更新于：2024-09-19

TFCP2L1

更新于：2024-09-19

基本信息

别名

CP2-related transcriptional repressor 1、CRTR-1、CRTR1

+ [6]

简介

Transcription factor that facilitates establishment and maintenance of pluripotency in embryonic stem cells (ESCs) (PubMed:25215486, PubMed:26906118). With KLF2, acts as the major effector of self-renewal that mediates induction of pluripotency downstream of LIF/STAT3 and Wnt/beta-catenin signaling (By similarity). Required for normal duct development in the salivary gland and kidney (By similarity). Coordinates the development of the kidney collecting ducts intercalated (IC) and principal (PC) cells, which regulate acid-base and salt-water homeostasis, respectively (By similarity). Regulates the expression of IC genes including subunits B1 and D2 of the V-ATPase complex, OXGR1, CA12, SLC4A1, AQP6 and IC-specific transcription factor FOXI1 (By similarity). Regulates also the expression of JAG1 and subsequent notch signaling in the collecting duct (By similarity). JAG1 initiates notch signaling in PCs but inhibits notch signaling in ICs (By similarity). Acts as a transcriptional suppressor that may suppress UBP1-mediated transcriptional activation (By similarity). Modulates the placental expression of CYP11A1 (PubMed:10644752).

关联

100 项与 TFCP2L1 相关的临床结果

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100 项与 TFCP2L1 相关的转化医学

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0 项与 TFCP2L1 相关的专利（医药）

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项与 TFCP2L1 相关的文献（医药）

2024-06-01·Placenta

Fluorescence-activated nuclear sorting (FANS) of nuclei from in vitro-generated syncytiotrophoblast

Article

作者: Roberts, R Michael ; Schulz, Laura C ; Whyte, Jeffrey J ; Khan, Teka

Large, multinucleated cells, like syncytiotrophoblasts (STB), are not readily analyzed by standard methods used for single cells, such as single-cell RNA-sequencing and fluorescence-activated cellular sorting (FACS). Here we have demonstrated that fluorescence-activated nuclear sorting (FANS) is suitable to analyze nuclei from STB. Human pluripotent stem cells (PSCs) can be differentiated into a mixed trophoblast populations comprising approximately 20 % STB by treatment with BMP4 (Bone Morphogenetic Protein-4), plus A83-01 and PD173074, inhibitors of activin and FGF2 signaling, respectively (the BAP model) in about a week. Here we demonstrate that FANS can be used to separate two types of STB nuclei from the nine different clusters of trophoblast nuclei previously identified in the BAP model by single nucleus RNA sequencing (snRNAseq). Rather than using cell surface markers, as in FACS, transcription factors in various combinations were employed to target specific nuclear types. Nuclei were isolated at d 8 of BAP differentiation of H1 human embryonic stem cells and fixed in 4 % paraformaldehyde. After permeabilization in 0.1 % triton X-100, nuclei were incubated for 3 and 1 h at 4 °C with primary and secondary antibodies respectively and nuclear samples were then subjected to FANS. By using markers identified by snRNA and immunohistochemistry, nuclei were first sorted into a Topoisomerase-1, or TOP1, bright population and then into the two STB subpopulations by using antibodies to JUNB (Jun B Proto-Oncogene) and TFCP2L1 (Transcription Factor CP2 Like 1). The protocol established here is simple, straightforward, and efficient and can be used on a relatively large scale to sort individual subtypes of nuclei from mixed populations of trophoblasts for further analysis.

