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Article ; Online: An experimental workflow for identifying RNA m

Shi, Yue / Wu, Zeming / Zhang, Weiqi / Qu, Jing / Ci, Weimin / Liu, Guang-Hui

Journal of biological methods

2023 Volume 10, Page(s) e99010004

Abstract: ... ...

Abstract	N
Language	English
Publishing date	2023-08-25
Publishing country	United States
Document type	Journal Article
ISSN	2326-9901
ISSN (online)	2326-9901
DOI	10.14440/jbm.2023.403
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Article ; Online: Pyroptosis-Related Signature Predicts Prognosis and Immunotherapy Efficacy in Muscle-Invasive Bladder Cancer.

Zhang, Qi / Tan, Yezhen / Zhang, Jianye / Shi, Yue / Qi, Jie / Zou, Daojia / Ci, Weimin

Frontiers in immunology

2022 Volume 13, Page(s) 782982

Abstract: Pyroptosis has profound impacts on tumor cell proliferation, invasion, and metastasis and is of great clinical significance for different cancers. However, the role of pyroptosis in the progression and prognosis of muscle invasive bladder cancer (MIBC) ... ...

Abstract	Pyroptosis has profound impacts on tumor cell proliferation, invasion, and metastasis and is of great clinical significance for different cancers. However, the role of pyroptosis in the progression and prognosis of muscle invasive bladder cancer (MIBC) remains poorly characterized. Here, we collected multicenter MIBC data and performed integrated analysis to dissect the role of pyroptosis in MIBC and provide an optimized treatment for this disease. Based on transcriptomic data, we developed a novel prognostic model named the pyroptosis-related gene score (PRGScore), which summarizes immunological features, genomic alterations, and clinical characteristics associated with the pyroptosis phenotype. Samples with high PRGScore showed enhancement in CD8
MeSH term(s)	Female ; Humans ; Immunologic Factors ; Immunotherapy ; Male ; Muscles/metabolism ; Prognosis ; Pyroptosis ; Tumor Microenvironment ; Urinary Bladder Neoplasms
Chemical Substances	Immunologic Factors
Language	English
Publishing date	2022-04-11
Publishing country	Switzerland
Document type	Journal Article ; Multicenter Study
ZDB-ID	2606827-8
ISSN	1664-3224 ; 1664-3224
ISSN (online)	1664-3224
ISSN	1664-3224
DOI	10.3389/fimmu.2022.782982
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Article ; Online: Whole-Genome Mapping of Epigenetic Modification of 5-Formylcytosine at Single-Base Resolution by Chemical Labeling Enrichment and Deamination Sequencing.

Ding, Jiang-Hui / Li, Gaojie / Xiong, Jun / Liu, Fei-Long / Xie, Neng-Bin / Ji, Tong-Tong / Wang, Min / Guo, Xia / Feng, Yu-Qi / Ci, Weimin / Yuan, Bi-Feng

Analytical chemistry

2024 Volume 96, Issue 11, Page(s) 4726–4735

Abstract: DNA cytosine methylation (5-methylcytosine, 5mC) is a predominant epigenetic modification that plays a critical role in a variety of biological and pathological processes in mammals. In active DNA demethylation, the 10-11 translocation (TET) dioxygenases ...

