更新于：2024-05-01

TBX2

T-box transcription factor 2

更新于：2024-05-01

基本信息

别名

T-box protein 2、T-box transcription factor 2、T-box transcription factor TBX2

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简介

Transcription factor which acts as a transcriptional repressor (PubMed:11111039, PubMed:11062467, PubMed:12000749, PubMed:22844464, PubMed:30599067). May also function as a transcriptional activator (By similarity). Binds to the palindromic T site 5'-TTCACACCTAGGTGTGAA-3' DNA sequence, or a half-site, which are present in the regulatory region of several genes (PubMed:11111039, PubMed:12000749, PubMed:22844464, PubMed:30599067). Required for cardiac atrioventricular canal formation (PubMed:29726930). May cooperate with NKX2.5 to negatively modulate expression of NPPA/ANF in the atrioventricular canal (By similarity). May play a role as a positive regulator of TGFB2 expression, perhaps acting in concert with GATA4 in the developing outflow tract myocardium (By similarity). Plays a role in limb pattern formation (PubMed:29726930). Acts as a transcriptional repressor of ADAM10 gene expression, perhaps in concert with histone deacetylase HDAC1 as cofactor (PubMed:30599067). Involved in branching morphogenesis in both developing lungs and adult mammary glands, via negative modulation of target genes; acting redundantly with TBX3 (By similarity). Required, together with TBX3, to maintain cell proliferation in the embryonic lung mesenchyme; perhaps acting downstream of SHH, BMP and TGFbeta signaling (By similarity). Involved in modulating early inner ear development, acting independently of, and also redundantly with TBX3, in different subregions of the developing ear (By similarity). Acts as a negative regulator of PML function in cellular senescence (PubMed:22002537). Acts as a negative regulator of expression of CDKN1A/p21, IL33 and CCN4; repression of CDKN1A is enhanced in response to UV-induced stress, perhaps as a result of phosphorylation by p38 MAPK (By similarity). Negatively modulates expression of CDKN2A/p14ARF and CDH1/E-cadherin (PubMed:11062467, PubMed:12000749, PubMed:22844464). Plays a role in induction of the epithelial-mesenchymal transition (EMT) (PubMed:22844464). Plays a role in melanocyte proliferation, perhaps via regulation of cyclin CCND1 (By similarity). Involved in melanogenesis, acting via negative modulation of expression of DHICA oxidase/TYRP1 and P protein/OCA2 (By similarity). Involved in regulating retinal pigment epithelium (RPE) cell proliferation, perhaps via negatively modulating transcription of the transcription factor CEBPD (PubMed:28910203).

关联

100 项与 TBX2 相关的临床结果

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100 项与 TBX2 相关的转化医学

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0 项与 TBX2 相关的专利（医药）

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519

项与 TBX2 相关的文献（医药）

2024-02-16·Analytical chemistry

"Three-in-One" Multifunctional Hollow Nanocages with Colorimetric Photothermal Catalytic Activity for Enhancing Sensitivity in Biosensing.

Article

作者: Haiyu Wu ; Tong Bu ; Boyang Sun ; Jia Xi ; Yuanyuan Cao ; Ying Wang ; Chenyu Xuan ; Qinlin Feng ; Huiqi Yan ; Li Wang

Immunochromatographic assays (ICAs) have been widely used in the field detection of mycotoxin contaminants. Nevertheless, the lack of multisignal readout capability and the ability of signaling tags to maintain their biological activity while efficiently loading antibodies remain a great challenge in satisfying diverse testing demands. Herein, we proposed a novel three-in-one multifunctional hollow vanadium nanomicrosphere (high brightness-catalytic-photothermal properties)-mediated triple-readout ICA (VHMS-ICA) for sensitive detection of T-2. As the key to this biosensing strategy, vanadium was used as the catalytic-photothermal characterization center, and natural polyphenols were utilized as the bridging ligands for coupling with the antibody while self-assembling with formaldehyde cross-linking into a hollow nanocage-like structure, which offers the possibility of realizing a three-signal readout strategy and improving the coupling efficiency to the antibody while preserving its biological activity. The constructed sensors showed a detection limit (LOD) of 2 pg/mL for T-2, which was about 345-fold higher than that of conventional gold nanoparticle-based ICA (0.596 ng/mL). As anticipated, the detection range of VHMS-ICA was extended about 8-fold compared with the colorimetric signal alone. Ultimately, the proposed immunosensor performed well in maize and oat samples, with satisfactory recoveries. Owing to the synergistic and complementary interactions between distinct signaling modes, the establishment of multimodal immunosensors with multifunctional tags is an efficient strategy to satisfy diversified detection demands.

2024-02-10·Cell stem cell

Canonical Wnt signaling directs the generation of functional human PSC-derived atrioventricular canal cardiomyocytes in bioprinted cardiac tissues.

