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Blimp1

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https://www.readbyqxmd.com/read/29158490/long-lived-unipotent-blimp1-positive-luminal-stem-cells-drive-mammary-gland-organogenesis-throughout-adult-life
#1
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/29141218/reciprocal-expression-of-il-35-and-il-10-defines-two-distinct-effector-treg-subsets-that-are-required-for-maintenance-of-immune-tolerance
#2
Xundong Wei, Jianhua Zhang, Qianchong Gu, Man Huang, Wei Zhang, Jie Guo, Xuyu Zhou
Regulatory T cells (Tregs) can exert their functions through multiple suppressive mechanisms; however, it is unclear how Tregs exactly employ these mechanisms. In this study, we found that interleukin-35 (IL-35)-producing Tregs were a distinct effector population from the IL-10-producing subset. We also revealed that these two subsets of effector Tregs have different transcription factor dependency. Terminal differentiation regulator Blimp1 was only critical for IL-10 production, but not for IL-35; Foxp3 was essential for IL-35 but dispensable for IL-10 production...
November 14, 2017: Cell Reports
https://www.readbyqxmd.com/read/29138422/fam19a5-a-brain-specific-chemokine-inhibits-rankl-induced-osteoclast-formation-through-formyl-peptide-receptor-2
#3
Min Young Park, Hyung Sik Kim, Mingyu Lee, Byunghyun Park, Ha Young Lee, Eun Bee Cho, Jae Young Seong, Yoe-Sik Bae
Osteoclasts can be differentiated from bone marrow-derived macrophages (BMDM). They play a key role in bone resorption. Identifying novel molecules that can regulate osteoclastogenesis has been an important issue. In this study, we found that FAM19A5, a neurokine or brain-specific chemokine, strongly stimulated mouse BMDM, resulting in chemotactic migration and inhibition of RANKL-induced osteoclastogenesis. Expression levels of osteoclast-related genes such as RANK, TRAF6, OSCAR, TRAP, Blimp1, c-fos, and NFATc1 were markedly decreased by FAM19A5...
November 14, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29070123/-effect-of-b-lymphocyte-induced-mature-protein-1-expression-in-bone-marrow-mononuclear-cells-on-prognosis-of-patients-with-multiple-myeloma
#4
Guo-Sheng Liu, Jiao-Ping Wang, Zhi-Hua Chu, Ying-Ying Yu, Wei Zhou
OBJECTIVE: To study the effect of B lymphocyte-induced mature protein-1(Blimp1) expression in bone marrow mononuclear cells on the prognosis of patients with multiple myeloma. METHODS: Forty-eight patients with multiple myeloma from January 2014 to January 2015 were selected. The expression of Blimp1 in the bone marrow of all the patients was measured. According to the median score of Blimp1 expression level, the patients was divided into low expression group (L group, 22 cases) and high expression group (H group, 26 cases)...
October 2017: Zhongguo Shi Yan Xue Ye Xue za Zhi
https://www.readbyqxmd.com/read/28985527/evolutionarily-distinctive-transcriptional-and-signaling-programs-drive-human-germ-cell-lineage-specification-from-pluripotent-stem-cells
#5
Yoji Kojima, Kotaro Sasaki, Shihori Yokobayashi, Yoshitake Sakai, Tomonori Nakamura, Yukihiro Yabuta, Fumio Nakaki, So Nagaoka, Knut Woltjen, Akitsu Hotta, Takuya Yamamoto, Mitinori Saitou
Germline specification underlies human reproduction and evolution, but it has proven difficult to study in humans since it occurs shortly after blastocyst implantation. This process can be modeled with human induced pluripotent stem cells (hiPSCs) by differentiating them into primordial germ cell-like cells (hPGCLCs) through an incipient mesoderm-like cell (iMeLC) state. Here, we elucidate the key transcription factors and their interactions with important signaling pathways in driving hPGCLC differentiation from iPSCs...
October 5, 2017: Cell Stem Cell
https://www.readbyqxmd.com/read/28981894/principles-for-the-regulation-of-multiple-developmental-pathways-by-a-versatile-transcriptional-factor-blimp1
#6
Tadahiro Mitani, Yukihiro Yabuta, Hiroshi Ohta, Tomonori Nakamura, Chika Yamashiro, Takuya Yamamoto, Mitinori Saitou, Kazuki Kurimoto
Single transcription factors (TFs) regulate multiple developmental pathways, but the underlying mechanisms remain unclear. Here, we quantitatively characterized the genome-wide occupancy profiles of BLIMP1, a key transcriptional regulator for diverse developmental processes, during the development of three germ-layer derivatives (photoreceptor precursors, embryonic intestinal epithelium and plasmablasts) and the germ cell lineage (primordial germ cells). We identified BLIMP1-binding sites shared among multiple developmental processes, and such sites were highly occupied by BLIMP1 with a stringent recognition motif and were located predominantly in promoter proximities...
