|
|
|
题名
|
作者
|
年代
|
出处
|
被引量
|
| 1 | A novel m6A reader Prrc2a controls oligodendroglial specification and myelination显示文摘While N6-methyladenosine (m6A), the most abundant internal modification in eukaryotic mRNA, is linked to cell differentiation and tissue development, the biological significance of m6A modification in mammalian glial development remains unknown. Here, we identify a novel m6A reader, Prrc2a (Proline rich coiled-coil 2A), which controls oligodendrocyte specification and myelination. Nestin-Cre-mediated knockout of Prrc2a induces significant hypomyelination, decreased lifespan, as well as locomotive and cognitive defects in a mouse model. Further analyses reveal that Prrc2a is involved in oligodendrocyte progenitor cells (OPCs) proliferation and oligodendrocyte fate determination. Accordingly, oligodendroglial-lineage specific deletion of Prrc2a causes a similar phenotype of Nestin-Cre-mediated deletion. Combining transcriptome-wide RNA-seq, m6A-RIP-seq and Prrc2a RIP-seq analysis, we find that Olig2 is a critical downstream target gene of Prrc2a in oligodendrocyte development. Furthermore, Prrc2a stabilizes Olig2 mRNA through binding to a consensus GGACU motif in the Olig2 CDS (coding sequence) in an m6A-dependent manner. Interestingly, we also find that the m6A demethylase, Fto, erases the m6A modification of Olig2 mRNA and promotes its degradation. Together, our results indicate that Prrc2a plays an important role in oligodendrocyte specification through functioning as a novel m6A reader. These findings suggest a new avenue for the development of therapeutic strategies for hypomyelination-related neurological diseases. | Rong Wu Ang Li Baofa Sun Jian-Guang Sun Jinhua Zhang Ting Zhang Yusheng Chen Yujie Xiao Yuhao Gao Qingyang Zhang Jun Ma Xin Yang Yajin Liao Wei-Yi Lai Xiaolong Qi Shukun Wang Yousheng Shu Hai-Lin Wang Fengchao Wang Yun-Gui Yang Zengqiang Yuan | 2019 | Cell Research2019，29，1： | 32 |
| 2 | Circulating tumor DNA 5-hydroxymethylcytosine as a novel diagnostic biomarker for esophageal cancer显示文摘 | Xin Tian Baofa Sun Chuanyuan Chen Chunchun Gao Ji Zhang XingYu Lu Linchen Wang Xiangnan Li Yurong Xing Ruijuan Liu Xiao Han Zheng Qi Xiaojian Zhang Chuan He Dali Han Yun-Gui Yang Quancheng Kan | 2018 | Cell Research2018，28，5： | 12 |
| 3 | m^6A Regulates Neurogenesis and Neuronal Development by Modulating Histone Methyltransferase Ezh2显示文摘N6-methyladenosine (m6A),catalyzed by the methyltransferase complex consisting of Mettl3 and Mettl14,is the most abundant RNA modification in mRNAs and participates in diverse biological processes. However,the roles and precise mechanisms of m6A modification in regulating neuronal development and adult neurogenesis remain unclear. Here,we examined the function of Mettl3,the key component of the complex,in neuronal development and adult neurogenesis of mice. We found that the depletion of Mettl3 significantly reduced m6A levels in adult neural stem cells (aNSCs) and inhibited the proliferation of aNSCs. Mettl3 depletion not only inhibited neu-ronal development and skewed the differentiation of aNSCs more toward glial lineage,but also affected the morphological maturation of newborn neurons in the adult brain. m6A immunoprecip-itation combined with deep sequencing (MeRIP-seq) revealed that m6A was predominantly enriched in transcripts related to neurogenesis and neuronal development. Mechanistically,m6A was present on the transcripts of histone methyltransferase Ezh2,and its reduction upon Mettl3 knockdown decreased both Ezh2 protein expression and consequent H3K27me3 levels. The defects of neurogenesis and neuronal development induced by Mettl3 depletion could be rescued by Ezh2 overexpression. Collectively,our results uncover a crosstalk between RNA and histone modifica-tions and indicate that Mettl3-mediated m6A modification plays an important role in regulating neurogenesis and neuronal development through modulating Ezh2. | Junchen Chen Yi-Chang Zhang Chunmin Huang Hui Shen Baofa Sun Xuejun Cheng Yu-Jie Zhang Yun-Gui Yang Qiang Shu Ying Yang Xuekun Li | 2019 | Genomics, Proteomics & Bioinformatics2019，17，2： | 12 |
| 4 | 5-Hydroxymethylome in Circulating Cell-free DNA as A Potential Biomarker for Non-small-cell Lung Cancer显示文摘Non-small-cell lung cancer(NSCLC), the most common type of lung cancer accounting for 85% of the cases, is often diagnosed at advanced stages owing to the lack of efficient early diagnostic tools. 5-Hydroxymethylcytosine(5 hmC) signatures in circulating cell-free DNA(cfDNA) that carries the cancer-specific epigenetic patterns may represent the valuable biomarkers for discriminating tumor and healthy individuals, and thus could be potentially useful for NSCLC diagnosis. Here,we employed a sensitive and reliable method to map genome-wide 5 hmC in the cfDNA of Chinese NSCLC patients and detected a significant 5 hmC gain in both the gene bodies and promoter regions in the blood samples from tumor patients compared with healthy controls. Specifically, we identified six potential biomarkers from 66 patients and 67 healthy controls(mean decrease accuracy>3.2, P < 3.68E-19) using machine-learning-based tumor classifiers with high accuracy. Thus,the unique signature of 5 hmC in tumor patient's cfDNA identified in our study may provide valuable information in facilitating the development of new diagnostic and therapeutic modalities for NSCLC. | Ji Zhang Xiao Han Chunchun Gao Yurong Xing Zheng Qi Ruijuan Liu Yueqin Wang Xiaojian Zhang Yun-Gui Yang Xiangnan Li Baofa Sun Xin Tian | 2018 | Genomics, Proteomics & Bioinformatics2018，16，3： | 7 |
| 5 | Engineering of pre‐vascularized urethral patch with muscle flaps and hypoxia‐activated hUCMSC s improves its therapeutic outcome显示文摘 | Dongchong Sun Yong Yang Zhitao Wei Yong Xu Xu Zhang Baofa Hong | 2014 | J. Cell. Mol. Med2014，，3： | 1 |
| 6 | MUSIC based on uniform circular array and its directionfinding efficiency显示文摘 | Sun Baofa | 2013 | International Journal of Signal ProcessingSystems2013，1，2： | 1 |
您所在的机构暂未开通此部分的功能，请联系管理员