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Yoo-Sun Kim, Eunju Kim, Yoon Jung Park, Yuri Kim
Neuroblastoma (NB) is childhood malignancy that retains characteristics of cancer stem cells (CSCs). Targeting the CSCs is one of the therapeutic strategies proposed to achieve complete remission of NB. β-carotene (BC), an active precursor of retinoids, is a well-known antioxidant reported to possess anti-CSCs effects. Here, we investigated the involvement of retinoic acid receptors (RARs) in the anti-CSCs effects of BC. Treatment with BC or retinoic acid (RA) upregulated RARβ mRNA expression in two NB cell lines...
October 14, 2016: Biochemical and Biophysical Research Communications
Emily Swanzey, Matthias Stadtfeld
Genomic imprinting results in the monoallelic expression of genes that encode important regulators of growth and proliferation. Dysregulation of imprinted genes, such as those within the Dlk1-Dio3 locus, is associated with developmental syndromes and specific diseases. Our ability to interrogate causes of imprinting instability has been hindered by the absence of suitable model systems. Here, we describe a Dlk1 knockin reporter mouse that enables single-cell visualization of allele-specific expression and prospective isolation of cells, simultaneously...
October 11, 2016: Development
Yvette Lahbib-Mansais, Harmonie Barasc, Maria Marti-Marimon, Florence Mompart, Eddie Iannuccelli, David Robelin, Juliette Riquet, Martine Yerle-Bouissou
BACKGROUND: To explore the relationship between spatial genome organization and gene expression in the interphase nucleus, we used a genomic imprinting model, which offers parental-specific gene expression. Using 3D FISH in porcine fetal liver cells, we compared the nuclear organization of the two parental alleles (expressed or not) of insulin-like growth factor 2 (IGF2), a paternally imprinted gene located on chromosome 2. We investigated whether its nuclear positioning favors specific locus associations...
October 1, 2016: BMC Cell Biology
H Zhang, P F Jin, L L Niu, L Li, L J Wang, Y Chen, G J Zhang, H P Zhang, T Zhong
DIO3 gene encoding type 3 iodothyronine deiodinase is an imprinted gene, located in the DLK1-DIO3 (delta-like 1 homolog-type 3 iodothyronine deiodinase) imprinted domain, and is potentially involved in degrading excessive amounts of thyroid hormone to protect embryogenesis. However, the underlying regulatory mechanism of the imprinted DIO3 gene expression during fetal and neonatal development in goats has not been elucidated. In this study, we explored the DNA methylation patterns of the caprine DIO3 intragenic CpG island and quantified gene expression level in six tissues from Chinese Nanjiang Yellow 3-day old kids...
September 2, 2016: Genetics and Molecular Research: GMR
Chun-Miao Cai, Xu Xiao, Bing-Hao Wu, Bao-Feng Wei, Ze-Guang Han
Cancer stem cells (CSCs) are responsible for tumor initiation and progression. We previously showed that Delta-like homolog 1 (DLK1) may be a therapeutic target against the CSCs of human hepatocellular carcinoma (HCC). However, the therapeutic efficacy and underlying mechanism remain unclear. Here we demonstrated that knockdown of DLK1 using a tet-inducible short hairpin RNA (shRNA) system significantly inhibited proliferation, spheroid formation and in vivo xenograft tumor growth of human HCC cells. Furthermore, in an orthotopic xenograft mouse model, adenovirus-mediated DLK1 knockdown could significantly reduce tumor size, as shown by in vivo imaging approach...
September 23, 2016: Oncotarget
Reiner Hoppe, Ping Fan, Florian Büttner, Stefan Winter, Amit K Tyagi, Heather Cunliffe, V Craig Jordan, Hiltrud Brauch
Aromatase inhibitor (AI) resistance during breast cancer treatment is mimicked by MCF-7:5C (5C) and MCF-7:2A (2A) cell lines that grow spontaneously. Survival signaling is reconfigured but cells are vulnerable to estradiol (E2)-inducible apoptosis. These model systems have alterations of stress related pathways including the accumulation of endoplasmic reticulum, oxidative, and inflammatory stress that occur prior to E2-induced apoptosis. We investigated miRNA expression profiles of 5C and 2A to characterize their AI resistance phenotypes...
September 17, 2016: Oncotarget
Haowen Qiao, Qing Cao, Yucheng Fu, Wei Guan, Fangyun Cheng, Juanjuan Wu, Xin Jia, Hongshan Chen, Yajun Zhou
Leptin, an adipocyte-derived hormone, promotes liver fibrogenesis and inhibits the expression of peroxisome-proliferator activated receptor γ (PPARγ), a key transcription factor in inhibition of hepatic stellate cell (HSC) activation, in HSCs. This research aimed to further investigate the mechanisms underlying leptin regulation of PPARγ1 in HSCs in vivo and in vitro. Results demonstrated that sex-determining region Y-box 9 (Sox9) could bind to a site around -2275 within leptin response region of PPARγ1 promoter and inhibited PPARγ1 expression...
