Tao Wang

Chinese Academy of Sciences

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Duanqing Pei

Westlake University

Keshi Chen

Chinese Academy of Sciences

Jiekai Chen

Chinese Academy of Sciences

Stephen T. Warren

Emory University

Peng Jin

Chinese PLA General Hospital

Hao Wu

Johns Hopkins University

Xingguo Liu

Guangzhou Institutes of Biomedicine and Health

Danyun Zhao

Versus Arthritis

Yi Wu

Guangzhou Institutes of Biomedicine and Health

Mei Zhong

Yunnan University

Cooperative Institutions

Chinese Academy of Sciences

142

University of Chinese Academy of Sciences

Guangzhou Institutes of Biomedicine and Health

Guangzhou Medical University

University of Hong Kong

Guangzhou Regenerative Medicine and Health Guangdong Laboratory

Sun Yat-sen University

Huazhong Agricultural University

Zhejiang University

Shanghai Jiao Tong University

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RRBS-Analyser: A Comprehensive Web Server for Reduced Representation Bisulfite Sequencing Data Analysis

Human Mutation (2013)

Tao Wang Qi Liu Xianfeng Li Xiaobing Wang Jinchen Li

In reduced representation bisulfite sequencing (RRBS), genomic DNA is digested with the restriction enzyme and then subjected to next-generation sequencing, which enables detection and quantification of DNA methylation at whole-genome scale with low cost. However, the data processing, interpretation, and analysis of the huge amounts of data generated pose a bioinformatics challenge. We developed RRBS-Analyser, a comprehensive genome-scale DNA methylation analysis server based on RRBS data. RRBS-Analyser can assess sequencing quality, generate detailed statistical information, align the bisulfite-treated short reads to reference genome, identify and annotate the methylcytosines (5mCs) and associate them with different genomic features in CG, CHG, and CHH content. RRBS-Analyser supports detection, annotation, and visualization of differentially methylated regions (DMRs) for multiple samples from nine reference organisms. Moreover, RRBS-Analyser provides researchers with detailed annotation of DMR-containing genes, which will greatly aid subsequent studies. The input of RRBS-Analyser can be raw FASTQ reads, generic SAM format, or self-defined format containing individual 5mC sites. RRBS-Analyser can be widely used by researchers wanting to unravel the complexities of DNA methylome in the epigenetic community. RRBS-Analyser is freely available at http://122.228.158.106/RRBSAnalyser/.

Analyser

Bisulfite sequencing

Bisulfite

10.1002/humu.22444

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Citations (35)

Differential Inhibition of Long Interspersed Element 1 by APOBEC3 Does Not Correlate with High-Molecular-Mass-Complex Formation or P-Body Association

Journal of Virology (2007)

Anna Maria Niewiadomska Chunjuan Tian Lindi Tan Tao Wang Phuong Thi Nguyen Sarkis

The human cytidine deaminase APOBEC3G (A3G) and other APOBEC3 proteins exhibit differential inhibitory activities against diverse endogenous retroelements and retroviruses, including Vif-deficient human immunodeficiency virus type 1. The potential inhibitory activity of human APOBEC proteins against long interspersed element 1 (LINE-1) has not been fully evaluated. Here, we demonstrate inhibition of LINE-1 by multiple human APOBEC3 cytidine deaminases, including previously unreported activity for A3DE and A3G. More ancient members of APOBEC, cytidine deaminases AID and APOBEC2, had no detectable activity against LINE-1. A3A, which did not form high-molecular-mass (HMM) complexes and interacted poorly with P bodies, was the most potent inhibitor of LINE-1. A3A specifically recognizes LINE-1 RNA but not the other cellular RNAs tested. However, in the presence of LINE-1, A3A became associated with HMM complexes containing LINE-1 RNA. The ability of A3A to recognize LINE-1 RNA required its catalytic domain and was important for its LINE-1 suppression. Although the mechanism of LINE-1 restriction did not seem to involve DNA editing, A3A inhibited the accumulation of nascent LINE-1 DNA, suggesting interference with LINE-1 reverse transcription and/or integration or intracellular movement of LINE-1 ribonucleoprotein. Thus, association with P bodies or cellular HMM complexes could not predict the potency of APOBEC3 anti-LINE-1 activities. The catalytic domain of APOBEC3 proteins may be important for proper folding and target factors such as RNA or protein interaction in addition to cytidine deamination.

