Search Our Scientific Publications & Authors

Signal Transduct Target Ther 2021 03 24;6(1):126. Epub 2021 Mar 24.

Institute of Immunology PLA, Third Military Medical University, Chongqing, 400038, China.

The efficient induction and long-term persistence of pathogen-specific memory CD8 T cells are pivotal to rapidly curb the reinfection. Recent studies indicated that long-noncoding RNAs expression is highly cell- and stage-specific during T cell development and differentiation, suggesting their potential roles in T cell programs. However, the key lncRNAs playing crucial roles in memory CD8 T cell establishment remain to be clarified. Read More

Hepatology 2021 Mar 13. Epub 2021 Mar 13.

Centre de Recherche des Cordeliers, Sorbonne Université, INSERM, Université de Paris, Université Paris Nord, Functional Genomics of Solid Tumors Laboratory, Equipe Labellisée Ligue Contre le Cancer, Paris, France.

DNA methylation patterns are highly rearranged in hepatocellular carcinomas (HCCs). However, diverse sources of variation are intermingled in cancer methylomes, precluding the precise characterization of underlying molecular mechanisms. We developed a computational framework (methylation signature analysis with independent component analysis [MethICA]), leveraging independent component analysis (ICA) to disentangle the diverse processes contributing to DNA methylation changes in tumors. Read More

J Anim Breed Genet 2021 Mar 8. Epub 2021 Mar 8.

Área de Genética y Reproducción Animal, SERIDA, Gijón, Spain.

A total of 184 Djallonké (West African Dwarf) sheep of Burkina Faso were analysed for Copy Number Variations (CNV) using Ovine 50 K SNP BeadChip genotyping data and two different CNV calling platforms: PennCNV and QuantiSNP. Analyses allowed to identify a total of 63 candidate Copy Number Variations Regions (CNVR) on 11 different ovine chromosomes covering about 82.5 Mb of the sheep genome. Read More

Cell Death Differ 2021 Mar 4. Epub 2021 Mar 4.

Laboratory for Bone Metabolism, Key Laboratory for Space Biosciences and Biotechnology, School of Life Sciences, Northwestern Polytechnical University, Xi'an, Shaanxi, China.

Osteoblast differentiation leading to bone formation requires a coordinated transcriptional program. Osteoblastic cells with low level of microtubule actin crosslinking factor 1 (MACF1) show reduced osteoblast differentiation ability, however, the comprehensive mechanism of MACF1's action remains unexplored. In the current study, we found that MACF1 knockdown suppressed osteoblast differentiation by altering the transcriptome dynamics. Read More

Cell Cycle 2021 Mar-Mar;20(5-6):575-590. Epub 2021 Mar 2.

Department of Pediatric Hematology and Oncology, Children's Medical Center of Hunan Provincial People's Hospital (The First-Affiliated Hospital of Hunan Normal University), Changsha, China.

Hepatoblastoma (HB) is the most commonly seen pediatric liver malignancy. With frequent mutations in CTNNB1 gene that encodes β-catenin, hepatoblastoma has been considered as a Wnt/β-catenin-activated malignant tumor. Altered glucose metabolism upon nutrient deprivation (glucose starvation) might also be a critical event in hepatoblastoma carcinogenesis. Read More

Nat Commun 2021 02 26;12(1):1333. Epub 2021 Feb 26.

State Key Laboratory of Agrobiotechnology, College of Biological Sciences, China Agricultural University, Beijing, China.

T follicular helper (T) cells are specialized effector CD4 T cells critical to humoral immunity. Whether post-transcriptional regulation has a function in T cells is unknown. Here, we show conditional deletion of METTL3 (a methyltransferase catalyzing mRNA N-methyladenosine (mA) modification) in CD4 T cells impairs T differentiation and germinal center responses in a cell-intrinsic manner in mice. Read More

Nat Commun 2021 02 12;12(1):1009. Epub 2021 Feb 12.

Department of Pathology and Immunology, University of Geneva, Geneva, Switzerland.