September 2, 2016: Biochimica et Biophysica Acta
Chih-Ping Chen, Chen-Ju Lin, Schu-Rern Chern, Peih-Shan Wu, Yen-Ni Chen, Shin-Wen Chen, Chen-Chi Lee, Li-Feng Chen, Chien-Wen Yang, Wayseen Wang
OBJECTIVE: We present molecular cytogenetic characterization of a prenatally detected derivative chromosome 9 [der(9)] of unknown origin. CASE REPORT: A 35-year-old woman underwent amniocentesis at 18 weeks of gestation because of advanced maternal age, which revealed a der(9) chromosome of unknown origin. The parental karyotypes were normal. Array comparative genomic hybridization (aCGH) analysis revealed a 2.593 Mb deletion of 9p24.3-p24.2 encompassing DOCK8, KANK1, DMRT1, and VLDLR and a 16...
August 2016: Taiwanese Journal of Obstetrics & Gynecology
Gabriela Schneider, Zachariah Payne Sellers, Mariusz Z Ratajczak
No abstract text is available yet for this article.
2016: Stem Cell Investigation
Monica Colitti, Bruno Stefanon
Several natural compounds exhibit strong capacity for decreasing triglyceride accumulation, enhancing lipolysis and inducing apoptosis. The present study reports the anti-adipogenic effects of Silybum marianum (SL), Citrus aurantium (CA), Taraxacum officinale (TO), resveratrol (RE), Curcuma longa (CU), caffeine (CF), oleuropein (OL) and docosahexaenoic acid (DHA) in reducing differentiation and increasing lipolysis and apoptosis. Analyses were performed on human primary visceral pre-adipocytes after 10 (P10) and 20 (P20) days of treatment during differentiation and on mature adipocytes after 7 days of treatment (A7)...
2016: EXCLI journal
Jialiang Liang, Wei Huang, Wenfeng Cai, Lei Wang, Linlin Guo, Christian Paul, Xi-Yong Yu, Yigang Wang
Therapeutic angiogenesis has emerged as a promising strategy to regenerate the damaged blood vessels resulting from ischemic diseases such as myocardial infarction (MI). However, the functional integration of implanted endothelial cells (ECs) in infarcted heart remains challenging. We herein develop an EC generation approach by inhibiting microRNA-495 (miR-495) in human induced pluripotent stem cells (hiPSCs) and assess the angiogenic potential for MI treatment. The anti-angiogenic miR-495 belonging to Dlk1-Dio3 miR cluster was identified through expression profiling and computational analysis...
August 19, 2016: Stem Cells
Wataru Yamazaki, Tomoko Amano, Hanako Bai, Masashi Takahashi, Manabu Kawahara
Genomic imprinting is an epigenetic mechanism that switches the expression of imprinted genes involved in normal embryonic growth and development in a parent-of-origin-specific manner. Changes in DNA methylation statuses from polyploidization are a well characterized epigenetic modification in plants. However, how changes in ploidy affect both imprinted gene expression and methylation status in mammals remains unclear. To address this, we used quantitative real time PCR to analyze expression levels of imprinted genes in mouse tetraploid fetuses...
September 30, 2016: Journal of Biological Chemistry
S S Zhang, J J Tan, L Li, W T Chen, N J Han, S P Guo, S Zheng, Y Liu, Y N Gao
OBJECTIVE: To explore the expression of delta-like 1 homolog (DLK1) gene in non-small cell lung cancer (NSCLC) and its regulatory mechanism. METHODS: The expression levels of DLK1 protein in 204 NSCLC tissues were examined by immunohistochemical (IHC) staining, and the correlation between DLK1expression and clinicopathological features was analyzed. Bisulfate sequencing PCR (BSP) of DNA samples from the tumor tissues of 18 NSCLC patients was performed to evaluate the DNA methylation status of CpG island in the DLK1 promoter region, and also compared with the corresponding IHC staining of DLK1 protein in the same samples...
July 2016: Zhonghua Zhong Liu za Zhi [Chinese Journal of Oncology]
Yuk Man Lam, Yuen Fan Chan, Li Chong Chan, Ray Kit Ng
Umbilical cord blood is a valuable source of hematopoietic stem cells. While cytokine stimulation can induce ex vivo hematopoietic cell proliferation, attempts have been made to use epigenetic-modifying agents to facilitate stem cell expansion through the modulation of cellular epigenetic status. However, the potential global effect of these modifying agents on epigenome raises concerns about the functional normality of the expanded cells. We studied the ex vivo expansion of cord blood hematopoietic stem and progenitor cells (HSPCs) by histone deacetylase (HDAC) inhibitors, trichostatin A and valproic acid...
