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https://www.readbyqxmd.com/read/28671687/recurrent-spi1-pu-1-fusions-in-high-risk-pediatric-t-cell-acute-lymphoblastic-leukemia
#1
Masafumi Seki, Shunsuke Kimura, Tomoya Isobe, Kenichi Yoshida, Hiroo Ueno, Yaeko Nakajima-Takagi, Changshan Wang, Lin Lin, Ayana Kon, Hiromichi Suzuki, Yusuke Shiozawa, Keisuke Kataoka, Yoichi Fujii, Yuichi Shiraishi, Kenichi Chiba, Hiroko Tanaka, Teppei Shimamura, Kyoko Masuda, Hiroshi Kawamoto, Kentaro Ohki, Motohiro Kato, Yuki Arakawa, Katsuyoshi Koh, Ryoji Hanada, Hiroshi Moritake, Masaharu Akiyama, Ryoji Kobayashi, Takao Deguchi, Yoshiko Hashii, Toshihiko Imamura, Atsushi Sato, Nobutaka Kiyokawa, Akira Oka, Yasuhide Hayashi, Masatoshi Takagi, Atsushi Manabe, Akira Ohara, Keizo Horibe, Masashi Sanada, Atsushi Iwama, Hiroyuki Mano, Satoru Miyano, Seishi Ogawa, Junko Takita
The outcome of treatment-refractory and/or relapsed pediatric T cell acute lymphoblastic leukemia (T-ALL) is extremely poor, and the genetic basis for this is not well understood. Here we report comprehensive profiling of 121 cases of pediatric T-ALL using transcriptome and/or targeted capture sequencing, through which we identified new recurrent gene fusions involving SPI1 (STMN1-SPI1 and TCF7-SPI1). Cases positive for fusions involving SPI1 (encoding PU.1), accounting for 3.9% (7/181) of the examined pediatric T-ALL cases, showed a double-negative (DN; CD4(-)CD8(-)) or CD8(+) single-positive (SP) phenotype and had uniformly poor overall survival...
July 3, 2017: Nature Genetics
https://www.readbyqxmd.com/read/28615725/transcriptome-analysis-reveals-similarities-between-human-blood-cd3-cd56-bright-cells-and-mouse-cd127-innate-lymphoid-cells
#2
David S J Allan, Ana Sofia Cerdeira, Anuisa Ranjan, Christina L Kirkham, Oscar A Aguilar, Miho Tanaka, Richard W Childs, Cynthia E Dunbar, Jack L Strominger, Hernan D Kopcow, James R Carlyle
For many years, human peripheral blood natural killer (NK) cells have been divided into functionally distinct CD3(-) CD56(bright) CD16(-) and CD3(-) CD56(dim) CD16(+) subsets. Recently, several groups of innate lymphoid cells (ILC), distinct from NK cells in development and function, have been defined in mouse. A signature of genes present in mouse ILC except NK cells, defined by Immunological Genome Project studies, is significantly over-represented in human CD56(bright) cells, by gene set enrichment analysis...
June 14, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28604718/the-transcription-factor-runx3-guards-cytotoxic-cd8-effector-t-cells-against-deviation-towards-follicular-helper-t-cell-lineage
#3
Qiang Shan, Zhouhao Zeng, Shaojun Xing, Fengyin Li, Stacey M Hartwig, Jodi A Gullicksrud, Samarchith P Kurup, Natalija Van Braeckel-Budimir, Yao Su, Matthew D Martin, Steven M Varga, Ichiro Taniuchi, John T Harty, Weiqun Peng, Vladimir P Badovinac, Hai-Hui Xue
Activated CD8(+) T cells differentiate into cytotoxic effector (TEFF) cells that eliminate target cells. How TEFF cell identity is established and maintained is not fully understood. We found that Runx3 deficiency limited clonal expansion and impaired upregulation of cytotoxic molecules in TEFF cells. Runx3-deficient CD8(+) TEFF cells aberrantly upregulated genes characteristic of follicular helper T (TFH) cell lineage, including Bcl6, Tcf7 and Cxcr5. Mechanistically, the Runx3-CBFβ transcription factor complex deployed H3K27me3 to Bcl6 and Tcf7 genes to suppress the TFH program...
