Search Our Scientific Publications & Authors

Oncol Lett 2021 May 22;21(5):412. Epub 2021 Mar 22.

Department of Hematology, The Affiliated Hospital of Nantong University, Nantong, Jiangsu 226001, P.R. China.

Multiple myeloma (MM) remains a challenge to treat, and its precise pathogenic mechanisms have not been fully clarified. The present study aimed to evaluate the relation between long non-coding RNA transcription factor 7 (lnc-TCF7) and clinical features, as well as the prognosis of patients with MM, and to determine the effects of lnc-TCF7-knockdown on the regulation (and regulatory mechanisms) of MM progression. lnc-TCF7 expression was detected in the bone marrow plasma cells of 86 patients with MM and 30 healthy controls. Read More

Cancer Discov 2021 Apr 5. Epub 2021 Apr 5.

Pediatrics/Oncology, The Children's Hospital of Philadelphia, University of Pennsylvania

The adoptive transfer of Chimeric Antigen Receptor (CAR) T-cells represents a breakthrough in clinical oncology, yet both between- and within-patient differences in autologously-derived T cells are a major contributor to therapy failure. In order to interrogate the molecular determinants of clinical CAR T-cell persistence, we extensively characterized the pre manufacture T-cells of 71 patients with B-cell malignancies on trial to receive anti-CD19 CAR T-cell therapy. We performed RNA-Seq on sorted T-cell subsets from all 71 patients, followed by paired CITE-Seq and single-cell ATAC-Seq on T-cells from 6 of these patients. Read More

Cell Tissue Res 2021 Mar 30. Epub 2021 Mar 30.

Omics Laboratory, Animal Nutrition Division, ICAR-National Institute of Animal Nutrition and Physiology, Adugodi, Bengaluru, 560030, India.

Deciphering sperm transcriptome is the key to understanding the molecular mechanisms governing peri-fertilization, embryonic development, and pregnancy establishment. This study aimed to profile sperm transcriptome to identify signature transcripts regulating male fertility. Semen samples were collected from 47 bulls with varied fertility rates. Read More

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

Mol Metab 2021 Mar 17:101213. Epub 2021 Mar 17.

Department of Medicine, Lunenfeld-Tanenbaum Research Institute, Mt. Sinai Hospital, University of Toronto, Toronto, ON, M5G1X5, Canada. Electronic address:

Objective: Glucose-dependent insulinotropic polypeptide (GIP) and Glucagon-like peptide-1 (GLP-1) are incretin hormones that exert overlapping yet distinct actions on islet β-cells. We recently observed that GIP, but not GLP-1, upregulated islet expression of Transcription Factor 7 (TCF7), a gene expressed in immune cells and associated with the risk of developing type 1 diabetes. TCF7 has also been associated with glucose homeostasis control in the liver. 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 Nutr Biochem 2021 Mar 8;92:108627. Epub 2021 Mar 8.

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, China. Electronic address:

Previous reports have shown that plant-derived microRNAs (miRNAs) regulate mammalian gene expression through dietary intake. Our prior study found that gma-miR159a, which is abundant in soybean, significantly inhibited the proliferation of colon cancer cells. In the current study, dietary gma-miR159a was utilized to study its anti-colon cancer function in azoxymethane (AOM)/dextran sodium sulfate (DSS)-induced colon cancer mice. Read More

Blood 2021 03 10. Epub 2021 Mar 10.

Department of Pathology, St Jude Children's Research Hospital, Memphis, Tennessee, United States.

Chimeric antigen receptor T cell (CAR-T cell) therapeutic efficacy is associated with long-term T cell persistence and acquisition of memory. Memory subset formation requires TCF-1, a master transcription factor for which few regulators have been identified. Here, we demonstrate using an immune-competent mouse model of B cell acute lymphoblastic leukemia (B-ALL) that Regnase-1 deficiency promotes TCF-1 expression to enhance CAR-T cell expansion and memory-like cell formation. 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

Elife 2021 Feb 17;10. Epub 2021 Feb 17.

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

The kinase PDK1 is a crucial regulator for immune cell development by connecting PI3K to downstream AKT signaling. However, the roles of PDK1 in CD4 T cell differentiation, especially in T follicular helper (Tfh) cell, remain obscure. Here we reported PDK1 intrinsically promotes the Tfh cell differentiation and germinal center responses upon acute infection by using conditional knockout mice. Read More

Elife 2021 Feb 15;10. Epub 2021 Feb 15.

Department of Stem Cell Biology and Regenerative Medicine, Eli and Edythe Broad-CIRM Center for Regenerative Medicine and Stem Cell Research, Keck School of Medicine of the University of Southern California, Los Angeles, United States.

The canonical Wnt pathway transcriptional co-activator β-catenin regulates self-renewal and differentiation of mammalian nephron progenitor cells (NPCs). We modulated β-catenin levels in NPC cultures using the GSK3 inhibitor CHIR99021 (CHIR) to examine opposing developmental actions of β-catenin. Low CHIR-mediated maintenance and expansion of NPCs are independent of direct engagement of TCF/LEF/β-catenin transcriptional complexes at low CHIR-dependent cell-cycle targets. 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

Oncol Lett 2021 Feb 18;21(2):129. Epub 2020 Dec 18.

Department of Oncology, The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430014, P.R. China.

