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PRDM1

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https://www.readbyqxmd.com/read/29760071/prdm1-silences-stem-cell-related-genes-and-inhibits-proliferation-of-human-colon-tumor-organoids
#1
Changlong Liu, Carolyn E Banister, Charles C Weige, Diego Altomare, Joseph H Richardson, Carlo M Contreras, Phillip J Buckhaults
PRDM1 is a tumor suppressor that plays an important role in B and T cell lymphomas. Our previous studies demonstrated that PRDM1β is a p53-response gene in human colorectal cancer cells. However, the function of PRDM1β in colorectal cancer cells and colon tumor organoids is not clear. Here we show that PRDM1β is a p53-response gene in human colon organoids and that low PRDM1 expression predicts poor survival in colon cancer patients. We engineered PRDM1 knockouts and overexpression clones in RKO cells and characterized the PRDM1-dependent transcript landscapes, revealing that both the α and β transcript isoforms repress MYC-response genes and stem cell-related genes...
May 14, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29720240/integrative-analysis-reveals-cd38-as-a-therapeutic-target-for-plasma-cell-rich-pre-disease-and-established-rheumatoid-arthritis-and-systemic-lupus-erythematosus
#2
Suzanne Cole, Alice Walsh, Xuefeng Yin, Mihir D Wechalekar, Malcolm D Smith, Susanna M Proudman, Douglas J Veale, Ursula Fearon, Costantino Pitzalis, Frances Humby, Michele Bombardieri, Amy Axel, Homer Adams, Christopher Chiu, Michael Sharp, John Alvarez, Ian Anderson, Loui Madakamutil, Sunil Nagpal, Yanxia Guo
BACKGROUND: Plasmablasts and plasma cells play a key role in many autoimmune diseases, such as rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). This study was undertaken to evaluate the potential of targeting CD38 as a plasma cell/plasmablast depletion mechanism by daratumumab in the treatment of patients with RA and SLE. METHODS: RNA-sequencing analysis of synovial biopsies from various stages of RA disease progression, flow cytometry analysis of peripheral blood mononuclear cells (PBMC) from patients with RA or SLE and healthy donors, immunohistochemistry assessment (IHC) of synovial biopsies from patients with early RA, and ex vivo immune cell depletion assays using daratumumab (an anti-CD38 monoclonal antibody) were used to assess CD38 as a therapeutic target...
May 2, 2018: Arthritis Research & Therapy
https://www.readbyqxmd.com/read/29713018/a-pax5-oct4-prdm1-developmental-switch-specifies-human-primordial-germ-cells
#3
Fang Fang, Benjamin Angulo, Ninuo Xia, Meena Sukhwani, Zhengyuan Wang, Charles C Carey, Aurélien Mazurie, Jun Cui, Royce Wilkinson, Blake Wiedenheft, Naoko Irie, M Azim Surani, Kyle E Orwig, Renee A Reijo Pera
Dysregulation of genetic pathways during human germ cell development leads to infertility. Here, we analysed bona fide human primordial germ cells (hPGCs) to probe the developmental genetics of human germ cell specification and differentiation. We examined the distribution of OCT4 occupancy in hPGCs relative to human embryonic stem cells (hESCs). We demonstrated that development, from pluripotent stem cells to germ cells, is driven by switching partners with OCT4 from SOX2 to PAX5 and PRDM1. Gain- and loss-of-function studies revealed that PAX5 encodes a critical regulator of hPGC development...
April 30, 2018: Nature Cell Biology
https://www.readbyqxmd.com/read/29669249/the-transcription-factor-runx3-establishes-chromatin-accessibility-of-cis-regulatory-landscapes-that-drive-memory-cytotoxic-t-lymphocyte-formation
#4
Dapeng Wang, Huitian Diao, Adam J Getzler, Walter Rogal, Megan A Frederick, Justin Milner, Bingfei Yu, Shane Crotty, Ananda W Goldrath, Matthew E Pipkin
T cell receptor (TCR) stimulation of naive CD8+ T cells initiates reprogramming of cis-regulatory landscapes that specify effector and memory cytotoxic T lymphocyte (CTL) differentiation. We mapped regions of hyper-accessible chromatin in naive cells during TCR stimulation and discovered that the transcription factor (TF) Runx3 promoted accessibility to memory CTL-specific cis-regulatory regions before the first cell division and was essential for memory CTL differentiation. Runx3 was specifically required for accessibility to regions highly enriched with IRF, bZIP and Prdm1-like TF motifs, upregulation of TFs Irf4 and Blimp1, and activation of fundamental CTL attributes in early effector and memory precursor cells...