August 2017: Nature Immunology
https://www.readbyqxmd.com/read/28577307/disrupting-interactions-between-%C3%AE-catenin-and-activating-tcfs-reconstitutes-ground-state-pluripotency-in-mouse-embryonic-stem-cells
#4
Abil Saj, Sujash S Chatterjee, Bowen Zhu, Engin Cukuroglu, Tenzin Gocha, Xiaoqian Zhang, Jonathan Göke, Ramanuj DasGupta
The 2i-media, composed of two small molecule inhibitors (PD0325901 and CHIR99021) against MEK and GSK3-kinases, respectively, is known to establish naïve ground state pluripotency in mouse embryonic stem cells (mESCs). These inhibitors block MEK-mediated differentiation, while driving β-catenin dependent de-repression of pluripotency promoting targets. However, accumulating evidence suggest that β-catenin's association with activating TCFs (TCF7 and TCF7L2) can induce expression of several lineage-specific prodifferentiation genes...
June 2, 2017: Stem Cells
https://www.readbyqxmd.com/read/28490440/human-memory-cd8-t-cell-effector-potential-is-epigenetically-preserved-during-in-vivo-homeostasis
#5
Hossam A Abdelsamed, Ardiana Moustaki, Yiping Fan, Pranay Dogra, Hazem E Ghoneim, Caitlin C Zebley, Brandon M Triplett, Rafick-Pierre Sekaly, Ben Youngblood
Antigen-independent homeostasis of memory CD8 T cells is vital for sustaining long-lived T cell-mediated immunity. In this study, we report that maintenance of human memory CD8 T cell effector potential during in vitro and in vivo homeostatic proliferation is coupled to preservation of acquired DNA methylation programs. Whole-genome bisulfite sequencing of primary human naive, short-lived effector memory (TEM), and longer-lived central memory (TCM) and stem cell memory (TSCM) CD8 T cells identified effector molecules with demethylated promoters and poised for expression...
June 5, 2017: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/28437727/new-inter-correlated-genes-targeted-by-diatom-derived-polyunsaturated-aldehydes-in-the-sea-urchin-paracentrotus-lividus
#6
Nadia Ruocco, Anna Maria Fedele, Susan Costantini, Giovanna Romano, Adrianna Ianora, Maria Costantini
The marine environment is continually subjected to the action of stressors (including natural toxins), which represent a constant danger for benthic communities. In the present work using network analysis we identified ten genes on the basis of associated functions (FOXA, FoxG, GFI-1, nodal, JNK, OneCut/Hnf6, TAK1, tcf4, TCF7, VEGF) in the sea urchin Paracentrotus lividus, having key roles in different processes, such as embryonic development and asymmetry, cell fate specification, cell differentiation and morphogenesis, and skeletogenesis...
August 2017: Ecotoxicology and Environmental Safety
https://www.readbyqxmd.com/read/28430525/differential-expression-of-mir-202-and-validation-of-predicted-target-genes-in-the-skin-tissue-of-c57bl-6-black-mice-and-balb-c-white-mice
#7
Lei Qu, Jianping Li, Zhihui Zhao, Huaizhi Jiang, Qiaoling Zhang
In recent years, with the need of the fur industry to obtain greater quantities of high-quality fur and the research of hair follicle development attracting greater attention, the role of miRNAs in hair follicle development has become a field of intense interest. miRNAs are short length RNAs that affect gene regulation by binding to the 3'-untranslated region (3'UTR) of the mRNAs of certain target genes. This study predicted and validated the target genes of miR-202 in the skin tissue of C57BL/6 black mice and BALB/c white mice...