The aim of the present study was to investigate the association of long non-coding RNA T cell factor 7 (lncRNA TCF7) with disease risk, prognosis and its cellular function in multiple myeloma (MM). A total of 132 symptomatic patients with MM and 50 controls were enrolled. Plasma cells from patients with MM and controls were separated from bone marrow samples to detect lncRNA TCF7 expression using reverse transcription-quantitative PCR. 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

Cell Rep 2021 Jan;34(4):108674

Division of Biological Sciences, Molecular Biology Section, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093-0377, USA; Department of Cellular and Molecular Medicine, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093-0377, USA. Electronic address:

Naive and memory T cells are maintained in a quiescent state, yet capable of rapid response and differentiation to antigen challenge via molecular mechanisms that are not fully understood. In naive cells, the deletion of Foxo1 following thymic development results in the increased expression of multiple AP-1 family members, rendering T cells less able to respond to antigenic challenge. Similarly, in the absence of FOXO1, post-infection memory T cells exhibit the characteristics of extended activation and senescence. Read More

Dev Dyn 2021 Jan 15. Epub 2021 Jan 15.

Department of Human Genetics, David Geffen School of Medicine, UCLA, Los Angeles, California, USA.

Background: Genetic programs underlying preimplantation development and early lineage segregation are highly conserved across mammals. It has been suggested that nonhuman primates would be better model organisms for human embryogenesis, but a limited number of studies have investigated the monkey preimplantation development. In this study, we collect single cells from cynomolgus monkey preimplantation embryos for transcriptome profiling and compare with single-cell RNA-seq data derived from human and mouse embryos. Read More

Oncol Rep 2020 Nov 27. Epub 2020 Nov 27.

Department of Clinical Hematology, School of Laboratory Medicine, Chongqing Medical University, Chongqing 400016, P.R. China.

Clinical resistance to ABL tyrosine kinase inhibitor (TKI) imatinib remains a critical issue in the treatment of chronic myeloid leukemia (CML). Transcription factor 7 (TCF7) is one of the main Wnt/β‑catenin signaling mediators. Previous studies have shown that TCF7 is vital for tumor initiation, and targeting TCF7 can reduce drug resistance in many types of cancer. Read More

Front Cell Dev Biol 2020 14;8:592967. Epub 2020 Dec 14.

R&D, Safety Science Research, Kao Corporation, Kawasaki, Japan.

Cleft palate is one of the most frequent birth defects worldwide. It causes severe problems regarding eating and speaking and requires long-term treatment. Effective prenatal treatment would contribute to reducing the risk of cleft palate. Read More

Acta Biochim Biophys Sin (Shanghai) 2021 Jan;53(1):36-45

College of Veterinary Medicine, South China Agricultural University, Guangzhou 510642, China.

Thymic epithelial cells (TECs) are essential regulators of T-cell development and selection. miRNAs play critical roles in regulating TEC proliferation during the process of thymic aging. Our previous studies revealed that miR-199b-5p was upregulated in TECs from 1- to 3-month-old mice. Read More

Cancer Immunol Immunother 2020 Dec 4. Epub 2020 Dec 4.

Deutsches Konsortium Für Translationale Krebsforschung (DKTK), Partner Site Essen, Translational Skin Cancer Research, University of Duisburg-Essen, Universitätsstr. 1, 45141, Essen, Germany.

Background: Combined inhibition of BRAF/MEK is an established therapy for melanoma. In addition to its canonical mode of action, effects of BRAF/MEK inhibitors on antitumor immune responses are emerging. Thus, we investigated the effect of these on adaptive immune responses. Read More

Exp Cell Res 2021 01 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

Aging (Albany NY) 2020 11 7;12(21):21777-21797. Epub 2020 Nov 7.

Farm Animal Genetic Resources Exploration and Innovation Key Laboratory of Sichuan Province, Sichuan Agricultural University, Chengdu 611130, Sichuan, China.

Giant panda () is an endangered mammalian species. Exploring immune and metabolic changes that occur in giant pandas with age is important for their protection. In this study, we systematically investigated the physiological and biochemical indicators in blood, as well as the transcriptome, and methylation profiles of young, adult, and old giant pandas. Read More

Immunity 2020 11 10;53(5):971-984.e5. Epub 2020 Nov 10.

Howard Hughes Medical Institute and Immunology Program, Sloan Kettering Institute, and Ludwig Center at Memorial Sloan Kettering Cancer Center, New York, NY, USA. Electronic address:

Regulatory T (Treg) cell identity is defined by the lineage-specifying transcription factor (TF) Foxp3. Here we examined mechanisms of Foxp3 function by leveraging naturally occurring genetic variation in wild-derived inbred mice, which enables the identification of DNA sequence motifs driving epigenetic features. Chromatin accessibility, TF binding, and gene expression patterns in resting and activated subsets of Treg cells, conventional CD4 T cells, and cells expressing a Foxp3 reporter null allele revealed that the majority of Foxp3-dependent changes occurred at sites not bound by Foxp3. Read More

J Pak Med Assoc 2020 Oct;70(10):1774-1778

Department of Physiology & Cell Biology, University of Health Sciences, Lahore.

Objective: To determine the frequency and association of single nucleotide polymorphism of transcription cell factor7-like2 rs7903146 (C>T) in metabolic syndrome patients with and without acute coronary syndrome.

Methods: The cross-sectional comparative study was conducted at the University of Health Sciences, Lahore, Pakistan, from July to December 2017. Patients of metabolic syndrome with and without acute coronary syndrome were selected from Sheikh Zayed Hospital, Lahore, and the Punjab Institute of Cardiology, Lahore. Read More