Article

作者: Chenxi Ye ; Chuanlai Yang ; Heqiang Zhang ; Rui Gao ; Yingnan Liao ; Yali Zhang ; Lingjun Jie ; Yanhui Zhang ; Tong Cheng ; Yan Wang ; Jie Ren

The creation of a functional 3D bioprinted human heart remains challenging, largely due to the lack of some crucial cardiac cell types, including the atrioventricular canal (AVC) cardiomyocytes, which are essential to slow down the electrical impulse between the atrium and ventricle. By utilizing single-cell RNA sequencing analysis and a 3D bioprinting technology, we discover that stage-specific activation of canonical Wnt signaling creates functional AVC cardiomyocytes derived from human pluripotent stem cells. These cardiomyocytes display morphological characteristics and express molecular markers of AVC cardiomyocytes, including transcription factors TBX2 and MSX2. When bioprinted in prefabricated cardiac tissues, these cardiomyocytes successfully delay the electrical impulse, demonstrating their capability of functioning as the AVC cardiomyocytes in vitro. Thus, these findings not only identify canonical Wnt signaling as a key regulator of the AVC cardiomyocyte differentiation in vitro, but, more importantly, provide a critical cellular source for the biofabrication of a functional human heart.

2024-02-02·Science advances

Notch3 directs differentiation of brain mural cells from human pluripotent stem cell-derived neural crest.

Article

作者: Benjamin D Gastfriend ; Margaret E Snyder ; Hope E Holt ; Richard Daneman ; Sean P Palecek ; Eric V Shusta

Brain mural cells regulate development and function of the blood-brain barrier and control blood flow. Existing in vitro models of human brain mural cells have low expression of key mural cell genes, including NOTCH3. Thus, we asked whether activation of Notch3 signaling in hPSC-derived neural crest could direct the differentiation of brain mural cells with an improved transcriptional profile. Overexpression of the Notch3 intracellular domain (N3ICD) induced expression of mural cell markers PDGFRβ, TBX2, FOXS1, KCNJ8, SLC6A12, and endogenous Notch3. The resulting N3ICD-derived brain mural cells produced extracellular matrix, self-assembled with endothelial cells, and had functional K_ATP channels. ChIP-seq revealed that Notch3 serves as a direct input to relatively few genes in the context of this differentiation process. Our work demonstrates that activation of Notch3 signaling is sufficient to direct the differentiation of neural crest to mural cells and establishes a developmentally relevant differentiation protocol.

