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https://www.readbyqxmd.com/read/29069662/af1q-contributes-to-adriamycin-induced-podocyte-injury-by-activating-wnt-%C3%AE-catenin-signaling
#1
Hongbo Zhang, Rui Ren, Juan Du, Tingli Sun, Ping Wang, Ping Kang
BACKGROUND/AIMS: Injury of podocytes plays an important role in decline of glomerular filtration and proteinuria. It is well-known that proteinuria is associated with numerous chronic kidney diseases (CKD). However, the underlying mechanism of podocyte injury remains unclear. METHODS: We used reverse transcription-quantitative PCR (RT-qPCR) to compare the expression level of the ALL1-fused from the chromosome 1q (AF1q) gene in mice and mouse podocytes (MPC5) with or without Adriamycin (ADR) treatment...
October 25, 2017: Kidney & Blood Pressure Research
https://www.readbyqxmd.com/read/29033940/pi3k%C3%AE-inhibition-enhances-the-antitumor-fitness-of-adoptively-transferred-cd8-t-cells
#2
Jacob S Bowers, Kinga Majchrzak, Michelle H Nelson, Bulent Arman Aksoy, Megan M Wyatt, Aubrey S Smith, Stefanie R Bailey, Lillian R Neal, Jeffrey E Hammerbacher, Chrystal M Paulos
Phosphatidylinositol-3-kinase p110δ (PI3Kδ) inhibition by Idelalisib (CAL-101) in hematological malignancies directly induces apoptosis in cancer cells and disrupts immunological tolerance by depleting regulatory T cells. Yet, little is known about the direct impact of PI3Kδ blockade on effector T cells from CAL-101 therapy. Herein, we demonstrate a direct effect of p110δ inactivation via CAL-101 on murine and human CD8(+) T cells that promotes a strong undifferentiated phenotype (elevated CD62L/CCR7, CD127, and Tcf7)...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28973925/foxo1-opposition-of-cd8-t-cell-effector-programming-confers-early-memory-properties-and-phenotypic-diversity
#3
Arnaud Delpoux, Chen-Yen Lai, Stephen M Hedrick, Andrew L Doedens
The factors and steps controlling postinfection CD8(+) T cell terminal effector versus memory differentiation are incompletely understood. Whereas we found that naive TCF7 (alias "Tcf-1") expression is FOXO1 independent, early postinfection we report bimodal, FOXO1-dependent expression of the memory-essential transcription factor TCF7 in pathogen-specific CD8(+) T cells. We determined the early postinfection TCF7(high) population is marked by low TIM3 expression and bears memory signature hallmarks before the appearance of established memory precursor marker CD127 (IL-7R)...
October 17, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28930662/the-kinase-mtorc1-promotes-the-generation-and-suppressive-function-of-follicular-regulatory-t-cells
#4
Lifan Xu, Qizhao Huang, Haoqiang Wang, Yaxing Hao, Qiang Bai, Jianjun Hu, Yiding Li, Pengcheng Wang, Xiangyu Chen, Ran He, Bingshou Li, Xia Yang, Tingting Zhao, Yanyan Zhang, Yifei Wang, Juanjuan Ou, Houjie Liang, Yuzhang Wu, Xinyuan Zhou, Lilin Ye
Follicular regulatory T (Tfr) cells differentiate from conventional regulatory T (Treg) cells and suppress excessive germinal center (GC) responses by acting on both GC B cells and T follicular helper (Tfh) cells. Here, we examined the impact of mTOR, a serine/threonine protein kinase that senses and integrates diverse environmental cues, on the differentiation and functional competency of Tfr cells in response to protein immunization or viral infection. By genetically deleting Rptor or Rictor, essential components for mTOR complex 1 (mTORC1) and mTOR complex 2 (mTORC2), respectively, we found that mTORC1 but not mTORC2 is essential for Tfr differentiation...
September 19, 2017: Immunity
https://www.readbyqxmd.com/read/28877475/a-single-tcf-transcription-factor-regardless-of-its-activation-capacity-is-sufficient-for-effective-trilineage-differentiation-of-escs
#5
Steven Moreira, Enio Polena, Victor Gordon, Solen Abdulla, Sujeivan Mahendram, Jiayi Cao, Alexandre Blais, Geoffrey A Wood, Anna Dvorkin-Gheva, Bradley W Doble
Co-expression and cross-regulation of the four TCF/LEFs render their redundant and unique functions ambiguous. Here, we describe quadruple-knockout (QKO) mouse ESCs lacking all full-length TCF/LEFs and cell lines rescued with TCF7 or TCF7L1. QKO cells self-renew, despite gene expression patterns that differ significantly from WT, and display delayed, neurectoderm-biased, embryoid body (EB) differentiation. QKO EBs have no contracting cardiomyocytes and differentiate poorly into mesendoderm but readily generate neuronal cells...
September 5, 2017: Cell Reports
https://www.readbyqxmd.com/read/28846687/%C3%AE-catenin-is-required-for-taste-bud-cell-renewal-and-behavioral-taste-perception-in-adult-mice
#6
Dany Gaillard, Spencer G Bowles, Ernesto Salcedo, Mingang Xu, Sarah E Millar, Linda A Barlow
Taste stimuli are transduced by taste buds and transmitted to the brain via afferent gustatory fibers. Renewal of taste receptor cells from actively dividing progenitors is finely tuned to maintain taste sensitivity throughout life. We show that conditional β-catenin deletion in mouse taste progenitors leads to rapid depletion of progenitors and Shh+ precursors, which in turn causes taste bud loss, followed by loss of gustatory nerve fibers. In addition, our data suggest LEF1, TCF7 and Wnt3 are involved in a Wnt pathway regulatory feedback loop that controls taste cell renewal in the circumvallate papilla epithelium...
August 2017: PLoS Genetics
https://www.readbyqxmd.com/read/28671687/recurrent-spi1-pu-1-fusions-in-high-risk-pediatric-t-cell-acute-lymphoblastic-leukemia
#7
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...
August 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
#8
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
#9
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
#10
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...
August 2017: Stem Cells
https://www.readbyqxmd.com/read/28490440/human-memory-cd8-t-cell-effector-potential-is-epigenetically-preserved-during-in-vivo-homeostasis
#11
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
#12
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
#13
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
#14
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
#15
REVIEW
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
#16
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
#17
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
#18
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-subphenotypes-in-the-han-chinese-population
#19
L L Wen, Z W Zhu, C Yang, L Liu, X B Zuo, D L Morris, J F Dou, L Ye, Y Y Cheng, H M Guo, H Q Huang, Y Lin, C H Zhu, L L Tang, M Y Chen, Y Zhou, Y T Ding, B Liang, F S Zhou, J P Gao, X F Tang, X D Zheng, W J Wang, X Y Yin, H Y Tang, L D Sun, S Yang, X J Zhang, Y J Sheng, Y Cui
BACKGROUND: A previous study provided evidence for a genetic association between PPP2CA on 5q31.1 and systemic lupus erythematosus (SLE) across multi-ancestral cohorts, but failed to find significant evidence for an association in the Han Chinese population. OBJECTIVES: To explore the association between this locus and SLE using data from our previously published genome-wide association study (GWAS). METHODS: Single-nucleotide polymorphisms (SNPs) rs7726414 and rs244689 (near TCF7 and PPP2CA in 5q31...
September 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
#20
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
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