September 11, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28969006/the-molecular-characterization-of-porcine-egg-precursor-cells
#7
Te-Sha Tsai, Jacqueline Johnson, Yvonne White, Justin C John
Female-factor infertility can be caused by poor oocyte quality and depleted ovarian reserves. Egg precursor cells (EPCs), isolated from the ovarian cortex, have the potential to be used to overcome female infertility. We aimed to define the origins of EPCs by analyzing their gene expression profiles and mtDNA content using a mini-pig model. We characterized FAC-sorted DDX4(+)-derived porcine EPCs by performing RNA-sequencing and determined that they utilize pathways important for cell cycle and proliferation, which supports the existence of adult mitotically active oogonial cells...
September 8, 2017: Oncotarget
https://www.readbyqxmd.com/read/28955330/perturbation-of-b-cell-gene-expression-persists-in-hiv-infected-children-despite-effective-antiretroviral-therapy-and-predicts-h1n1-response
#8
Nicola Cotugno, Lesley De Armas, Suresh Pallikkuth, Stefano Rinaldi, Biju Issac, Alberto Cagigi, Paolo Rossi, Paolo Palma, Savita Pahwa
Despite effective antiretroviral therapy (ART), HIV-infected individuals with apparently similar clinical and immunological characteristics can vary in responsiveness to vaccinations. However, molecular mechanisms responsible for such impairment, as well as biomarkers able to predict vaccine responsiveness in HIV-infected children, remain unknown. Following the hypothesis that a B cell qualitative impairment persists in HIV-infected children (HIV) despite effective ART and phenotypic B cell immune reconstitution, the aim of the current study was to investigate B cell gene expression of HIV compared to age-matched healthy controls (HCs) and to determine whether distinct gene expression patterns could predict the ability to respond to influenza vaccine...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28935958/differential-regulation-of-effector-and-regulatory-t-cell-function-by-blimp1
#9
Rashmi Bankoti, Chihiro Ogawa, Truc Nguyen, Lena Emadi, Michael Couse, Soofia Salehi, Xuemo Fan, Deepti Dhall, Yizhou Wang, Jordan Brown, Vincent Funari, Jie Tang, Gislâine A Martins
The transcriptional regulator Blimp1 plays crucial roles in controlling terminal differentiation in several lineages. In T cells, Blimp1 is expressed in both effector (Teff) and regulatory (Treg) cells, and mice with T cell-specific deletion of Blimp1 (Blimp1CKO mice) spontaneously develop severe intestinal inflammation, indicating a crucial role for Blimp1 in T cell homeostasis regulation. Blimp1 has been shown to function as a direct activator of the Il10 gene and although its requirement for IL10 expression has been demonstrated in both Treg and Teff cells under inflammatory conditions, the intrinsic requirement of Blimp1 for homeostatic maintenance of these T cell subsets had not been investigated...
September 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28878266/transglutaminase-2-regulates-osteoclast-differentiation-via-a-blimp1-dependent-pathway
#10
Woo-Shin Kim, Haemin Kim, Eui Man Jeong, Hyung Joon Kim, Zang Hee Lee, In-Gyu Kim, Hong-Hee Kim
Transglutaminase 2 (TG2) performs multiple reactions, including transamidation, and also plays a role in signal transduction as a GTP-binding protein. In this study, we reveal that TG2 controls osteoclast differentiation and bone homeostasis in mice. Osteoclasts specifically expressed the TG2 isoform among eight TG family members. Suppression in TG2 expression with siRNA led to increased osteoclast formation from primary mouse precursor cells in response to receptor activator of nuclear factor kappaB ligand (RANKL)...
September 6, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28875978/il4-and-il21-cooperate-to-induce-the-high-bcl6-protein-level-required-for-germinal-center-formation
#11
Stéphane Chevrier, Tobias Kratina, Dianne Emslie, David M Tarlinton, Lynn M Corcoran
Bcl6 (B-cell lymphoma 6) is a transcriptional repressor and critical mediator of the germinal center reaction during a T-cell-dependent antibody response, where it enables somatic hypermutation of immunoglobulin genes and inhibits terminal differentiation via repression of Blimp1. It can also contribute to the development of diffuse large B-cell lymphoma when expressed inappropriately. Bcl6 regulation is mediated both at the transcriptional and post-transcriptional levels, and in particular a strong signal through the B-cell receptor causes rapid proteasomal degradation of Bcl6...