April 17, 2018: Immunity
https://www.readbyqxmd.com/read/29528446/characterization-of-migratory-primordial-germ-cells-in-the-aorta-gonad-mesonephros-of-a-4-5-week-old-human-embryo-a-toolbox-to-evaluate-in-vitro-early-gametogenesis
#5
Maria Gomes Fernandes, Monika Bialecka, Daniela C F Salvatori, Susana M Chuva de Sousa Lopes
STUDY QUESTION: Which set of antibodies can be used to identify migratory and early post-migratory human primordial germ cells (hPGCs)? STUDY FINDING: We validated the specificity of 33 antibodies for 31 markers, including POU5F1, NANOG, PRDM1 and TFAP2C as specific markers of hPGCs at 4.5 weeks of development of Carnegie stage (CS12-13), whereas KIT and SOX17 also marked the intra-aortic hematopoietic stem cell cluster in the aorta-gonad-mesonephros (AGM). WHAT IS KNOWN ALREADY: The dynamics of gene expression during germ cell development in mice is well characterized and this knowledge has proved crucial to allow the development of protocols for the in-vitro derivation of functional gametes...
March 8, 2018: Molecular Human Reproduction
https://www.readbyqxmd.com/read/29511557/bach2-repression-mediates-th17-cell-induced-inflammation-and-associates-with-clinical-features-of-advanced-disease-in-chronic-pancreatitis
#6
M Sasikala, V V Ravikanth, K Murali Manohar, Neha Deshpande, Sandhya Singh, P Pavan Kumar, R Talukdar, Sudip Ghosh, Mohsin Aslam, G V Rao, R Pradeep, D Nageshwar Reddy
Objectives: Altered immune homeostasis and involvement of T cells has been reported in chronic pancreatitis (CP). We evaluated the role of Bach2 (BTB and CNC homology basic leucine zipper transcription factor 2), a key regulator of immune homeostasis in the chronicity of CP. Methods: Expression of Bach2 and T-cell transcription factors, enumeration of BACH2+/CD4+ T-lymphocytes were performed by qRT-PCR and flow cytometry respectively. Bach2 silenced human CD4+ T-lymphocytes were exposed to CP tissue extract to assess T-cell lineage commitment...
March 2018: United European Gastroenterology Journal
https://www.readbyqxmd.com/read/29463002/inhibitory-effect-of-purpurogallin-on-osteoclast-differentiation-in-vitro-through-the-downregulation-of-c-fos-and-nfatc1
#7
Kiryeong Kim, Tae Hoon Kim, Hye Jung Ihn, Jung Eun Kim, Je-Yong Choi, Hong-In Shin, Eui Kyun Park
Purpurogallin, a benzotropolone-containing natural compound, has been reported to exhibit numerous biological and pharmacological functions, such as antioxidant, anticancer, and anti-inflammatory effects. In this study, we enzymatically synthesized purpurogallin from pyrogallol and investigated its role in receptor activator of nuclear factor-κB ligand (RANKL)-induced osteoclastogenesis. Purpurogallin attenuated the formation of multinucleated tartrate-resistant acid phosphatase (TRAP)-positive osteoclasts from bone marrow macrophages (BMMs) without causing cytotoxicity, and suppressed upregulation of osteoclast-specific markers, including TRAP (Acp5), cathepsin K (Ctsk), and dendritic cell-specific transmembrane protein (Dcstamp)...
