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Loss of MBD2 affects early T cell development by inhibiting the WNT signaling pathway

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单位： [1]Department of Geriatrics,Tongji Hospital,Tongji Medical College,Huazhong University of Science and Technology,Wuhan,Hubei,China [2]Department of Hematology,Tongji Hospital,Tongji Medical College,Huazhong University of Science and Technology,Wuhan,Hubei,China [3]Department of Radiology,Tongji Hospital,Tongji Medical College,Huazhong University of Science and Technology,Wuhan,Hubei,China [4]State Key Laboratory of Experimental Hematology, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin, China [5]The Center for Biomedical Research,Tongji Hospital,Tongji Medical College,Huazhong University of Science and Technology,Wuhan,China

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关键词： DNA methylation Double-negative T cell Methyl-CpG-binding domain protein 2 T cell development

摘要：

DNA methylation alters the expression of certain genes without any alteration to the DNA sequence and is a dynamic process during normal hematopoietic differentiation. As an epigenetic regulator, methyl-CpG-binding domain protein 2 (MBD2) is an important member of the MBD protein family and is acknowledged as a “reader” of DNA methylation. We used a mouse model to study the effects of MBD2 on the early development of T cells. Here, we found that MBD2 deficiency led to retardation of T cell differentiation at the DN3 stage. Meanwhile, decreased proliferative capacity and increased apoptosis were detected in Mbd2−/− DN thymocytes. Furthermore, we found the WNT pathway was significantly down-regulated in Mbd2−/− DN thymocytes: DKK1 (Dickkopf-1) expression was significantly increased, while TCF7 (transcription factor 7) and c-MYC were down-regulated. Thus, these findings established that MBD2 acted as a dominant regulator to imprint DN T cell development via the WNT pathway. © 2020 Elsevier Inc.

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出版当年[2019]版：

大类 | 3 区医学

小类 | 3 区肿瘤学 4 区细胞生物学

最新[2025]版：

大类 | 3 区生物学

小类 | 4 区细胞生物学 4 区肿瘤学

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出版当年[2018]版：

Q2 ONCOLOGY Q3 CELL BIOLOGY

最新[2023]版：

Q2 ONCOLOGY Q3 CELL BIOLOGY

影响因子： 3.3 最新[2023版] 3.3 最新五年平均 3.329 出版当年[2018版] 3.317 出版当年五年平均 3.309 出版前一年[2017版] 3.383 出版后一年[2019版]

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第一作者单位： [1]Department of Geriatrics,Tongji Hospital,Tongji Medical College,Huazhong University of Science and Technology,Wuhan,Hubei,China

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通讯机构： [2]Department of Hematology,Tongji Hospital,Tongji Medical College,Huazhong University of Science and Technology,Wuhan,Hubei,China [*1]Department of Hematology,Tongji Hospital,Tongji Medical College,Huazhong University of Science and Technology,Jiefang Road 1095#,Wuhan,Hubei,430030,China

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