项与 TBX2 相关的新闻（医药）

2024-01-15

·生物谷

异位表达Tbx2和Atoh1诱导小鼠损伤模型的内毛细胞原位再生研究

耳蜗是听觉系统的第一级声音感受器，其内部的柯蒂氏器官有序排列着三排外毛细胞、一排内毛细胞及不同类型的支持细胞。内毛细胞负责将声波转换为电信号，并传递给螺旋神经节（听神经）。《Development》杂志在线发表了题为《In situ regeneration of inner hair cells in the damaged cochlea by temporally regulated coexpression of Atoh1 and Tbx2》的研究论文。该研究由中国科学院脑科学与智能技术卓越创新中心（神经科学研究所）、上海脑科学与类脑研究中心（上海脑中心）刘志勇研究组完成。研究团队构建了耳蜗内毛细胞特异性损伤的小鼠模型，并在该模型的基础上把幼年耳蜗支持细胞转分化为新的内毛细胞，从而实现了损伤耳蜗内源性内毛细胞后的原位再生，并对新的内毛细胞进行了全面详细的转录组学，形态学和电生理特性等分析。耳蜗是听觉系统的第一级声音感受器，其内部的柯蒂氏器官有序排列着三排外毛细胞、一排内毛细胞及不同类型的支持细胞。内毛细胞负责将声波转换为电信号，并传递给螺旋神经节（听神经）。与非哺乳类动物（如鱼类和鸟类）不同，哺乳类动物丧失了再生毛细胞的能力，因此毛细胞一旦损坏将导致不可逆的永久性耳聋。IBCs/IPhs是耳蜗支持细胞的两种亚型，它们与内毛细胞在空间位置上彼此相邻，并且在发育过程中具有相似的细胞起源。因此，IBCs/IPhs是内毛细胞再生的潜在细胞来源和基因操纵靶点(图1A)。本实验室前期通过在新生小鼠耳蜗IBCs/IPhs中条件性地异位过表达Atoh1和Tbx2，在正常（没有损伤）耳蜗内成功地将IBCs/IPhs转分化为vGlut3 新生内毛细胞。但仍有几个关键问题亟待解决：1）在内毛细胞损伤的耳蜗内，能否再生出新的内毛细胞？2）新的内毛细胞与野生型内毛细胞在转录组水平和电生理特性方面的相似度如何？3）新的内毛细胞能否实现听力的恢复或者部分恢复？为解决以上科学问题，研究人员首先构建了内毛细胞特异性损伤的小鼠模型Fgf8-DTR/ 小鼠模型。当Fgf8-DTR/ 被注射白喉毒素（DT）后，可以导致97.8%的内毛细胞死亡。为了探究损伤野生型内毛细胞能否增加支持细胞转分化为内毛细胞的效率，研究人员构建了一个能够进行精细调控基因表达的小鼠模型，Plp1-CreER ;Rosa26-Loxp-stop-Loxp-Tbx2-P2A-DHFR*Atoh1*DHFR-T2A-tdTomato/ ;Fgf8-DTR/ (简称Plp1-TAT-DTR)，并分为两组: 1)第一组作为对照组，仅在P2注射DT (图1B-B”和图2A-A’); 2)第二组在P0和P1注射他莫西芬(TMX)﹑P2注射DT，P3和P4注射甲氧苄啶(TMP,用于结合DHFR，从而瞬时稳定Atoh1的表达)，被定义为TMX/DT/TMP实验组(图1C-C”和图2B-B’)。实验结果显示，实验组有477.0±48.0个内毛细胞，远远高于对照组（17.3±4.0）。并且损伤情况下的新生内毛细胞的再生效率（73.5%±2.3%）显著高于未损伤的再生效率（29.5%±1.2%，图1D）。更为重要的是，单细胞转录组分析（图1E）和膜片钳电生理分析（图1F-G）表明新的内毛细胞和野生型的内毛图2.A-B.扫描电镜可观察到在内源内毛细胞损伤的情况下，新生内毛细胞可再生出新的纤毛结构；C-D.透射电镜可观察到新生内毛细胞有囊泡结构的产生；E.但小鼠听力未能得到有效的改善；F-H.电生理技术发现新的内毛细胞不具备机械敏感的MET通道电流。细胞具有高度的相似度（达60%以上），透射电镜可观察到新的内毛细胞囊泡结构的产生（图2C-D’）。本研究首次证明了当内源性内毛细胞受损时，新生IBCs/IPhs中异位表达Atoh1和Tbx2，可以再生出新的内毛细胞，它们在转录组和电生理水平上，与内源性内毛细胞有60%以上的相似度，并且再生效率比没有内源性内毛细胞损伤时有显著提高。图1：A.内毛细胞损伤再生的示意图；B.内毛细胞损伤小鼠模型可以高效特异的损伤内毛细胞；C.在内毛细胞损伤的情况下，异位表达Atoh1与Tbx2可再生出vGlut3 的新生内毛细胞；D.损伤情况下的再生毛细胞效率显著提高；E.转录组水平上，新生毛细胞与野生型P30内毛细胞聚为一群；F-G.新生内毛细胞的电压依赖的Ca电流与野生型内毛细胞相似。为了探讨再生出的新生内毛细胞是否具有生物学功能，研究人员通过听觉脑干反应检测并比较了Plp1-Ai9（TMX/TMP，阳性对照组）、Plp1-TAT-DTR（DT，阴性对照组）和Plp1-TAT-DTR（TMX/DT/TMP，实验组）三者之间的听力，结果显示实验组小鼠的听力未能得到恢复（图2E）。为了进一步寻找听力不能恢复的主要原因，研究人员利用电生理技术，发现新的内毛细胞不具备机械敏感电转导通道电流（图2F-H）。该发现解释了新的内毛细胞无法感知外界声音信号，无法恢复听力的原因，从而为未来如何再生出有功能的毛细胞提供了方向。图2.A-B.扫描电镜可观察到在内源内毛细胞损伤的情况下，新生内毛细胞可再生出新的纤毛结构；C-D.透射电镜可观察到新生内毛细胞有囊泡结构的产生；E.但小鼠听力未能得到有效的改善；F-H.电生理技术发现新的内毛细胞不具备机械敏感的MET通道电流。中国科学院脑科学与智能技术卓越创新中心刘志勇研究员与毕政鸿副研究员为本论文的通讯作者，刘志勇组副研究员李响为本论文的第一作者，博士研究生任旻蕙在生物信息学分析上做了大量工作，博士研究生顾云鹏和研究助理朱彤为本项目做了重要贡献，上海交通大学第九人民医院张宇博士和脑智卓越中心李杰博士共同完成电生理研究内容，脑智卓越中心副研究员李超和王广琴博士也对本项目提供了帮助，上海交通大学第九人民医院宋雷教授对本课题电生理内容给予了重要的指导。中国科学院脑智卓越中心光学平台、电镜平台、分子细胞技术平台和啮齿类实验动物平台提供了重要技术支持。该研究获得了国家自然科学基金委员会、科技部、上海市科委和中国科学院的资助。