Abstract	DNA cytosine methylation (5-methylcytosine, 5mC) is a predominant epigenetic modification that plays a critical role in a variety of biological and pathological processes in mammals. In active DNA demethylation, the 10-11 translocation (TET) dioxygenases can sequentially oxidize 5mC to generate three modified forms of cytosine, 5-hydroxymethylcytosine (5hmC), 5-formylcytosine (5fC), and 5-carboxylcytosine (5caC). Beyond being a demethylation intermediate, recent studies have shown that 5fC has regulatory functions in gene expression and chromatin organization. While some methods have been developed to detect 5fC, genome-wide mapping of 5fC at base resolution is still highly desirable. Herein, we propose a chemical labeling enrichment and deamination sequencing (CLED-seq) method for detecting 5fC in genomic DNA at single-base resolution. The CLED-seq method utilizes selective labeling and enrichment of 5fC-containing DNA fragments, followed by deamination mediated by apolipoprotein B mRNA-editing catalytic polypeptide-like 3A (APOBEC3A or A3A) and sequencing. In the CLED-seq process, while all C, 5mC, and 5hmC are interpreted as T during sequencing, 5fC is still read as C, enabling the precise detection of 5fC in DNA. Using the proposed CLED-seq method, we accomplished genome-wide mapping of 5fC in mouse embryonic stem cells. The mapping study revealed that promoter regions enriched with 5fC overlapped with H3K4me1, H3K4me3, and H3K27ac marks. These findings suggest a correlation between 5fC marks and active gene expression in mESCs. In conclusion, CLED-seq is a straightforward, bisulfite-free method that offers a valuable tool for detecting 5fC in genomes at a single-base resolution.
MeSH term(s)	Animals ; Mice ; Deamination ; Cytosine/metabolism ; Cytosine/analogs & derivatives ; Epigenesis, Genetic ; 5-Methylcytosine/metabolism ; Chromosome Mapping ; DNA/genetics ; DNA/metabolism ; DNA Methylation ; Mammals/metabolism ; Cytidine Deaminase ; Proteins
Chemical Substances	5-formylcytosine ; APOBEC3A protein, human (EC 3.5.4.5) ; Cytosine (8J337D1HZY) ; 5-Methylcytosine (6R795CQT4H) ; DNA (9007-49-2) ; Cytidine Deaminase (EC 3.5.4.5) ; Proteins
Language	English
Publishing date	2024-03-07
Publishing country	United States
Document type	Journal Article
ZDB-ID	1508-8
ISSN	1520-6882 ; 0003-2700
ISSN (online)	1520-6882
ISSN	0003-2700
DOI	10.1021/acs.analchem.4c00425
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Article ; Online: Ascorbic acid induced TET2 enzyme activation enhances cancer immunotherapy efficacy in renal cell carcinoma.

Peng, Ding / He, Anbang / He, Shiming / Ge, Guangzhe / Wang, Shuo / Ci, Weimin / Li, Xuesong / Xia, Dan / Zhou, Liqun

International journal of biological sciences

2022 Volume 18, Issue 3, Page(s) 995–1007

Abstract: Exploring the regulatory mechanism of PD-L1 in renal cancer is one of the key strategies to improve the response of renal cancer patients to checkpoint blockade therapy. In this study, the synergistic effect of ascorbic acid (vitamin C) supplementation ... ...

Abstract	Exploring the regulatory mechanism of PD-L1 in renal cancer is one of the key strategies to improve the response of renal cancer patients to checkpoint blockade therapy. In this study, the synergistic effect of ascorbic acid (vitamin C) supplementation and the impact of TET2 depletion on anti-PD-L1 therapy were determined in xenograft model experiments. Lymphocyte infiltration and chemokine expression were determined using flow cytometry and qRT-PCR. To determine the downstream targets of TET2, we performed hMeDip-seq and RNA-seq analyses. The molecular mechanism was further confirmed by hMeDip-qPCR, MeDip-qPCR, bisulfite sequencing, Western blotting, qRT-PCR and xenograft model experiments
MeSH term(s)	Ascorbic Acid/pharmacology ; Ascorbic Acid/therapeutic use ; B7-H1 Antigen/genetics ; Carcinoma, Renal Cell/drug therapy ; Carcinoma, Renal Cell/genetics ; Cell Line, Tumor ; Chemokines ; Cytokines ; DNA-Binding Proteins ; Dioxygenases/genetics ; Enzyme Activation ; Female ; Humans ; Immunotherapy/methods ; Kidney Neoplasms/drug therapy ; Male
Chemical Substances	B7-H1 Antigen ; Chemokines ; Cytokines ; DNA-Binding Proteins ; Dioxygenases (EC 1.13.11.-) ; TET2 protein, human (EC 1.13.11.-) ; Ascorbic Acid (PQ6CK8PD0R)
Language	English
Publishing date	2022-01-01
Publishing country	Australia
Document type	Journal Article
ZDB-ID	2179208-2
ISSN	1449-2288 ; 1449-2288
ISSN (online)	1449-2288
ISSN	1449-2288
DOI	10.7150/ijbs.67329
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Article ; Online: Regional gain and global loss of 5-hydroxymethylcytosine coexist in genitourinary cancers and regulate different oncogenic pathways.