October 3, 2017: Immunology and Cell Biology
https://www.readbyqxmd.com/read/28851699/an-aberrant-notch2-bcr-signaling-axis-in-b-cells-from-patients-with-chronic-gvhd
#12
Jonathan C Poe, Wei Jia, Hsuan Su, Sarah Anand, Jeremy J Rose, Prasanthi V Tata, Amy N Suthers, Corbin D Jones, Pei Fen Kuan, Benjamin G Vincent, Jonathan S Serody, Mitchell E Horwitz, Vincent T Ho, Steven Z Pavletic, Frances T Hakim, Kouros Owzar, Dadong Zhang, Bruce R Blazar, Christian W Siebel, Nelson J Chao, Ivan Maillard, Stefanie Sarantopoulos
B Cell Receptor (BCR)-activated B cells contribute to pathogenesis in chronic graft-versus-host disease (cGVHD), a condition manifested by both B cell autoreactivity and immune deficiency. We hypothesized that constitutive BCR activation precluded functional B cell maturation in cGVHD. To address this, we examined BCR-NOTCH2 synergy, since Notch has been shown to increase BCR responsiveness in normal mouse B cells. We conducted ex vivo activation and signaling assays of 30 primary samples from HCT patients with and without cGVHD...
August 29, 2017: Blood
https://www.readbyqxmd.com/read/28835384/ezh2-inhibition-by-tazemetostat-results-in-altered-dependency-on-b-cell-activation-signaling-in-dlbcl
#13
Dorothy Brach, Danielle Johnston-Blackwell, Allison Drew, Trupti Lingaraj, Vinny Motwani, Natalie M Warholic, Igor Feldman, Christopher Plescia, Jesse J Smith, Robert A Copeland, Heike Keilhack, Elayne Chan-Penebre, Sarah K Knutson, Scott A Ribich, Alejandra Raimondi, Michael J Thomenius
The EZH2 small-molecule inhibitor tazemetostat (EPZ-6438) is currently being evaluated in phase II clinical trials for the treatment of non-Hodgkin lymphoma (NHL). We have previously shown that EZH2 inhibitors display an antiproliferative effect in multiple preclinical models of NHL, and that models bearing gain-of-function mutations in EZH2 were consistently more sensitive to EZH2 inhibition than lymphomas with wild-type (WT) EZH2 Here, we demonstrate that cell lines bearing EZH2 mutations show a cytotoxic response, while cell lines with WT-EZH2 show a cytostatic response and only tumor growth inhibition without regression in a xenograft model...
November 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/28833081/transcriptional-repressor-blimp1-regulates-follicular-regulatory-t-cell-homeostasis-and-function
#14
Guang Yang, Xiaosu Yang, Junmei Zhang, Guancheng Li, Dandan Zheng, Anjiao Peng, Jue Hu, Liqun Xu, Baifeng Yang, Huan Yang, Wenbin Zhou, Erdem Tuzun, Jing Li
The B-lymphocyte-induced maturation protein 1 (Blimp1) regulates T-cell homeostasis and function. Loss of Blimp1 could double the proportion of follicular regulatory T (Tfr) cells. However, the effects that Blimp1 may have on the function of Tfr cells remain unknown. Here we document the function for Blimp1 in Tfr cells in vitro and in vivo. Data presented in this study demonstrate that Tfr cells indirectly inhibit the activation and differentiation of B cells by negatively regulating follicular helper T cells, so lowering the secretion of antibody...
August 20, 2017: Immunology
https://www.readbyqxmd.com/read/28829770/combinatorial-regulation-of-a-blimp1-prdm1-enhancer-in-the-mouse-retina
#15
Taylor S Mills, Tatiana Eliseeva, Stephanie M Bersie, Grace Randazzo, Jhenya Nahreini, Ko Uoon Park, Joseph A Brzezinski
The mouse retina comprises seven major cell types that exist in differing proportions. They are generated from multipotent progenitors in a stochastic manner, such that the relative frequency of any given type generated changes over time. The mechanisms determining the proportions of each cell type are only partially understood. Photoreceptors and bipolar interneurons are derived from cells that express Otx2. Within this population, Blimp1 (Prdm1) helps set the balance between photoreceptors and bipolar cells by suppressing bipolar identity in most of the cells...