June 2017: DNA and Cell Biology
https://www.readbyqxmd.com/read/28422756/%C3%AE-catenin-and-pi3k%C3%AE-inhibition-expands-precursor-th17-cells-with-heightened-stemness-and-antitumor-activity
#8
Kinga Majchrzak, Michelle H Nelson, Jacob S Bowers, Stefanie R Bailey, Megan M Wyatt, John M Wrangle, Mark P Rubinstein, Juan C Varela, Zihai Li, Richard A Himes, Sherine S L Chan, Chrystal M Paulos
ICOS costimulation generates Th17 cells with durable memory responses to tumor. Herein, we found that ICOS induces PI3K/p110δ/Akt and Wnt/β-catenin pathways in Th17 cells. Coinhibiting PI3Kδ and β-catenin altered the biological fate of Th17 cells. Th17 cells inhibited of both pathways expressed less RORγt, which, in turn, reduced their ability to secrete IL-17. Unexpectedly, these cells were more effective (than uninhibited cells) at regressing tumor when infused into mice, leading to long-term curative responses...
April 20, 2017: JCI Insight
https://www.readbyqxmd.com/read/28299652/roles-of-runx2-in-skeletal-development
#9
Toshihisa Komori
Runx2 is the most upstream transcription factor essential for osteoblast differentiation. It regulates the expression of Sp7, the protein of which is a crucial transcription factor for osteoblast differentiation, as well as that of bone matrix genes including Spp1, Ibsp, and Bglap2. Runx2 is also required for chondrocyte maturation, and Runx3 has a redundant function with Runx2 in chondrocyte maturation. Runx2 regulates the expression of Col10a1, Spp1, Ibsp, and Mmp13 in chondrocytes. It also inhibits chondrocytes from acquiring the phenotypes of permanent cartilage chondrocytes...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/28220803/tcf7-is-suppressed-by-the-androgen-receptor-via-microrna-1-mediated-downregulation-and-is-involved-in-the-development-of-resistance-to-androgen-deprivation-in-prostate-cancer
#10
M K Siu, W-Y Chen, H-Y Tsai, H-Y Chen, J J Yin, C-L Chen, Y-C Tsai, Y-N Liu
BACKGROUND: Resistance to androgen deprivation therapy (ADT) represents a key step in the malignant progression of prostate cancer, and mutation to androgen receptor (AR) is one major driver to an androgen-independent phenotype. However, alternative oncogenic pathways that bypass AR signaling have emerged as an important mechanism promoting resistance to ADT. It is known that AR activation can prevent the interaction between β-catenin and T cell factor/lymphoid enhancer-binding factor (TCF/LEF) family, inhibiting the Wnt signaling pathway...
June 2017: Prostate Cancer and Prostatic Diseases
https://www.readbyqxmd.com/read/28217097/feedback-activation-of-basic-fibroblast-growth-factor-signaling-via-the-wnt-%C3%AE-catenin-pathway-in-skin-fibroblasts
#11
Xu Wang, Yuting Zhu, Congcong Sun, Tao Wang, Yingjie Shen, Wanhui Cai, Jia Sun, Lisha Chi, Haijun Wang, Na Song, Chao Niu, Jiayi Shen, Weitao Cong, Zhongxin Zhu, Yuanhu Xuan, Xiaokun Li, Litai Jin
Skin wound healing is a complex process requiring the coordinated behavior of many cell types, especially in the proliferation and migration of fibroblasts. Basic fibroblast growth factor (bFGF) is a member of the FGF family that promotes fibroblast migration, but the underlying molecular mechanism remains elusive. The present RNA sequencing study showed that the expression levels of several canonical Wnt pathway genes, including Wnt2b, Wnt3, Wnt11, T-cell factor 7 (TCF7), and Frizzled 8 (FZD8) were modified by bFGF stimulation in fibroblasts...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28198400/ubiquitin-c-terminal-hydrolase37-regulates-tcf7-dna-binding-for-the-activation-of-wnt-signalling
#12
Wonhee Han, Hyeyoon Lee, Jin-Kwan Han
The Tcf/Lef family of transcription factors mediates the Wnt/β-catenin pathway that is involved in a wide range of biological processes, including vertebrate embryogenesis and diverse pathogenesis. Post-translational modifications, including phosphorylation, sumoylation and acetylation, are known to be important for the regulation of Tcf/Lef proteins. However, the importance of ubiquitination and ubiquitin-mediated regulatory mechanisms for Tcf/Lef activity are still unclear. Here, we newly show that ubiquitin C-terminal hydrolase 37 (Uch37), a deubiquitinase, interacts with Tcf7 (formerly named Tcf1) to activate Wnt signalling...