Qi, Jie / Shi, Yue / Tan, Yezhen / Zhang, Qi / Zhang, Jianye / Wang, Jilu / Huang, Cong / Ci, Weimin

Clinical epigenetics

2022 Volume 14, Issue 1, Page(s) 117

Abstract: Background: DNA 5-hydroxymethylcytosine (5hmC) is produced by dynamic 5mC oxidation process contributing to tissue specification, and loss of 5hmC has been reported in multiple cancers including genitourinary cancers. However, 5hmC is also cell-type ... ...

Abstract	Background: DNA 5-hydroxymethylcytosine (5hmC) is produced by dynamic 5mC oxidation process contributing to tissue specification, and loss of 5hmC has been reported in multiple cancers including genitourinary cancers. However, 5hmC is also cell-type specific, and its variability may exist between differentiated tumor cells and cancer stem cells. Thus, cancer-associated changes in 5hmC may be contributed by distinct sets of tumor cells within the tumor tissues. Results: Here, we applied a sensitive immunoprecipitation-based method (hMeDIP-seq) to analyze 5hmC changes during genitourinary carcinogenesis (including prostate, urothelial and kidney). We confirmed the tissue-specific distribution of 5hmC in genitourinary tissues and identified regional gain and global loss of 5hmC coexisting in genitourinary cancers. The genes with gain of 5hmC during tumorigenesis were functionally enriched in regulating stemness and hypoxia, whereas were associated with poor clinical prognosis irrespective of their differences in tumor type. We identified that gain of 5hmC occurred in soft fibrin gel-induced 3D tumor spheres with a tumor-repopulating phenotype in two prostate cancer cell lines, 22RV1 and PC3, compared with conventional two-dimensional (2D) rigid dishes. Then, we defined a malignant signature derived from the differentially hydroxymethylated regions affected genes of cancer stem-like cells, which could predict a worse clinical outcome and identified phenotypically malignant populations of cells from prostate cancer tumors. Notably, an oxidation-resistant vitamin C derivative, ascorbyl phosphate magnesium, restored 5hmC and killed the cancer stem cell-like cells leading to apoptosis in prostate cancer cell lines. Conclusions: Collectively, our study dissects the regional gain of 5hmC in maintaining cancer stem-like cells and related to poor prognosis, which provides proof of concept for an epigenetic differentiation therapy with vitamin C by 5hmC reprogramming.
MeSH term(s)	5-Methylcytosine/analogs & derivatives ; Ascorbic Acid/pharmacology ; Carcinogenesis ; DNA/metabolism ; DNA Methylation ; Fibrin/metabolism ; Humans ; Magnesium ; Male ; Phosphates ; Prostatic Neoplasms/genetics ; Urogenital Neoplasms/genetics
Chemical Substances	Phosphates ; 5-hydroxymethylcytosine (1123-95-1) ; 5-Methylcytosine (6R795CQT4H) ; Fibrin (9001-31-4) ; DNA (9007-49-2) ; Magnesium (I38ZP9992A) ; Ascorbic Acid (PQ6CK8PD0R)
Language	English
Publishing date	2022-09-20
Publishing country	Germany
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2553921-8
ISSN	1868-7083 ; 1868-7075
ISSN (online)	1868-7083
ISSN	1868-7075
DOI	10.1186/s13148-022-01333-4
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Article ; Online: Vitamin C Deficiency Causes Cell Type-Specific Epigenetic Reprogramming and Acute Tubular Necrosis in a Mouse Model.

Yu, Zihui / Xu, Ziying / Liang, Yuan / Yin, Pengbin / Shi, Yue / Yu, Jiayi / Hao, Junfeng / Wang, Ting / Ci, Weimin

Journal of the American Society of Nephrology : JASN

2022 Volume 33, Issue 3, Page(s) 531–546

Abstract: Background: Vitamin C deficiency is found in patients with variable kidney diseases. However, the role of vitamin C as an epigenetic regulator in renal homeostasis and pathogenesis remains largely unknown.: Methods: We showed that vitamin C ... ...