2017: PloS One
https://www.readbyqxmd.com/read/28790031/blimp1-induces-transient-metastatic-heterogeneity-in-pancreatic-cancer
#16
Shin-Heng Chiou, Viviana I Risca, Gordon X Wang, Dian Yang, Barbara M Grüner, Arwa S Kathiria, Rosanna K Ma, Dedeepya Vaka, Pauline Chu, Margaret Kozak, Laura Castellini, Edward E Graves, Grace E Kim, Philippe Mourrain, Albert C Koong, Amato J Giaccia, Monte M Winslow
Pancreatic ductal adenocarcinoma (PDAC) is one of the most metastatic and deadly cancers. Despite the clinical significance of metastatic spread, our understanding of molecular mechanisms that drive PDAC metastatic ability remains limited. By generating a genetically engineered mouse model of human PDAC, we uncover a transient subpopulation of cancer cells with exceptionally high metastatic ability. Global gene expression profiling and functional analyses uncovered the transcription factor BLIMP1 as a driver of PDAC metastasis...
October 2017: Cancer Discovery
https://www.readbyqxmd.com/read/28768724/pd-l2-regulates-b-1-cell-antibody-production-against-phosphorylcholine-through-an-il-5-dependent-mechanism
#17
Jerome T McKay, Marcela A Haro, Christina A Daly, Rama D Yammani, Bing Pang, W Edward Swords, Karen M Haas
B-1 cells produce natural Abs which provide an integral first line of defense against pathogens while also performing important homeostatic housekeeping functions. In this study, we demonstrate that programmed cell death 1 ligand 2 (PD-L2) regulates the production of natural Abs against phosphorylcholine (PC). Naive PD-L2-deficient (PD-L2(-/-)) mice produced significantly more PC-reactive IgM and IgA. This afforded PD-L2(-/-) mice with selectively enhanced protection against PC-expressing nontypeable Haemophilus influenzae, but not PC-negative nontypeable Haemophilus influenzae, relative to wild-type mice...
September 15, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28758191/interleukin-27-signalling-induces-stem-cell-antigen-1-expression-in-t-lymphocytes-in%C3%A2-vivo
#18
Zhihao Liu, Lisha Wu, Jing Zhu, Xiaotong Zhu, Jianmin Zhu, Jin-Qing Liu, Jianchao Zhang, Jonathan P Davis, Sanjay Varikuti, Abhay R Satoskar, Jie Zhou, Ming-Song Li, Xue-Feng Bai
Stem cell antigen-1 (Sca-1/Ly6A/E) is a cell surface glycoprotein that is often used as a biomarker for stem cells and cell stemness. However, it is not clear what factors can directly induce the expression of Sca-1/Ly6A/E in T lymphocytes in vivo, and if induction of Sca-1 is associated with T cell stemness. In this study, we show that interleukin-27 (IL-27), a member of the IL-12 family of cytokines, directly induces Sca-1 expression in T cells in vivo. We found that mice-deficient for IL-27 (either P28 or EBI3) or its signalling (IL-27Rα) had profound reduction of Sca-1 expression in naive (CD62L(+)  CD44(-) ), memory (CD62L(+)  CD44(+) ) and effector (CD62L(-)  CD44(+) ) T cells...
December 2017: Immunology
https://www.readbyqxmd.com/read/28757909/metabolic-reprogramming-autophagy-and-reactive-oxygen-species-are-necessary-for-primordial-germ-cell-reprogramming-into-pluripotency
#19
D Sainz de la Maza, A Moratilla, V Aparicio, C Lorca, Y Alcaina, D Martín, M P De Miguel
Cellular reprogramming is accompanied by a metabolic shift from oxidative phosphorylation (OXPHOS) toward glycolysis. Previous results from our laboratory showed that hypoxia alone is able to reprogram primordial germ cells (PGCs) into pluripotency and that this action is mediated by hypoxia-inducible factor 1 (HIF1). As HIF1 exerts a myriad of actions by upregulating several hundred genes, to ascertain whether the metabolic switch toward glycolysis is solely responsible for reprogramming, PGCs were cultured in the presence of a pyruvate kinase M2 isoform (PKM2) activator, or glycolysis was promoted by manipulating PPARγ...
2017: Oxidative Medicine and Cellular Longevity
https://www.readbyqxmd.com/read/28754907/mapping-the-chromatin-landscape-and-blimp1-transcriptional-targets-that-regulate-trophoblast-differentiation
#20
Andrew C Nelson, Arne W Mould, Elizabeth K Bikoff, Elizabeth J Robertson
Trophoblast stem cells (TSCs) give rise to specialized cell types within the placenta. However, the regulatory mechanisms that guide trophoblast cell fate decisions during placenta development remain ill defined. Here we exploited ATAC-seq and transcriptional profiling strategies to describe dynamic changes in gene expression and chromatin accessibility during TSC differentiation. We detect significantly increased chromatin accessibility at key genes upregulated as TSCs exit from the stem cell state. However, downregulated gene expression is not simply due to the loss of chromatin accessibility in proximal regions...
July 28, 2017: Scientific Reports
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