August 16, 2016: International Journal of Hematology
Daisuke Sugiyama, Yuka Tanaka, Ayako Yumine, Naoko Kojima
Erythropoiesis has classically been described as occurring in two waves: first primitive and then definitive erythropoiesis. In the mouse embryo, definitive erythropoiesis begins in the yolk sac and then shifts to the liver, spleen, and bone marrow. The fetal liver serves as the primary organ for erythroid cell expansion and maturation at mid-gestation and its mechanisms have been well investigated with special attention to niche cells expressing cytokines such as SCF, TPO and IGF2. Previously, our group reported that DLK1(+) hepatoblasts support fetal liver hematopoiesis, particularly erythropoiesis, through EPO, SCF and matrix secretion...
July 2016: [Rinshō Ketsueki] the Japanese Journal of Clinical Hematology
Norikatsu Miyoshi, Jente M Stel, Keiko Shioda, Na Qu, Junko Odahima, Shino Mitsunaga, Xiangfan Zhang, Makoto Nagano, Konrad Hochedlinger, Kurt J Isselbacher, Toshi Shioda
The genome-wide depletion of 5-methylcytosines (5meCs) caused by passive dilution through DNA synthesis without daughter strand methylation and active enzymatic processes resulting in replacement of 5meCs with unmethylated cytosines is a hallmark of primordial germ cells (PGCs). Although recent studies have shown that in vitro differentiation of pluripotent stem cells (PSCs) to PGC-like cells (PGCLCs) mimics the in vivo differentiation of epiblast cells to PGCs, how DNA methylation status of PGCLCs resembles the dynamics of 5meC erasure in embryonic PGCs remains controversial...
August 23, 2016: Proceedings of the National Academy of Sciences of the United States of America
Yanfang Huang, Xiaohong Jiang, Miao Yu, Rongfu Huang, Jianfeng Yao, Ming Li, Fangfang Zheng, Xiaoyu Yang
Somatic cell nuclear transfer is frequently associated with abnormal epigenetic modifications that may lead to the developmental failure of cloned embryos. BIX-01294 (a diazepine-quinazoline-amine derivative) is a specific inhibitor of the histone methyltransferase G9a. The aim of the present study was to investigate the effects of BIX-01294 on development, dimethylation of histone H3 at lysine 9 (H3K9), DNA methylation and the expression of imprinted genes in cloned mouse preimplantation embryos. There were no significant differences in blastocyst rates of cloned embryos treated with or without 0...
August 1, 2016: Reproduction, Fertility, and Development
Jisoo Lee, Yoo-Sun Kim, JaeHwan Lee, Seung Chul Heo, Kook Lae Lee, Sang-Woon Choi, Yuri Kim
Walnut has been known for its health benefits, including anti-cardiovascular disease and anti-oxidative properties. However, there is limited evidence elucidating its effects on cancer stem cells (CSCs) which represent a small subset of cancer cells that provide resistance against chemotherapy. This study aimed to evaluate the anti-CSCs potential of walnut phenolic extract (WPE) and its bioactive compounds, including (+)-catechin, chlorogenic acid, ellagic acid, and gallic acid. In the present study, CD133⁺CD44⁺ cells were isolated from HCT116 cells using fluorescence-activated cell sorting (FACS) and then treated with WPE...
2016: Nutrients
Sonia Molina-Pinelo, Ana Salinas, Nicolás Moreno-Mata, Irene Ferrer, Rocío Suarez, Eduardo Andrés-León, Manuel Rodríguez-Paredes, Julian Gutekunst, Eloisa Jantus-Lewintre, Carlos Camps, Amancio Carnero, Luis Paz-Ares
DNA methylation is important for gene expression and genome stability, and its disruption is thought to play a key role in the initiation and progression of cancer and other diseases. The DLK1-DIO3 cluster has been shown to be imprinted in humans, and some of its components are relevant to diverse pathological processes. The purpose of this study was to assess the methylation patterns of the DLK1-DIO3 cluster in patients with lung cancer to study its relevance in the pathogenesis of this disease. We found a characteristic methylation pattern of this cluster in smoking associated lung cancer, as compared to normal lung tissue...
July 15, 2016: Oncotarget
Ilse M van der Werf, Karin Buiting, Christina Czeschik, Edwin Reyniers, Geert Vandeweyer, Piet Vanhaesebrouck, Hermann-Josef Lüdecke, Dagmar Wieczorek, Bernhard Horsthemke, Geert Mortier, Jules G Leroy, R Frank Kooy
In approximately 20% of individuals with Kagami-Ogata syndrome (KOS14, MIM 608149), characterized by a bell-shaped thorax with coat-hanger configuration of the ribs, joint contractures, abdominal wall defects and polyhydramnios during the pregnancy, the syndrome is caused by a maternal deletion of the imprinted gene cluster in chromosome 14q32.2. Most deletions reported so far included one or both of the differentially methylated regions (DMRs) - DLK1/MEG3 IG-DMR and MEG3-DMR. We present two unrelated families with two affected siblings each, presenting with classical KOS14 due to maternally inherited microdeletions...
July 13, 2016: European Journal of Human Genetics: EJHG
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