February 17, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29438669/trans-suppression-of-host-cdh3-and-loxl4-genes-during-cryptosporidium-parvum-infection-involves-nuclear-delivery-of-parasite-cdg7_flc_1000-rna
#8
Zhenping Ming, Ai-Yu Gong, Yang Wang, Xin-Tian Zhang, Min Li, Yao Li, Jing Pang, Stephanie Dong, Juliane K Strauss-Soukup, Xian-Ming Chen
Intestinal infection by Cryptosporidium parvum causes significant alterations in the gene expression profile in host epithelial cells. Previous studies demonstrate that a panel of parasite RNA transcripts of low protein-coding potential are delivered into infected host cells and may modulate host gene transcription. Using in vitro models of human intestinal cryptosporidiosis, we report here that trans-suppression of the cadherin 3 (CDH3) and lysyl oxidase like 4 (LOXL4) genes in human intestinal epithelial cells following C...
May 2018: International Journal for Parasitology
https://www.readbyqxmd.com/read/29426472/nuclear-delivery-of-parasite-cdg2_flc_0220-rna-transcript-to-epithelial-cells-during-cryptosporidium-parvum-infection-modulates-host-gene-transcription
#9
Guang-Hui Zhao, Ai-Yu Gong, Yang Wang, Xin-Tian Zhang, Min Li, Nicholas W Mathy, Xian-Ming Chen
Intestinal infection by the zoonotic protozoan, Cryptosporidium parvum, causes significant alterations in the gene expression profile in host epithelial cells. The molecular mechanisms of how C. parvum may modulate host cell gene transcription and the pathological significance of such alterations are largely unclear. Previous studies demonstrate that a panel of parasite RNA transcripts are delivered into infected host cells and may modulate host gene transcription. Using in vitro models of intestinal cryptosporidiosis, in this study, we analyzed the impact of host delivery of C...
February 15, 2018: Veterinary Parasitology
https://www.readbyqxmd.com/read/29416540/induction-of-short-nfatc1-%C3%AE-a-isoform-interferes-with-peripheral-b-cell-differentiation
#10
Khalid Muhammad, Ronald Rudolf, Duong Anh Thuy Pham, Stefan Klein-Hessling, Katsuyoshi Takata, Nobuko Matsushita, Volker Ellenrieder, Eisaku Kondo, Edgar Serfling
In lymphocytes, immune receptor signals induce the rapid nuclear translocation of preformed cytosolic NFAT proteins. Along with co-stimulatory signals, persistent immune receptor signals lead to high levels of NFATc1/αA, a short NFATc1 isoform, in effector lymphocytes. Whereas NFATc1 is not expressed in plasma cells, in germinal centers numerous centrocytic B cells express nuclear NFATc1/αA. When overexpressed in chicken DT40 B cells or murine WEHI 231 B cells, NFATc1/αA suppressed their cell death induced by B cell receptor signals and affected the expression of genes controlling the germinal center reaction and plasma cell formation...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29325247/-impact-of-prdm1-gene-inactivation-on-c-myc-regulation-in-diffuse-large-b-cell-lymphoma
#11
X Y Zhang, Z P Ma, W L Cui, X L Pang, R Chen, L Wang, W Zhang, X X Li
Objective: To investigate the role of PRDM1 gene inactivaion in the regulation of C-MYC in diffuse large B-cell lymphoma (DLBCL), and to explore the correlation of its immunophenotype and prognosis. Methods: 100 cases paraffin-embedded DLBCL tissues were collected from January 2009 to December 2015 at the First Affiliated Hospital of Xinjiang Medical University along with 20 cases of reactive proliferative lymph nodes as control. Immunohistochemical methods were used to detect the expression of CD20, CD10, MUM1, Ki-67, bcl-6, PRDM1/Blimp1, C-MYC and PAX5 protein...
January 8, 2018: Zhonghua Bing Li Xue za Zhi Chinese Journal of Pathology
https://www.readbyqxmd.com/read/29321612/blimp-1-prdm1-is-a-critical-regulator-of-type-iii-interferon-responses-in-mammary-epithelial-cells
#12
Salah Elias, Elizabeth J Robertson, Elizabeth K Bikoff, Arne W Mould
The transcriptional repressor Blimp-1 originally cloned as a silencer of type I interferon (IFN)-β gene expression controls cell fate decisions in multiple tissue contexts. Conditional inactivation in the mammary gland was recently shown to disrupt epithelial cell architecture. Here we report that Blimp-1 regulates expression of viral defense, IFN signaling and MHC class I pathways, and directly targets the transcriptional activator Stat1. Blimp-1 functional loss in 3D cultures of mammary epithelial cells (MECs) results in accumulation of dsRNA and expression of type III IFN-λ...