Cytidine

APOBEC3G

APOBEC

10.1128/jvi.02800-06

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Citations (109)

The proteomic characteristics of airway mucus from critical ill COVID-19 patients

Research Square (Research Square) (2020)

Zili Zhang Tao Wang Fei Liu Airu Zhu Guoping Gu

Abstract Background: The pandemic of the coronavirus disease 2019 (COVID-19) has brought a global public health crisis. However, the pathogenesis underlying COVID-19 are barely understood. Methods: In this study, we performed proteomic analyses of airway mucus obtained by bronchoscopy from severe COVID-19 patients. In total, 2351 and 2073 proteins were identified and quantified in COVID-19 patients and healthy controls, respectively. Results: Among them, 92 differentiated expressed proteins (DEPs) (46 up-regulated and 46 down-regulated) were found with a fold change > 1.5 or < 0.67 and a p-value < 0.05, and 375 proteins were uniquely present in airway mucus from COVID-19 patients. Pathway and network enrichment analyses revealed that the 92 DEPs were mostly associated with metabolic, complement and coagulation cascades, lysosome, and cholesterol metabolism pathways, and the 375 COVID-19 only proteins were mainly enriched in amino acid degradation (Valine, Leucine and Isoleucine degradation), amino acid metabolism (beta-Alanine, Tryptophan, Cysteine and Methionine metabolism), oxidative phosphorylation, phagosome, and cholesterol metabolism pathways. Conclusions: This study aims to provide fundamental data for elucidating proteomic changes of COVID-19, which may implicate further investigation of molecular targets directing at specific therapy.

10.21203/rs.3.rs-52433/v1

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Toward pluripotency by reprogramming: mechanisms and application

Protein & Cell (2013)

Tao Wang Stephen T. Warren Peng Jin

Reprogramming

Epigenome

Regenerative Medicine

Cell fate determination

Epigenesis

10.1007/s13238-013-3074-1

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Citations (22)

Mea6/cTAGE5 Cooperates with TRAPPC12 to Regulate PTN Secretion and White Matter Development

Tiantian Ma Yaqing Wang Laikang Yu Tao Wang Pengyu Sun

Mutations of TRAPPC12 are associated with progressive childhood encephalopathy including abnormal white matter. However, the underlying pathogenesis is still unclear. Here, we found that Trappc12 deficiency in CG4 and oligodendrocyte progenitor cells (OPCs) affects their differentiation and maturation. In addition, TRAPPC12 interacts with Mea6/cTAGE5, and Mea6/cTAGE5 ablation in OPCs affects their proliferation and differentiation, leading to marked hypomyelination, compromised synaptic functionality, and aberrant behaviors in mice. We reveal that TRAPPC12 is associated with COPII components at ER exit site, and Mea6/cTAGE5 cKO disrupts the trafficking pathway by affecting the distribution and/or expression of TRAPPC12, SEC13, SEC31A, and SAR1. Moreover, we observed marked disturbances in the secretion of pleiotrophin (PTN) in Mea6-deficient OPCs. Notably, exogenous PTN supplementation ameliorated the differentiation deficits of these OPCs. Collectively, our findings indicate that the association between TRAPPC12 and MEA6 is important for cargo trafficking and white matter development.

White (mutation)

10.2139/ssrn.4529647

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Activation of Akt/FoxO signaling pathway contributes to induction of neuroprotection against transient global cerebral ischemia by hypoxic pre‐conditioning in adult rats

Journal of Neurochemistry (2010)

Lixuan Zhan Tao Wang Wen Li Zao C. Xu Weiwen Sun

It is well established that pre-conditioning protects neuronal injury against ischemia. However, the molecular mechanisms underlying ischemic tolerance are not completely understood. The purpose of the present study was to investigate the role of Akt/forkhead transcription factor, class O (FoxO) pathway in hypoxic pre-conditioning (HPC) using a newly developed HPC to transient global cerebral ischemia (tGCI) model in adult rats. HPC for 30-120 min significantly reduced cell death in the CA1 subregion after 10 min of tGCI. HPC was effective only when applied 1-4 days before ischemia. The maximum protection was observed with 30 min of hypoxia and 1 day interval between hypoxia and ischemia. The phosphorylated Akt and FoxOs measured by western blot and immunohistochemistry were significantly increased after hypoxia-ischemia except for a transient decrease in the HPC group. Lateral ventricular infusion of LY294002 before HPC blocked the increase in phosphorylated Akt and FoxOs and increased neuronal damage in HPC animals. These results suggest that pre-exposure to hypoxia induces protection against tGCI in adult rats. Activation of Akt results in the inactivation of FoxOs which may mediate ischemic tolerance after HPC.

Hypoxia

Ischemic Preconditioning

10.1111/j.1471-4159.2010.06816.x

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Citations (73)

Somatic cell reprogramming for regenerative medicine: SCNT vs. iPS cells

BioEssays (2012)

Guangjin Pan Tao Wang Hongjie Yao Duanqing Pei

Abstract Reprogramming of somatic cells to a pluripotent state holds huge potentials for regenerative medicine. However, a debate over which method is better, somatic cell nuclear transfer (SCNT) or induced pluripotent stem (iPS) cells, still persists. Both approaches have the potential to generate patient‐specific pluripotent stem cells for replacement therapy. Yet, although SCNT has been successfully applied in various vertebrates, no human pluripotent stem cells have been generated by SCNT due to technical, legal and ethical difficulties. On the other hand, human iPS cell lines have been reported from both healthy and diseased individuals. A recent study reported the generation of triploid human pluripotent stem cells by transferring somatic nuclei into oocytes, a variant form of SCNT. In this essay, we discuss this progress and the potentials of these two reprogramming approaches for regenerative medicine.