February 15, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28144936/multiple-variants-in-5q31-1-are-associated-with-systemic-lupus-erythematosus-susceptibility-and-sub-phenotypes-in-the-han-chinese-population
#13
L Wen, Z Zhu, C Yang, L Liu, X Zuo, D L Morris, J Dou, L Ye, Y Cheng, H Guo, H Huang, Y Lin, C Zhu, L Tang, M Chen, Y Zhou, Y Ding, B Liang, F Zhou, J Gao, X Tang, X Zheng, W Wang, X Yin, H Tang, L Sun, S Yang, X Zhang, Y Sheng, Y Cui
BACKGROUND: A previous study provided evidence for genetic association between PPP2CA on 5q31.1 and systemic lupus erythematosus (SLE) across multi-ancestral cohorts, but failed to find significant evidence for association in the Chinese Han population. OBJECTIVE: To explore the association between this locus and SLE using data from our previously published genome-wide association study (GWAS) of SLE in Han Chinese population. METHODS: SNPs rs7726414 and rs244689 (near TCF7 and PPP2CA in 5q31...
February 1, 2017: British Journal of Dermatology
https://www.readbyqxmd.com/read/28128292/evaluation-of-10-sle-susceptibility-loci-in-asian-populations-which-were-initially-identified-in-european-populations
#14
Yue-Miao Zhang, Xu-Jie Zhou, Swapan K Nath, Celi Sun, Ming-Hui Zhao, Hong Zhang
Ten novel loci have been found to be associated with systemic lupus erythematosus (SLE) susceptibility by a recent genome-wide association study conducted in Europeans. To test their disease associations and genetic similarities/differences in Asians and Europeans, we genotyped the 10 novel single nucleotide polymorphisms (SNPs) and performed an association study. A Chinese cohort from Northern China was recruited as the discovery population, and three East Asian cohorts were included for independent replication...
January 27, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28062664/mapping-eqtls-with-rna-seq-reveals-novel-susceptibility-genes-non-coding-rnas-and-alternative-splicing-events-in-systemic-lupus-erythematosus
#15
Christopher A Odhams, Andrea Cortini, Lingyan Chen, Amy L Roberts, Ana Viñuela, Alfonso Buil, Kerrin S Small, Emmanouil T Dermitzakis, David L Morris, Timothy J Vyse, Deborah S Cunninghame Graham
Studies attempting to functionally interpret complex-disease susceptibility loci by GWAS and eQTL integration have predominantly employed microarrays to quantify gene-expression. RNA-Seq has the potential to discover a more comprehensive set of eQTLs and illuminate the underlying molecular consequence. We examine the functional outcome of 39 variants associated with Systemic Lupus Erythematosus (SLE) through the integration of GWAS and eQTL data from the TwinsUK microarray and RNA-Seq cohort in lymphoblastoid cell lines...
March 1, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/27941786/transcriptional-programs-that-control-expression-of-the-autoimmune-regulator-gene-aire
#16
Yonatan Herzig, Shir Nevo, Chamutal Bornstein, Miriam R Brezis, Sharon Ben-Hur, Aya Shkedy, Michal Eisenberg-Bord, Ben Levi, Michael Delacher, Yael Goldfarb, Eyal David, Leehee Weinberger, Sergey Viukov, Shifra Ben-Dor, Matthieu Giraud, Jacob H Hanna, Achim Breiling, Frank Lyko, Ido Amit, Markus Feuerer, Jakub Abramson
Aire is a transcriptional regulator that induces promiscuous expression of thousands of genes encoding tissue-restricted antigens (TRAs) in medullary thymic epithelial cells (mTECs). While the target genes of Aire are well characterized, the transcriptional programs that regulate its own expression have remained elusive. Here we comprehensively analyzed both cis-acting and trans-acting regulatory mechanisms and found that the Aire locus was insulated by the global chromatin organizer CTCF and was hypermethylated in cells and tissues that did not express Aire...