2024-02-01·Twin Research and Human Genetics

DNA Methylation Mediated the Association of Body Mass Index With Blood Pressure in Chinese Monozygotic Twins

Article

作者: Ning, Feng ; Zhang, Dongfeng ; Yao, Jie ; Wang, Weijing

AbstractObesity is an established risk factor for hypertension, but the mechanisms are only partially understood. We examined whether body mass index (BMI)-related DNA methylation (DNAm) variation would mediate the association of BMI with blood pressure (BP). We first conducted a genomewide DNA methylation analysis in monozygotic twin pairs to detect BMI-related DNAm variation and then evaluated the mediating effect of DNAm on the relationship between BMI and BP levels using the causal inference test (CIT) method and mediation analysis. Ontology enrichment analysis was performed for CpGs using the GREAT tool. A total of 60 twin pairs for BMI and systolic blood pressure (SBP) and 58 twin pairs for BMI and diastolic blood pressure (DBP) were included. BMI was positively associated with SBP (β = 1.86, p = .0004). The association between BMI and DNAm of 85 CpGs reached p < 1×10–4 level. Eleven BMI-related differentially methylated regions (DMRs) within LNCPRESS1, OGDHL, RNU1-44P, NPHS1, ECEL1P2, LLGL2, RNY4P15, MOGAT3, PHACTR3, and BAI2 were found. Of the 85 CpGs, 9 mapped to C10orf71-AS1, NDUFB5P1, KRT80, BAI2, ABCA2, PEX11G and FGF4 were significantly associated with SBP levels. Of the 9 CpGs, 2 within ABCA2 negatively mediated the association between BMI and SBP, with a mediating effect of −0.24 (95% CI [−0.65, −0.01]). BMI was also positively associated with DBP (β = 0.60, p = .0495). The association between BMI and DNAm of 193 CpGs reached p < 1×10−4 level. Twenty-five BMI-related DMRs within OGDHL, POU4F2, ECEL1P2, TTC6, SMPD4, EP400, TUBA1C and AGAP2 were found. Of the 193 CpGs, 33 mapped to ABCA2, ADORA2B, CTNNBIP1, KDM4B, NAA60, RSPH6A, SLC25A19 and STIL were significantly associated with DBP levels. Of the 33 CpGs, 12 within ABCA2, SLC25A19, KDM4B, PTPRN2, DNASE1, TFCP2L1, LMNB2 and C10orf71-AS1 negatively mediated the association between BMI and DBP, with a total mediation effect of −0.66 (95% CI [−1.07, −0.30]). Interestingly, BMI might also negatively mediate the association between the DNAm of most CpG mediators mentioned above and BP. The mediating effect of DNAm was also found when stratified by sex. In conclusion, DNAm variation may partially negatively mediate the association of BMI with BP. Our findings may provide new clues to further elucidate the pathogenesis of obesity to hypertension and identify new diagnostic biomarkers and therapeutic targets for hypertension.

2024-01-01·Reproduction in Domestic Animals

Exploring testicular miRNA profiles during developmental stages in Dezhou donkeys: A preliminary insight

Article

作者: Yu, Jie ; Wang, Xijun ; Dong, Hong ; Ahmed, Zulfiqar ; Ahmed, Imran ; Naseer, Zahid ; Liu, Wei ; Ahmad, Imtiaz

AbstractTesticular development and spermatogenesis are complex phenomena controlled by various genetic factors, including miRNA‐based post‐transcriptional gene expression regulation. Exploring the miRNA expression patterns during testicular development in Dezhou donkeys would enhance our understanding of equine fertility and spermatogenesis. In this investigation, we examined the testicular miRNA profiles at various stages of development. The experimental animals were divided into three groups based on their developmental stages: 2 months old (juvenile: n = 3), 12 months old (adolescent; n = 3) and 24 months old (adult; n = 3) donkeys. Total RNA was extracted from dissected testicles for miRNA sequencing and analysis. In total, 586 miRNAs, including 451 known miRNAs and 135 novel miRNAs, were identified. Among identified miRNAs, 315 displayed age‐dependent expression differences. The levels of miRNA expression in the juvenile group were significantly higher than in the adolescent or adult groups. The MiR‐483 exhibited the maximum fold change between juvenile and adolescent groups. Several screened genes, including SLC45A4 and TFCP2L1, have been linked to male reproductive pathways in donkeys. In addition, miR‐744 was predicted to regulate SPIN2B, a gene implicated in spermatocyte cell cycle progression and genomic integrity of spermatozoa. These results contribute to our comprehension of microRNA regulation during testicular development and spermatogenesis in Dezhou donkeys. The identified microRNAs and their target genes have the potential to serve as biomarkers for evaluating the reproductive capacity of stud donkeys.