Self-reactive CD8 T cells are important mediators of progressive tissue damage in autoimmune diseases, but the molecular program underlying these cells' functional adaptation is unclear. Here we characterize the transcriptional and epigenetic landscape of self-reactive CD8 T cells in a mouse model of protracted central nervous system (CNS) autoimmunity and compare it to populations of CNS-resident memory CD8 T cells emerging from acute viral infection. We find that autoimmune CD8 T cells persisting at sites of self-antigen exhibit characteristic transcriptional regulation together with distinct epigenetic remodeling. Read More

Cell Rep 2021 Feb;34(5):108716

Blood Cell Development and Function Program, Fox Chase Cancer Center, 333 Burholme Avenue, Philadelphia, PA 19111, USA. Electronic address:

TCF1 plays a critical role in T lineage commitment and the development of αβ lineage T cells, but its role in γδ T cell development remains poorly understood. Here, we reveal a regulatory axis where T cell receptor (TCR) signaling controls TCF1 expression through an E-protein-bound regulatory element in the Tcf7 locus, and this axis regulates both γδ T lineage commitment and effector fate. Indeed, the level of TCF1 expression plays an important role in setting the threshold for γδ T lineage commitment and modulates the ability of TCR signaling to influence effector fate adoption by γδ T lineage progenitors. Read More

Exp Cell Res 2021 Jan 30;398(1):112400. Epub 2020 Nov 30.

Department of Hematology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China. Electronic address:

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. Read More

Development 2020 12 24;147(24). Epub 2020 Dec 24.

Center for Precision Health, School of Biomedical Informatics, The University of Texas Health Science Center at Houston, Houston, TX 77030, USA

Craniofacial development is regulated through dynamic and complex mechanisms that involve various signaling cascades and gene regulations. Disruption of such regulations can result in craniofacial birth defects. Here, we propose the first developmental stage-specific network approach by integrating two crucial regulators, transcription factors (TFs) and microRNAs (miRNAs), to study their co-regulation during craniofacial development. Read More

PeerJ 2020 27;8:e10141. Epub 2020 Oct 27.

Department of Medical Biochemistry, Ege University Faculty of Medicine, Izmir, Turkey.

A comprehensive meta-analysis of publicly available gene expression microarray data obtained from human-derived pancreatic ductal adenocarcinoma (PDAC) tissues and their histologically matched adjacent tissue samples was performed to provide diagnostic and prognostic biomarkers, and molecular targets for PDAC. An integrative meta-analysis of four submissions (GSE62452, GSE15471, GSE62165, and GSE56560) containing 105 eligible tumor-adjacent tissue pairs revealed 344 differentially over-expressed and 168 repressed genes in PDAC compared to the adjacent-to-tumor samples. The validation analysis using TCGA combined GTEx data confirmed 98. Read More

Biochem Biophys Res Commun 2021 01 13;534:727-733. Epub 2020 Nov 13.

Department of Oral & Cranio-Maxillofacial Surgery, Shanghai Ninth People's Hospital, College of Stomatology, Shanghai Jiao Tong University School of Medicine, National Clinical Research Center for Oral Diseases, Shanghai Key Laboratory of Stomatology & Shanghai Research Institute of Stomatology, Shanghai, 200011, China. Electronic address:

Osteoporosis is a common skeletal complication of diabetes mellitus (DM). The mechanisms underlying the pathophysiology of diabetic osteoporosis are complex. Glycogen synthase kinase-3β (GSK-3β) is a widely expressed serine/threonine kinase and associated with both DM and bone metabolism, which arouse our concern. Read More

Nat Immunol 2021 01 2;22(1):41-52. Epub 2020 Nov 2.

Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.

Personalized cancer vaccines are a promising approach for inducing T cell immunity to tumor neoantigens. Using a self-assembling nanoparticle vaccine that links neoantigen peptides to a Toll-like receptor 7/8 agonist (SNP-7/8a), we show how the route and dose alter the magnitude and quality of neoantigen-specific CD8 T cells. Intravenous vaccination (SNP-IV) induced a higher proportion of TCF1PD-1CD8 T cells as compared to subcutaneous immunization (SNP-SC). Read More

Eur Rev Med Pharmacol Sci 2020 09;24(18):9633-9644

Department of Cardiac Surgery, The First Hospital of Jilin University, Jilin, China.

Objective: Atherosclerosis is an inflammation-associated disease resulting in a huge health hazard. Abundance of researches showed that long non-coding RNAs (lncRNAs) played vital roles in atherosclerosis, but the molecular mechanism of nuclear-enriched abundant transcript (NEAT1) has not been fully elucidated yet.

Patients And Methods: Human umbilical vein endothelial cells (HUVECs) were treated with oxidized low-density lipoprotein (ox-LDL) for constructing the model of atherosclerosis. Read More

Anticancer Agents Med Chem 2020 Sep 30. Epub 2020 Sep 30.

Department of Radiotherapy, Oncology Department, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi Province. China.

Background: G protein-coupled receptor 4 (GPR4) has been reported to play an essential role in regulating the proliferation, migration and angiogenesis of vascular endothelial cells. GPR4 is also suggested play roles in the growth and angiogenesis of ovarian cancer.

Objective: To explore the function of GPR4 and transcription factor 7 (TCF7) in ovarian cancer. Read More

Cancer Biother Radiopharm 2020 Aug 19. Epub 2020 Aug 19.