February 2017: Nature Immunology
https://www.readbyqxmd.com/read/27811935/integrated-computational-approach-to-the-analysis-of-rna-seq-data-reveals-new-transcriptional-regulators-of-psoriasis
#17
Alena Zolotarenko, Evgeny Chekalin, Alexandre Mesentsev, Ludmila Kiseleva, Elena Gribanova, Rohini Mehta, Ancha Baranova, Tatiana V Tatarinova, Eleonora S Piruzian, Sergey Bruskin
Psoriasis is a common inflammatory skin disease with complex etiology and chronic progression. To provide novel insights into the regulatory molecular mechanisms of the disease, we performed RNA sequencing analysis of 14 pairs of skin samples collected from patients with psoriasis. Subsequent pathway analysis and extraction of the transcriptional regulators governing psoriasis-associated pathways was executed using a combination of the MetaCore Interactome enrichment tool and the cisExpress algorithm, followed by comparison to a set of previously described psoriasis response elements...
November 4, 2016: Experimental & Molecular Medicine
https://www.readbyqxmd.com/read/27806296/opposing-development-of-cytotoxic-and-follicular-helper-cd4%C3%A2-t-cells-controlled-by-the-tcf-1-bcl6-nexus
#18
Tiziano Donnarumma, George R Young, Julia Merkenschlager, Urszula Eksmond, Nadine Bongard, Stephen L Nutt, Claude Boyer, Ulf Dittmer, Vu Thuy Khanh Le-Trilling, Mirko Trilling, Wibke Bayer, George Kassiotis
CD4(+) T cells develop distinct and often contrasting helper, regulatory, or cytotoxic activities. Typically a property of CD8(+) T cells, granzyme-mediated cytotoxic T cell (CTL) potential is also exerted by CD4(+) T cells. However, the conditions that induce CD4(+) CTLs are not entirely understood. Using single-cell transcriptional profiling, we uncover a unique signature of Granzyme B (GzmB)(+) CD4(+) CTLs, which distinguishes them from other CD4(+) T helper (Th) cells, including Th1 cells, and strongly contrasts with the follicular helper T (Tfh) cell signature...
November 1, 2016: Cell Reports
https://www.readbyqxmd.com/read/27766570/long-noncoding-rna-tcf7-promotes-invasiveness-and-self-renewal-of-human-non-small-cell-lung-cancer-cells
#19
Jinhui Wu, Dongshuang Wang
Lung cancer is the most common solid tumor and the leading cause of cancer-related death worldwide. Non-small cell lung cancer (NSCLC) represents the major histological subtype and accounts for about 80 % cases of lung cancer cases. Recently, lncRNA lncTCF7 was identified, which is highly expressed in hepatocellular carcinoma (HCC) tumors and liver cancer stem cells (CSCs). However, the role of lnTCF7 in NSCLC remains largely unknown. In this study, Gain- and loss-of-function studies demonstrated the critical role of lncTCF7 in promoting invasion and self-renewal in NSCLC cells...
January 2017: Human Cell
https://www.readbyqxmd.com/read/27764755/icariin-promotes-osteogenic-differentiation-of-rat-bone-marrow-stromal-cells-by-activating-the-er%C3%AE-wnt-%C3%AE-catenin-signaling-pathway
#20
QiuShi Wei, Jin Zhang, GuoJu Hong, ZhenQiu Chen, WeiMin Deng, Wei He, Mei Hui Chen
Icariin, the main effective component of Herba Epimedii, has been identified to regulate the osteogenic differentiation of rat bone marrow stromal cells (rBMSCs) and have potential application in preventing bone loss and promoting bone regeneration. However, the underlying signaling pathway of its osteogenic effect remains unclear. Here, we investigated whether icariin could promote osteogenesis of rBMSCs through modulating the estrogen receptor alpha (ERα) and Wnt/β-catenin signaling pathways, which implicated in rBMSCs osteogenesis...
December 2016: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
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