项与 TFCP2L1 相关的新闻（医药）

2023-06-20

·生物谷

CXCR2表达/活性的缺失在黑色素肿瘤的关键机制

趋化因子及其受体已被证明在调节肿瘤的生长、进展、转移和对免疫治疗的反应中发挥重要作用。趋化因子及其受体已被证明在调节肿瘤的生长、进展、转移和对免疫治疗的反应中发挥重要作用。尽管趋化因子最初被认为是用于引导白细胞迁移的趋化剂，但越来越多的证据表明，它们可以调节更广泛的细胞类型中的其他功能，包括癌细胞。图片来源：https://doi-org.libproxy1.nus.edu.sg/10.1186/s12943-023-01789-9 近日，来自美国TVHS退伍军人事务部的研究者们在Molecular Cancer杂志上发表了题为“CXCR2 expression during melanoma tumorigenesis controls transcriptional programs that facilitate tumor growth”的文章，该研究提供了新的机制洞察力，揭示了黑色素瘤肿瘤前体细胞中CXCR2表达/活性的缺失如何导致肿瘤负担的减轻和抗肿瘤免疫微环境的创建。这种机制导致肿瘤抑制转录因子Tfcp2l1的表达增加，同时涉及生长调节、肿瘤抑制、干性、分化和免疫调节的基因的表达发生变化。这些基因表达的变化与包括AKT和mTOR在内的关键生长调节通路的激活减少相一致。虽然已知CXCR2趋化因子受体在肿瘤生长和治疗反应中发挥关键作用，但在诱导肿瘤形成过程中CXCR2在肿瘤前体细胞中的表达之间尚未建立直接联系。为了研究CXCR2在黑色素瘤发生中的作用，研究者建立了他莫昔芬诱导的酪氨酸酶启动子驱动的BRAFV600E/PTEN-/-/CXCR2-/-和NRASQ61R/INK4a-/-/CXCR2-/-黑色素瘤模型。此外，还研究了CXCR1/CXCR2拮抗剂SX682对BRAFV600E/Pten-/-和NRASQ61R/INK4a-/-小鼠及黑色素瘤细胞系的作用。研究者使用RNAseq、mMCP计数器、ChIPseq和qRT-PCR、流式细胞术和反向磷酸蛋白分析(RPPA)来探索CXCR2影响这些小鼠模型中黑色素瘤发生的潜在机制。在黑色素瘤诱导过程中，CXCR2的基因缺失或CXCR1/CXCR2的药物抑制导致了基因表达的关键变化，从而降低了肿瘤的发病率/生长，并提高了抗肿瘤免疫。有趣的是，在CXCR2消融后，关键的肿瘤抑制转录因子Tfcp2l1是在这三个不同的黑色素瘤模型中唯一显著诱导的log2倍变化大于2的基因。 Tfcp2l1在CXCR2扰动的三个模型中通常上调图片来源：https://doi-org.libproxy1.nus.edu.sg/10.1186/s12943-023-01789-9 本数据支持将CXCR1/CXCR2拮抗剂与黑色素瘤患者的免疫治疗相结合。与这一概念一致，我们已经证明了CXCR2的拮抗作用上调了PD-L1的表达，并增强了黑色素瘤细胞对抗PD-1的反应。此外，CXCR1/CXCR2拮抗剂联合抗PD-1目前正在进行治疗黑色素瘤的临床试验(NCT03161431)。展望未来，确定最有可能对这种联合疗法有反应的患者亚群并制定最大反应方案将是至关重要的。（生物谷 Bioon.com）参考文献 J. Yang et al. CXCR2 expression during melanoma tumorigenesis controls transcriptional programs that facilitate tumor growth. Mol Cancer. 2023 Jun 3;22(1):92. doi: 10.1186/s12943-023-01789-9.