Department of Thoracic Surgery, Chengdu Second People's Hospital, Chengdu, China.

The procancer effect of TEA domain transcription factor 4 () has been gradually discovered. However, its expression in esophageal cancer (EC) cells and its effect on proliferation and apoptosis have not been reported. In this study, we investigated the possible role of in EC cells. Read More

Cancer Res 2020 10 19;80(20):4451-4464. Epub 2020 Aug 19.

Division of Cancer Differentiation, National Cancer Center, Tokyo, Japan.

Cancer chemoresistance is often attributed to the presence of cancer stem cell (CSC)-like cells, but whether they are homogeneously chemoresistant remains unclear. We previously showed that in colon tumors, a subpopulation of CSC-like cells driven by TCF1 (TCF7), a Wnt-responsive transcription factor, were responsible for tumorigenicity. Here we demonstrate that the tumorigenic subpopulation of mouse cells exists in a slow-cycling state and identify a unique 22-gene signature that characterizes these slow-cycling CSC. Read More

PLoS Pathog 2020 08 6;16(8):e1008678. Epub 2020 Aug 6.

IrsiCaixa AIDS Research Institute, Hospital Germans Trias i Pujol, Institute for Health Science Research Germans Trias i Pujol (IGTP), Badalona, Spain.

GWAS, immune analyses and biomarker screenings have identified host factors associated with in vivo HIV-1 control. However, there is a gap in the knowledge about the mechanisms that regulate the expression of such host factors. Here, we aimed to assess DNA methylation impact on host genome in natural HIV-1 control. Read More

J Immunol 2020 09 3;205(5):1419-1432. Epub 2020 Aug 3.

Department of Biomedical and Clinical Sciences, Linköping University, 581 85 Linköping, Sweden.

Maturation of lymphoid cells is controlled by the action of stage and lineage-restricted transcription factors working in concert with the general transcription and chromatin remodeling machinery to regulate gene expression. To better understand this functional interplay, we used Biotin Identification in human embryonic kidney cells to identify proximity interaction partners for GATA3, TCF7 (TCF1), SPI1, HLF, IKZF1, PAX5, ID1, and ID2. The proximity interaction partners shared among the lineage-restricted transcription factors included ARID1a, a BRG1-associated factor complex component. Read More

Carcinogenesis 2021 Feb;42(1):148-158

Department of Molecular-Targeting Prevention, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kawaramachi-Hirokoji, Kamigyo-ku, Kyoto, Japan.

Artesunate (ART) is a clinically approved antimalarial drug and was revealed as a candidate of colorectal cancer chemopreventive agents in our drug screening system. Here, we aimed to understand the suppressive effects of ART on intestinal tumorigenesis. In vitro, ART reduced T-cell factor/lymphoid enhancer factor (TCF/LEF) promoter transcriptional activity. Read More

PLoS Biol 2020 07 23;18(7):e3000561. Epub 2020 Jul 23.

State Key Laboratory of Freshwater Ecology and Biotechnology, Institute of Hydrobiology, Innovation Academy for Seed Design, Chinese Academy of Sciences, Wuhan, China.

Maternal β-catenin activity is essential and critical for dorsal induction and its dorsal activation has been thoroughly studied. However, how the maternal β-catenin activity is suppressed in the nondorsal cells remains poorly understood. Nanog is known to play a central role for maintenance of the pluripotency and maternal -zygotic transition (MZT). Read More

PLoS Pathog 2020 06 24;16(6):e1008555. Epub 2020 Jun 24.

Department of Immunology, Erasmus University Medical Center, Rotterdam, The Netherlands.

Exhaustion is a dysfunctional state of cytotoxic CD8+ T cells (CTL) observed in chronic infection and cancer. Current in vivo models of CTL exhaustion using chronic viral infections or cancer yield very few exhausted CTL, limiting the analysis that can be done on these cells. Establishing an in vitro system that rapidly induces CTL exhaustion would therefore greatly facilitate the study of this phenotype, identify the truly exhaustion-associated changes and allow the testing of novel approaches to reverse or prevent exhaustion. Read More

Cell Immunol 2020 07 6;353:104118. Epub 2020 May 6.

Guangdong Province Key Laboratory of Biotechnology Drug Candidates, Guangdong Pharmaceutical University, Guangzhou, China; School of Life Sciences and Biopharmaceutics, Guangdong Pharmaceutical University, Guangzhou, China. Electronic address:

The in vivo proliferation and viability of transfused engineered T cells markedly limits the long-term effect of adoptive cell therapy on tumors. The therapeutic efficacy and proliferative potential of T cells are reported to be dependent on the differentiation status of T cells. The T cells at the early stage of progressive differentiation have a long lifespan, strong proliferative potential, and the ability to reconstruct intact T cell subsets. Read More

Genomics 2020 09 11;112(5):2949-2958. Epub 2020 May 11.