Abstract	Background: Vitamin C deficiency is found in patients with variable kidney diseases. However, the role of vitamin C as an epigenetic regulator in renal homeostasis and pathogenesis remains largely unknown. Methods: We showed that vitamin C deficiency leads to acute tubular necrosis (ATN) using a vitamin C-deficient mouse model ( Results: Integrated evidence suggested that epigenetic modifications affected the proximal tubule cells and fenestrated endothelial cells, leading to tubule injury and hypoxia through transcriptional regulation. Strikingly, loss of DNA hydroxymethylation and DNA hypermethylation in vitamin C-deficient kidneys preceded the histologic sign of tubule necrosis, indicating the causality of vitamin C-induced epigenetic modification in ATN. Consistently, prophylactic supplementation of an oxidation-resistant vitamin C derivative, ascorbyl phosphate magnesium, promoted DNA demethylation and prevented the progression of cisplatin-induced ATN. Conclusions: Vitamin C played a critical role in renal homeostasis and pathogenesis in a mouse model, suggesting vitamin supplementation may be an approach to lower the risk of kidney injury.
MeSH term(s)	Animals ; Ascorbic Acid/pharmacology ; Ascorbic Acid Deficiency ; Disease Models, Animal ; Endothelial Cells ; Epigenesis, Genetic ; Female ; Humans ; Kidney Tubular Necrosis, Acute/etiology ; Male ; Mice ; Necrosis ; RNA
Chemical Substances	RNA (63231-63-0) ; Ascorbic Acid (PQ6CK8PD0R)
Language	English
Publishing date	2022-01-04
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1085942-1
ISSN	1533-3450 ; 1046-6673
ISSN (online)	1533-3450
ISSN	1046-6673
DOI	10.1681/ASN.2021070881
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Zs.A 3344: Show issues

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ab Jg. 2022: Lesesaal (EG)

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Article ; Online: Programming and inheritance of parental DNA methylomes in vertebrates.

Ci, Weimin / Liu, Jiang

Physiology (Bethesda, Md.)

2015 Volume 30, Issue 1, Page(s) 63–68

Abstract: 5-Methylcytosine (5mC) is a major epigenetic modification in animals. The programming and inheritance of parental DNA methylomes ensures the compatibility for totipotency and embryonic development. In vertebrates, the DNA methylomes of sperm and oocyte ... ...

Abstract	5-Methylcytosine (5mC) is a major epigenetic modification in animals. The programming and inheritance of parental DNA methylomes ensures the compatibility for totipotency and embryonic development. In vertebrates, the DNA methylomes of sperm and oocyte are significantly different. During early embryogenesis, the paternal and maternal methylomes will reset to the same state. Herein, we focus on recent advances in how offspring obtain the DNA methylation information from parents in vertebrates.
MeSH term(s)	5-Methylcytosine/metabolism ; Animals ; DNA Methylation/genetics ; Epigenesis, Genetic/genetics ; Humans ; Vertebrates/embryology ; Vertebrates/genetics
Chemical Substances	5-Methylcytosine (6R795CQT4H)
Language	English
Publishing date	2015-01
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	2158667-6
ISSN	1548-9221 ; 1548-9213
ISSN (online)	1548-9221
ISSN	1548-9213
DOI	10.1152/physiol.00037.2014
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Zs.A 2164: Show issues

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Article: Decoding the multicellular ecosystem of vena caval tumor thrombus in clear cell renal cell carcinoma by single-cell RNA sequencing

Shi, Yue / Zhang, Qi / Bi, Hai / Lu, Min / Tan, Yezhen / Zou, Daojia / Ge, Liyuan / Chen, Zhigang / Liu, Cheng / Ci, Weimin / Ma, Lulin

Genome biology. 2022 Dec., v. 23, no. 1

2022

Abstract: BACKGROUND: Vascular invasion with tumor thrombus frequently occurs in advanced renal cell carcinoma (RCC). Thrombectomy is one of the most challenging surgeries with high rate of perioperative morbidity and mortality. However, the mechanisms driving ... ...

