机制参与肿瘤细胞的增殖、迁移、侵袭和凋亡。类固醇受体RNA激活因子（SRA）样非编码RNA（SLNCR1）是一种最近发现的长链非编码RNA，位于人类染色体17q24.3上。尽管SLNCR1是一个相对新颖的lncRNA，但几项研究表明，在各种癌症中SLNCR1的表达上调，例如非小细胞肺癌、乳腺癌、宫颈癌和甲状腺状癌，并可能促进肿瘤进展。最近一项研究发现，SLNCR1参与调节黑色素瘤的侵袭，但其在黑色素瘤中的具体功能和潜在机制尚不清楚，值得进一步研究。研究发现 02 研究人员通过TCGA数据库和Kaplan-Meier方法的黑色素瘤组织样本进行了综合分析，以研究SLNCR1表达在黑色素瘤患者中的预后价值。随后，研究人员进行了qRT-PCR和荧光原位杂交（FISH）测定，分别鉴定了SLNCR1在组织和细胞中的表达水平和定位。利用shRNAs载体的功能丧失测定用于研究SLNCR1的潜在影响。数据显示，SLNCR1在人类恶性黑色素瘤组织和细胞系中显著上调，并且作为致癌基因发挥作用。沉默SLNCR1抑制了黑色素瘤细胞的增殖、迁移、侵袭，并且在小鼠异种移植模型中抑制了肿瘤发生。此外，研究人员采用生物信息学预测分析，结合双荧光素酶报告基因分析和功能拯救实验，阐明了SLNCR1/SOX5轴在黑色素瘤中的机制靶点。研究人员发现，SLNCR1通过靶向SOX5促进了人类黑色素瘤的EMT，因为SLNCR1表达水平下调导致SOX5蛋白水平下降，从而抑制黑色素瘤肿瘤发生。研究为更精准地诊断和治疗人类黑色素瘤提供了有希望的见解。研究结论 03 综上所述，研究表明SLNCR1通过靶向SOX5促进黑色素瘤的EMT，这些发现表明SLNCR1可能作为评估黑色素瘤发病率和预后的潜在标志物。参考资料： https://www-nature-com.libproxy1.nus.edu.sg/articles/s41420-024-01922-7 注：本文旨在介绍医学研究进展，不能作为治疗方案参考。如需获得健康指导，请至正规医院就诊。热门·直播/活动 🕓 上海｜06月14日-16日 ▶ 第六届上海国际癌症大会将于6月14-16日在上海举办，学科交叉，共同推进肿瘤研究与诊治多模态！ 🕓 北京｜09月20日-21日 ▶ 第五届单细胞技术应用研讨会暨空间组学前沿研讨会欢迎您的参与！点击对应文字查看详情