College of Food Science and Engineering, Collaborative Innovation Center for Modern Grain Circulation and Safety, Key Laboratory of Grains and Oils Quality Control and Processing, Nanjing University of Finance and Economics, Nanjing 210046, China. Electronic address:

MicroRNAs (miRNAs) are important regulators of gene expression in eukaryotes. Studies have shown that plant-derived miRNAs can be absorbed through diets and regulate gene expression in mammals. Although soybean-derived miRNAs have been reported, their biological functions are still unclear. Read More

Genes (Basel) 2020 05 11;11(5). Epub 2020 May 11.

Institute of Medical Sciences, University of Aberdeen, Aberdeen AB25 2ZD, Scotland, UK.

Aberrantly activated Wnt signaling causes cellular transformation that can lead to human colorectal cancer. Wnt signaling is mediated by Lymphoid Enhancer Factor/T-Cell Factor (LEF/TCF) DNA-binding factors. Here we investigate whether altered / expression is conserved in human colorectal tumor sample and may potentially be correlated with indicators of cancer progression. Read More

Onco Targets Ther 2020 16;13:3223-3235. Epub 2020 Apr 16.

Medical College, Qingdao University, Qingdao, Shandong, People's Republic of China.

Introduction: Colorectal cancer, one of the most common tumors, is mainly fatal because of the occurrence of liver metastasis. Inositol hexaphosphate (IP6) and inositol (INS) were found, both, in vitro and in vivo to play an anti-tumor effect, whereas the combination of IP6 and INS was more effective than IP6 or INS alone.

Materials and methods: The inhibitory effects of IP6, INS and the combination of IP6+INS on tumor progression and liver metastasis of colorectal cancer were investigated in an orthotopic transplantation model of colorectal cancer. Read More

Int J Mol Sci 2020 Apr 12;21(8). Epub 2020 Apr 12.

Basic and Translational Research Center for Hard Tissue Disease, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki 852-8588, Japan.

Runx2 is required for chondrocyte proliferation and maturation. In the search of Runx2 target genes in chondrocytes, we found that Runx2 up-regulated the expression of hematopoietic cell kinase (, which is a member of the Src tyrosine kinase family, in chondrocytes, that expression was high in cartilaginous limb skeletons of wild-type mice but low in those of mice, and that Runx2 bound the promoter region of . To investigate the functions of Hck in chondrocytes, transgenic mice expressing a constitutively active form of () were generated using the promoter/enhancer. Read More

Cell Rep 2020 04;31(1):107484

T Cell Metabolism Group (D140), German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, 69120 Heidelberg, Germany; Faculty of Biosciences, Heidelberg University, 69120 Heidelberg, Germany. Electronic address:

T cell factor 1 (Tcf1) promotes the central memory CD8 T (T) cell differentiation and stemness in lymphoid tissues after systemic infections. It remains unclear whether Tcf1 regulates the CD103 tissue-resident memory CD8 T (T) cell formation in non-lymphoid tissues after mucosal infections. We find that Tcf1 is progressively decreased during lung T cell formation. Read More

Front Immunol 2020 20;11:470. Epub 2020 Mar 20.

T-Cell Biology and Development Unit, Laboratory of Genome Integrity, Center for Cancer Research, National Cancer Institute, National Institute of Health, Bethesda, MD, United States.

The transcription factor TCF-1 (encoded by ) plays critical roles in several lineages of hematopoietic cells. In this study, we examined the molecular basis for regulation in T cells, innate lymphoid cells, and migratory conventional dendritic cells that we find express . We identified a 1 kb regulatory element crucial for the initiation of expression in T cells and innate lymphoid cells, but dispensable for expression in -expressing dendritic cells. Read More

Exp Ther Med 2020 Apr 21;19(4):2913-2922. Epub 2020 Feb 21.

Department of Cardiothoracic Surgery, Zhuji People's Hospital, Zhuji, Zhejiang 311800, P.R. China.

The efficacy of ginsenoside Rh2 (Rh2) in cancer therapy has been reported; however, its function in lung cancer remains unknown. To analyze the role of Rh2 in the inhibition of lung cancer cell proliferation in the present study, protein expression levels of E-cadherin, vimentin, β-catenin, Smo, Gli1, and α-catenin were assessed by western blotting, whilst mRNA expression levels of , , , , and were determined by reverse transcription-quantitative PCR in the A549 cell line. Phosphorylation sites were detected by proteomic methods and cell proliferation was analyzed by MTT assay. Read More