January 10, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29291257/aire-a-missing-link-to-explain-female-susceptibility-to-autoimmune-diseases
#13
REVIEW
Sonia Berrih-Aknin, Rozen Le Panse, Nadine Dragin
Women are more susceptible to autoimmune diseases than men. Autoimmunity results from tolerance breakdown toward self-components. Recently, three transcription modulators were identified in medullary thymic epithelial cells that orchestrate immune central tolerance processes: the autoimmune regulator (AIRE), FEZ family zinc finger 2 (FEZF2 or FEZ1), and PR domain zinc finger protein 1 (PRDM1). Interestingly, these three transcription modulators regulate nonredundant tissue-specific antigen subsets and thus cover broad antigen diversity...
January 2018: Annals of the New York Academy of Sciences
https://www.readbyqxmd.com/read/29242551/ezh2-phosphorylation-state-determines-its-capacity-to-maintain-cd8-t-memory-precursors-for-antitumor-immunity
#14
Shan He, Yongnian Liu, Lijun Meng, Hongxing Sun, Ying Wang, Yun Ji, Janaki Purushe, Pan Chen, Changhong Li, Jozef Madzo, Jean-Pierre Issa, Jonathan Soboloff, Ran Reshef, Bethany Moore, Luca Gattinoni, Yi Zhang
Memory T cells sustain effector T-cell production while self-renewing in reaction to persistent antigen; yet, excessive expansion reduces memory potential and impairs antitumor immunity. Epigenetic mechanisms are thought to be important for balancing effector and memory differentiation; however, the epigenetic regulator(s) underpinning this process remains unknown. Herein, we show that the histone methyltransferase Ezh2 controls CD8+ T memory precursor formation and antitumor activity. Ezh2 activates Id3 while silencing Id2, Prdm1 and Eomes, promoting the expansion of memory precursor cells and their differentiation into functional memory cells...
December 14, 2017: Nature Communications
https://www.readbyqxmd.com/read/29222434/embryonic-lethality-and-defective-male-germ-cell-development-in-mice-lacking-utf1
#15
Seth D Kasowitz, Mengcheng Luo, Jun Ma, N Adrian Leu, P Jeremy Wang
The germ cell lineage is specified early in embryogenesis and undergoes complex developmental programs to generate gametes. Here, we conducted genetic studies to investigate the role of Utf1 (Undifferentiated embryonic cell transcription factor 1) in mouse germ cell development. Utf1 is expressed in pluripotent embryonic stem (ES) cells and regulates ES cell differentiation. In a proteomics screen, we identified UTF1 among 38 proteins including DNMT3L and DND1 that associate with chromatin in embryonic testes...
December 8, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29209042/analysis-of-the-genomic-landscape-of-multiple-myeloma-highlights-novel-prognostic-markers-and-disease-subgroups
#16
N Bolli, G Biancon, M Moarii, S Gimondi, Y Li, C de Philippis, F Maura, V Sathiaseelan, Y-T Tai, L Mudie, S O'Meara, K Raine, J W Teague, A P Butler, C Carniti, M Gerstung, T Bagratuni, E Kastritis, M Dimopoulos, P Corradini, K Anderson, P Moreau, S Minvielle, P J Campbell, E Papaemmanuil, H Avet-Loiseau, N C Munshi
In multiple myeloma, next generation sequencing (NGS) has expanded our knowledge of genomic lesions, and highlighted a dynamic and heterogeneous composition of the tumor. Here, we used NGS to characterize the genomic landscape of 418 multiple myeloma cases at diagnosis and correlate this with prognosis and classification. Translocations and copy number changes (CNAs) had a preponderant contribution over gene mutations in defining the genotype and prognosis of each case. Known and novel independent prognostic markers were identified in our cohort of proteasome inhibitor and IMiD-treated patients with long follow-up, including events with context-specific prognostic value, such as deletions of the PRDM1 gene...