Reprogramming

Regenerative Medicine

10.1002/bies.201100174

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Citations (16)

Efficient Dlx2‐mediated astrocyte‐to‐neuron conversion and inhibition of neuroinflammation by NeuroD1

Developmental Neurobiology (2024)

Min‐Hui Liu Yu‐Ge Xu Xiao‐Ni Bai Jianhua Lin Zongqin Xiang

Abstract In vivo astrocyte‐to‐neuron (AtN) conversion induced by overexpression of neural transcriptional factors has great potential for neural regeneration and repair. Here, we demonstrate that a single neural transcriptional factor, Dlx2, converts mouse striatal astrocytes into neurons in a dose‐dependent manner. Lineage‐tracing studies in Aldh1l1‐CreERT2 mice confirm that Dlx2 can convert striatal astrocytes into DARPP32 + and Ctip2 + medium spiny neurons (MSNs). Time‐course studies reveal a gradual conversion from astrocytes to neurons in 1 month, with a distinct intermediate state in between astrocytes and neurons. Interestingly, when Dlx2‐infected astrocytes start to lose astrocytic markers, the other local astrocytes proliferate to maintain astrocytic levels in the converted areas. Unexpectedly, although Dlx2 efficiently reprograms astrocytes into neurons in the gray matter striatum, it also induces partial reprogramming of astrocytes in the white matter corpus callosum. Such partial reprogramming of white matter astrocytes is associated with neuroinflammation, which can be suppressed by the addition of NeuroD1. Our results highlight the importance of investigating AtN conversion in both the gray matter and white matter to thoroughly evaluate therapeutic potentials. This study also unveils the critical role of anti‐inflammation by NeuroD1 during AtN conversion.

Reprogramming

Medium spiny neuron

Gliogenesis

10.1002/dneu.22951

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Citations (1)

Coordination of Engineered Factors with TET1/2 Promotes Early-Stage Epigenetic Modification during Somatic Cell Reprogramming

Stem Cell Reports (2014)

Gengzhen Zhu Yujing Li Fei Zhu Tao Wang Wensong Jin

Somatic cell reprogramming toward induced pluripotent stem cells (iPSCs) holds great promise in future regenerative medicine. However, the reprogramming process mediated by the traditional defined factors (OSMK) is slow and extremely inefficient. Here, we develop a combination of modified reprogramming factors (OySyNyK) in which the transactivation domain of the Yes-associated protein is fused to defined factors and establish a highly efficient and rapid reprogramming system. We show that the efficiency of OySyNyK-induced iPSCs is up to 100-fold higher than the OSNK and the reprogramming by OySyNyK is very rapid and is initiated in 24 hr. We find that OySyNyK factors significantly increase Tet1 expression at the early stage and interact with Tet1/2 to promote reprogramming. Our studies not only establish a rapid and highly efficient iPSC reprogramming system but also uncover a mechanism by which engineered factors coordinate with TETs to regulate 5hmC-mediated epigenetic control.

Reprogramming

Regenerative Medicine

10.1016/j.stemcr.2014.01.012

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Citations (26)

Mouse Meningiocytes Express Sox2 and Yield High Efficiency of Chimeras after Nuclear Reprogramming with Exogenous Factors

Journal of Biological Chemistry (2008)

Dajiang Qin Yi Gan Kaifeng Shao Hao Wang Wen Li

Induced pluripotent stem cell technology, also termed iPS, is an emerging approach to reprogram cells into an embryonic stem cell-like state by viral transduction with defined combinations of factors. iPS cells share most characteristics of embryonic stem cells, counting pluripotency and self-renewal, and have so far been obtained from mouse and humans, including patients with genetic diseases. Remarkably, autologous transplantation of cell lineages derived from iPS cells will eliminate the possibility of immunological rejection, as well as current ethical issues surrounding human embryonic stem cell research. However, before iPS can be used for clinical purposes, technical problems must be overcome. Among other considerations, full and homogeneous iPS reprogramming is an important prerequisite. However, despite the fact that cells from several mouse tissues can be successfully induced to iPS, the overall efficiency of chimera formation of these clones remains low even if selection for Oct4 or Nanog expression is applied. In this report, we demonstrate that cells from the mouse meningeal membranes express elevated levels of the embryonic master regulator Sox2 and are highly amenable to iPS. Meningeal iPS clones, generated without selection, are fully and homogeneously reprogrammed based on DNA methylation analysis and 100% chimera competent. Our results define a population of somatic cells that are ready to undergo iPS, thus highlighting a very attractive cell type for iPS research and application.

Reprogramming

Homeobox protein NANOG

Chimera (genetics)

Regenerative Medicine

10.1074/jbc.m806788200

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Citations (40)