Abstract	BACKGROUND: Vascular invasion with tumor thrombus frequently occurs in advanced renal cell carcinoma (RCC). Thrombectomy is one of the most challenging surgeries with high rate of perioperative morbidity and mortality. However, the mechanisms driving tumor thrombus formation are poorly understood which is required for designing effective therapy for eliminating tumor thrombus. RESULTS: We perform single-cell RNA sequencing analysis of 19 surgical tissue specimens from 8 clear cell renal cell carcinoma (ccRCC) patients with tumor thrombus. We observe tumor thrombus has increased tissue resident CD8⁺ T cells with a progenitor exhausted phenotype compared with the matched primary tumors. Remarkably, macrophages, malignant cells, endothelial cells and myofibroblasts from TTs exhibit enhanced remodeling of the extracellular matrix. The macrophages and malignant cells from primary tumors represent proinflammatory states, but also increase the expression of immunosuppressive markers compared to tumor thrombus. Finally, differential gene expression and interaction analyses reveal that tumor-stroma interplay reshapes the extracellular matrix in tumor thrombus associated with poor survival. CONCLUSIONS: Our comprehensive picture of the ecosystem of ccRCC with tumor thrombus provides deeper insights into the mechanisms of tumor thrombus formation, which may aid in the design of effective neoadjuvant therapy to promote downstaging of tumor thrombus and decrease the perioperative morbidity and mortality of thrombectomy.
Keywords	RNA ; ecosystems ; extracellular matrix ; gene expression regulation ; genome ; immunosuppression ; macrophages ; morbidity ; mortality ; phenotype ; renal cell carcinoma ; thrombosis
Language	English
Dates of publication	2022-12
Size	p. 87.
Publishing place	BioMed Central
Document type	Article
ZDB-ID	2040529-7
ISSN	1474-760X
ISSN	1474-760X
DOI	10.1186/s13059-022-02651-9
Database	NAL-Catalogue (AGRICOLA)

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Article: Single-Nucleotide Resolution Mapping of

Ma, Cheng-Jie / Li, Gaojie / Shao, Wen-Xuan / Min, Yi-Hao / Wang, Ping / Ding, Jiang-Hui / Xie, Neng-Bin / Wang, Min / Tang, Feng / Feng, Yu-Qi / Ci, Weimin / Wang, Yinsheng / Yuan, Bi-Feng

ACS central science

2023 Volume 9, Issue 9, Page(s) 1799–1809

Abstract: ... ...

Abstract	N
Language	English
Publishing date	2023-08-28
Publishing country	United States
Document type	Journal Article
ISSN	2374-7943
ISSN	2374-7943
DOI	10.1021/acscentsci.3c00481
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Article: Whole-Genome Sequencing of 5-Hydroxymethylcytosine at Base Resolution by Bisulfite-Free Single-Step Deamination with Engineered Cytosine Deaminase.

Xie, Neng-Bin / Wang, Min / Chen, Wei / Ji, Tong-Tong / Guo, Xia / Gang, Fang-Yin / Wang, Ya-Feng / Feng, Yu-Qi / Liang, Yuan / Ci, Weimin / Yuan, Bi-Feng

ACS central science

2023 Volume 9, Issue 12, Page(s) 2315–2325

Abstract: The epigenetic modification 5-hydroxymethylcytosine (5hmC) plays a crucial role in the regulation of gene expression. Although some methods have been developed to detect 5hmC, direct genome-wide mapping of 5hmC at base resolution is still highly ... ...

Abstract	The epigenetic modification 5-hydroxymethylcytosine (5hmC) plays a crucial role in the regulation of gene expression. Although some methods have been developed to detect 5hmC, direct genome-wide mapping of 5hmC at base resolution is still highly desirable. Herein, we proposed a single-step deamination sequencing (SSD-seq) method, designed to precisely map 5hmC across the genome at single-base resolution. SSD-seq takes advantage of a screened engineered human apolipoprotein B mRNA-editing catalytic polypeptide-like 3A (A3A) protein, known as eA3A-v10, to selectively deaminate cytosine (C) and 5-methylcytosine (5mC) but not 5hmC. During sequencing, the deaminated C and 5mC are converted to uracil (U) and thymine (T), read as T in the sequencing data. However, 5hmC remains unaffected by eA3A-v10 and is read as C during sequencing. Consequently, the presence of C in the sequence reads indicates the original 5hmC. We applied SSD-seq to generate a base-resolution map of 5hmC in human lung tissue. Our findings revealed that 5hmC was predominantly localized to CpG dinucleotides. Furthermore, the base-resolution map of 5hmC generated by SSD-seq demonstrated a strong correlation with prior ACE-seq results. The advantages of SSD-seq are its single-step process, absence of bisulfite treatment or DNA glycosylation, cost effectiveness, and ability to detect and quantify 5hmC directly at single-base resolution.
Language	English
Publishing date	2023-11-30
Publishing country	United States
Document type	Journal Article
ISSN	2374-7943
ISSN	2374-7943
DOI	10.1021/acscentsci.3c01131
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