December 6, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/29158490/long-lived-unipotent-blimp1-positive-luminal-stem-cells-drive-mammary-gland-organogenesis-throughout-adult-life
#17
Salah Elias, Marc A Morgan, Elizabeth K Bikoff, Elizabeth J Robertson
The hierarchical relationships between various stem and progenitor cell subpopulations driving mammary gland morphogenesis and homoeostasis are poorly understood. Conditional inactivation experiments previously demonstrated that expression of the zinc finger transcriptional repressor Blimp1/PRDM1 is essential for the establishment of epithelial cell polarity and functional maturation of alveolar cells. Here we exploit a Prdm1.CreERT2-LacZ reporter allele for lineage tracing experiments. Blimp1 expression marks a rare subpopulation of unipotent luminal stem cells that initially appear in the embryonic mammary gland at around E17...
November 20, 2017: Nature Communications
https://www.readbyqxmd.com/read/29029226/new-insights-into-the-genetic-basis-of-monge-s-disease-and-adaptation-to-high-altitude
#18
Tsering Stobdan, Ali Akbari, Priti Azad, Dan Zhou, Orit Poulsen, Otto Appenzeller, Gustavo F Gonzales, Amalio Telenti, Emily H M Wong, Shubham Saini, Ewen F Kirkness, J Craig Venter, Vineet Bafna, Gabriel G Haddad
Human high-altitude (HA) adaptation or mal-adaptation is explored to understand the physiology, pathophysiology, and molecular mechanisms that underlie long-term exposure to hypoxia. Here, we report the results of an analysis of the largest whole-genome-sequencing of Chronic Mountain Sickness (CMS) and nonCMS individuals, identified candidate genes and functionally validated these candidates in a genetic model system (Drosophila). We used PreCIOSS algorithm that uses Haplotype Allele Frequency score to separate haplotypes carrying the favored allele from the noncarriers and accordingly, prioritize genes associated with the CMS or nonCMS phenotype...
December 1, 2017: Molecular Biology and Evolution
https://www.readbyqxmd.com/read/28983055/pattern-of-somatic-mutations-in-patients-with-waldenstr%C3%A3-m-macroglobulinemia-or-igm-monoclonal-gammopathy-of-undetermined-significance
#19
Marzia Varettoni, Silvia Zibellini, Irene Defrancesco, Virginia Valeria Ferretti, Ettore Rizzo, Luca Malcovati, Anna Gallì, Matteo Giovanni Della Porta, Emanuela Boveri, Luca Arcaini, Chiara Candido, Marco Paulli, Mario Cazzola
We analyzed MYD88 and CXCR4 mutation status of 260 patients with Waldenström macroglobulinemia or IgM monoclonal gammopathy of undetermined significance using allele-specific real time quantitative polymerase chain reaction and Sanger sequencing, respectively. A subgroup of 119 patients was further studied with next-generation sequencing of 11 target genes ( MYD88 , CXCR4 , ARID1A , KMT2D , NOTCH2 , TP53 , PRDM1 , CD79B , TRAF3 , MYBBP1A , and TNFAIP3 ). MYD88 (L265P) was found at diagnosis in 91% of patients with Waldenström macroglobulinemia and in 60% of patients with IgM monoclonal gammopathy of undetermined significance using allele-specific polymerase chain reaction analysis...
December 2017: Haematologica
https://www.readbyqxmd.com/read/28977998/nkl-homeobox-gene-msx1-acts-like-a-tumor-suppressor-in-nk-cell-leukemia
#20
Stefan Nagel, Claudia Pommerenke, Corinna Meyer, Maren Kaufmann, Roderick A F MacLeod, Hans G Drexler
NKL homeobox gene MSX1 is physiologically expressed in lymphoid progenitors and subsequently downregulated in developing T- and B-cells. In contrast, elevated expression levels of MSX1 persist in mature natural killer (NK)-cells, indicating a functional role in this compartment. While T-cell acute lymphoblastic leukemia (T-ALL) subsets exhibit aberrant overexpression of MSX1, we show here that in malignant NK-cells the level of MSX1 transcripts is aberrantly downregulated. Chromosomal deletions at 4p16 hosting the MSX1 locus have been described in NK-cell leukemia patients...
September 15, 2017: Oncotarget
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