Transcriptional Regulation of Early T-Lymphocyte Development in Thymus

Bao, Xueyang; Qin, Yingyu; Lu, Linrong; Zheng, Mingzhu

doi:10.3389/fimmu.2022.884569

Cited by 10 publications

(7 citation statements)

References 85 publications

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“…Accumulating evidence has implicated critical roles for both ZMIZ proteins and Wnt/β-catenin signaling pathways in development and tumorigenesis. ZMIZ1 is a coactivator of Notch1 that induces TCF-1 to form a complex with β-catenin, leading to transcriptional activation of target genes via the classical Wnt pathway [ 55 ]. In the prostate cancer, ZMIZ2 interacts with β-catenin and improves β-catenin-mediated transcriptions [ 13 ].…”

Section: Discussionmentioning

confidence: 99%

ZMIZ2 facilitates hepatocellular carcinoma progression via LEF1 mediated activation of Wnt/β-catenin pathway

Ding,

Ning,

Kang

et al. 2024

Exp Hematol Oncol

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Background Hepatocellular carcinoma (HCC) is one of the most common malignancies with a high lethality rate. ZMIZ2 is a transcriptional co-activator implicated in various human diseases. However, the role and molecular mechanism of ZMIZ2 in HCC remains to be elucidated. Methods The expression and prognostic value of ZMIZ2 in HCC was excavated from public databases and explored by bioinformatic analysis. Then the expression of ZMIZ2 and related genes was further validated by quantitative RT-PCR, western blotting, and immunohistochemistry. Loss and gain-of-function experiments were performed in vitro and in vivo to investigate the function of ZMIZ2 in HCC. In addition, transcriptome sequencing and immunoprecipitation was conducted to explore the potential molecular mechanisms of ZMIZ2. Results ZMIZ2 was highly expressed in HCC and associated with poor prognosis. Silencing ZMIZ2 significantly inhibited HCC cell proliferation, cell cycle process, migration, and invasion in vitro, and also inhibited the progression of HCC in vivo. Additionally, ZMIZ2 expression was correlated with immune cell infiltration in HCC samples. Somatic mutation analysis showed that ZMIZ2 and TP53 mutations jointly affected the progression of HCC. Mechanistically, ZMIZ2 interacted with LEF1 to regulate malignant progression of HCC by activating the Wnt/β-catenin pathway. Conclusion ZMIZ2 was overexpressed in HCC and associated with poor prognosis. The overexpression of ZMIZ2 was corelated with malignant phenotype, and it facilitated HCC progression via LEF1-mediated activation of the Wnt/β-catenin pathway. Furthermore, ZMIZ2 could be served as a prognostic biomarker and a new therapeutic target for HCC.

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Section: Discussionmentioning

confidence: 99%

ZMIZ2 facilitates hepatocellular carcinoma progression via LEF1 mediated activation of Wnt/β-catenin pathway

Ding,

Ning,

Kang

et al. 2024

Exp Hematol Oncol

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“…T cell commitment occurs at the end of the DN2 prior to entry into the DN3, and during this stage they traverse a significant proliferative expansion ( 31 ). We observed a decrease in the cell number and percentage of DN3 population in the PolG D257A/D257A mice, suggesting that the fidelity of mtDNA replication significantly affects the highly proliferative cells in the DN3 stage.…”

Section: Discussionmentioning

confidence: 99%

Effective differentiation of double negative thymocytes requires high fidelity replication of mitochondrial DNA in an age dependent manner

et al. 2023

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One of the most proliferative periods for T cells occurs during their development in the thymus. Increased DNA replication can result in increased DNA mutations in the nuclear genome, but also in mitochondrial genomes. A high frequency of mitochondrial DNA mutations can lead to abnormal mitochondrial function and have negative implications on human health. Furthermore, aging is accompanied by an increase in such mutations through oxidative damage and replication errors. Increased mitochondrial DNA mutations cause loss of mitochondrial protein function, and decrease energy production, substrates, and metabolites. Here we have evaluated the effect of increased mitochondrial DNA mutations on T cell development in the thymus. Using mice carrying a mutant mitochondrial DNA polymerase γ (PolG) that causes increased mitochondrial DNA mutations, we show that high fidelity replication of mitochondrial DNA is pivotal for proper T cell development. Reducing the fidelity of mitochondrial DNA replication results in a premature age-dependent reduction in the total number of CD4/CD8 double negative and double positive thymocytes. Analysis of mitochondrial density in thymocyte subpopulations suggests that this may be due to reduced proliferation in specific double negative stages. Taken together, this work suggests that T cell development is regulated by the ability of mitochondria to faithfully replicate their DNA.

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“…Furthermore, the differentiation of T cells recognizes and binds to the major histocompatibility complex (MHC) molecules of antigen‐presenting cells (APC) by TCRs to ensure that the immune responses generate though the specifically recognizing antigens [ 10 ]. Besides, T cells can be subcategorized into CD4 + T helper cells, CD8 + cytotoxic T cells and innate T cells, including γδ T cells, natural killer T (NKT) cells, and mucosa‐associated invariant T (MAIT) cells [ 11 ] (Figure 1 ).…”

Section: T Cell‐specific Immune Responsesmentioning

confidence: 99%

Decoding the role of immune T cells: A new territory for improvement of metabolic‐associated fatty liver disease

Liu

Ding

Bai

et al. 2023

iMeta

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Metabolic-associated fatty liver disease (MAFLD) is a new emerging concept and is associated with metabolic dysfunction, generally replacing the name of nonalcoholic fatty liver disease (NAFLD) due to heterogeneous liver condition and inaccuracies in definition. The prevalence of MAFLD is rising by year due to dietary changes, metabolic disorders, and no approved therapy, affecting a quarter of the global population and representing a major economic problem that burdens healthcare systems. Currently, in addition to the common causative factors like insulin resistance, oxidative stress, and lipotoxicity, the role of immune cells, especially T cells, played in MAFLD is increasingly being emphasized by global scholars. Based on the diverse classification and pathophysiological effects of immune T cells, we comprehensively analyzed their bidirectional regulatory effects on the hepatic inflammatory microenvironment and MAFLD progression. This interaction between MAFLD and T cells was also associated with hepatic-intestinal immune crosstalk and gut microbiota homeostasis. Moreover, we pointed out several T-cell-based therapeutic approaches including but not limited to adoptive transfer of T cells, fecal microbiota transplantation, and drug therapy, especially for natural products and Chinese herbal prescriptions. Overall, this study contributes to a better understanding of the important role of T cells played in MAFLD progression and corresponding therapeutic options and provides a potential reference for further drug development.

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Transcriptional Regulation of Early T-Lymphocyte Development in Thymus

Cited by 10 publications

References 85 publications

ZMIZ2 facilitates hepatocellular carcinoma progression via LEF1 mediated activation of Wnt/β-catenin pathway

ZMIZ2 facilitates hepatocellular carcinoma progression via LEF1 mediated activation of Wnt/β-catenin pathway

Effective differentiation of double negative thymocytes requires high fidelity replication of mitochondrial DNA in an age dependent manner

Decoding the role of immune T cells: A new territory for improvement of metabolic‐associated fatty liver disease

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