2023-10-14

·生物谷

研究揭示人类基因组中的“年轻化”基因

随着人口老龄化的到来，衰老相关疾病的高发正成为健康挑战。延缓衰老以及增强衰老组织活力和功能维持，进而促进老年健康是亟待解决的科学难题。细胞衰老（cellular senescence）是器官衰老乃至机随着人口老龄化的到来，衰老相关疾病的高发正成为健康挑战。延缓衰老以及增强衰老组织活力和功能维持，进而促进老年健康是亟待解决的科学难题。细胞衰老（cellular senescence）是器官衰老乃至机体功能退行的本质特征和内在驱动力，为老年慢病提供了机制框架和干预思路。如何延缓甚至逆转细胞衰老，已成为生命科学领域最前沿的科学问题之一。细胞更生（cellular rejuvenation）是指通过干预手段实现衰老细胞年轻化、重现细胞活力的过程。通过重塑表观遗传和基因表达程序使细胞“返老还童”，是延缓衰老、防治衰老相关疾病的重要方法和策略之一，这使得该领域迅速成为科学家关注的焦点。中国科学院动物研究所研究员刘光慧及合作者，在国际上率先利用体细胞重编程（somatic reprogramming）技术，在衰老程度高、速度快的人类儿童早衰症（Hutchinson Gilford progeria syndrome，HGPS）成纤维细胞中导入四个Yamanaka重编程因子OSKM（Oct4、Sox2、Klf4、c-Myc），实现了衰老细胞表观基因组重塑，逆转了人类细胞的衰老时钟。该研究衍生了后续一系列通过部分重编程（partial reprogramming）技术进行衰老干预的探索，并在啮齿类动物模型中取得了重要进展。目前，部分重编程技术已成为实现器官和细胞更生的重要路径。病毒载体介导的重编程因子“疗法”在模式动物中显示出延缓器官退变的潜力。然而，基于重编程因子的细胞更生方案不可避免地存在擦除成体细胞分化状态、改变初始“细胞身份”（cell identity）、诱发肿瘤等风险。这在一定程度上限制了重编程技术在衰老干预中的临床应用前景。因此，领域内亟需发现独立于重编程因子的全新细胞更生因子，并据此发展更为安全、高效的衰老干预策略。 10月12日，动物所刘光慧研究组、曲静研究组，联合中国科学院北京基因组研究所张维绮课题组、任捷课题组，在《细胞-干细胞》（Cell Stem Cell）上，在线发表了题为Genome-wide CRISPR activation screening in senescent cells reveals SOX5 as a driver and therapeutic target of rejuvenation的研究论文。该研究首次通过基于人间充质前体细胞（human mesenchymal precursor cell，hMPC）的全基因组基因增强（Gain-of-function）筛选，鉴定出一系列促更生因子（rejuvenation factor）。其中，转录因子SOX5为筛选名单中全新、强效的更生因子，可通过靶向激活HMGB2的表达来重塑衰老细胞、重启细胞活力。更重要的是，基于SOX5过表达的“基因疗法”可以延缓小鼠关节衰老，促进关节软骨再生并改善骨关节炎症状。这为人类衰老相关疾病的防治提供了新的研究方向。科研人员基于该团队前期建立的人间充质前体细胞衰老研究体系，利用CRISPR激活（CRISPR activation，CRISPRa）工具介导的基因功能增强筛选技术，对全基因组范围内的两万多个蛋白编码基因进行全面排查，首次系统鉴定人间充质前体细胞的更生因子合集。通过对排名前列的强效更生因子开展独立功能分析，研究证实了这些因子的激活均可延缓人间充质前体细胞衰老，提示这个更生因子合集是一个值得挖掘的基因资源库。其中，转录因子SOX5与Yamanaka重编程因子SOX2属同一蛋白家族，且表现出显著的促细胞年轻化能力，因而成为研究关注的焦点。进一步，该研究通过多种技术手段、结合多种生理与病理性人类细胞衰老模型，证实SOX5可在不改变细胞身份的前提下促进人类细胞更生。为探讨更生背后的分子机制，研究通过表观和转录组学技术联合分析SOX5的作用靶点，发现了SOX5可作为转录激活因子结合于衰老抑制基因HMGB2增强子区域，从而激活HMGB2的表达，启动细胞年轻化进程。与之相对，抑制SOX5或HMGB2表达会加速细胞衰老。由此，该团队揭示了SOX5-HMGB2轴或可作为干预人类细胞衰老的关键靶标。研究通过在老年小鼠关节给予SOX5基因治疗验证其潜在应用价值。结果显示，SOX5基因治疗可有效延缓关节细胞衰老，抑制骨赘和滑膜增生，降低关节腔炎症水平并促进软骨再生。行为学实验进一步支持了上述成果即治疗组动物的肢体抓力显著提升。进而，该研究平行比较了SOX5基因治疗和Yamanaka四因子OSKM基因治疗在延缓骨关节炎方面的效果。两种处理在多项关节衰老的评价指标上效果相当，但由于SOX5单因子治疗不会引起细胞身份的改变，且SOX5单因子核酸编码序列较短，更易在细胞中均衡表达，因而在长期干预效果上可能具有更好的安全性和有效性。综上，基于SOX5的基因疗法或有望实现器官衰老的干预，助力延长健康寿命。该成果是合作团队于2021年明确人类全基因组衰老促进基因名录（Science Translational Medicine 2021）后，针对人类基因组中衰老抑制基因，首次系统筛选出SOX5等新型促更生因子。该研究加深了科学界对衰老程序化理论的认识，揭示了独立于重编程因子的全新细胞更生因子合集，并发展了逆转细胞和组织衰老的新型策略。这些新的知识和技术体系为阐明驱动衰老的分子通路、建立人类器官衰老及相关退行性疾病的临床诊断及干预手段提供了新可能。该研究由动物所、北京基因组所、北京干细胞与再生医学研究院、首都医科大学宣武医院等合作完成。研究工作得到科学技术部、国家自然科学基金委员会、中国科学院和北京市等的支持。研究揭示人类基因组中的“年轻化”基因