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  • 1
    Abstract: The impact of epigenetics on the differentiation of memory T (Tmem) cells is poorly defined. We generated deep epigenomes comprising genome-wide profiles of DNA methylation, histone modifications, DNA accessibility, and coding and non-coding RNA expression in naive, central-, effector-, and terminally differentiated CD45RA+ CD4+ Tmem cells from blood and CD69+ Tmem cells from bone marrow (BM-Tmem). We observed a progressive and proliferation-associated global loss of DNA methylation in heterochromatic parts of the genome during Tmem cell differentiation. Furthermore, distinct gradually changing signatures in the epigenome and the transcriptome supported a linear model of memory development in circulating T cells, while tissue-resident BM-Tmem branched off with a unique epigenetic profile. Integrative analyses identified candidate master regulators of Tmem cell differentiation, including the transcription factor FOXP1. This study highlights the importance of epigenomic changes for Tmem cell biology and demonstrates the value of epigenetic data for the identification of lineage regulators.
    Type of Publication: Journal article published
    PubMed ID: 27851915
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  • 2
    Abstract: Recent studies have shown that tissue macrophages (MPhi) arise from embryonic progenitors of the yolk sac (YS) and fetal liver and colonize tissues before birth. Further studies have proposed that developmentally distinct tissue MPhi can be identified based on the differential expression of F4/80 and CD11b, but whether a characteristic transcriptional profile exists is largely unknown. Here, we took advantage of an inducible fate-mapping system that facilitated the identification of CD45(+)c-kit(-)CX3CR1(+)F4/80(+) (A2) progenitors of the YS as the source of F4/80(hi) but not CD11b(hi) MPhi. Large-scale transcriptional profiling of MPhi precursors from the YS stage to adulthood allowed for building computational models for F4/80(hi) tissue macrophages being direct descendants of A2 progenitors. We further identified a distinct molecular signature of F4/80(hi) and CD11b(hi) MPhi and found that Irf8 was vital for MPhi maturation. Our data provide new cellular and molecular insights into the origin and developmental pathways of tissue MPhi.
    Type of Publication: Journal article published
    PubMed ID: 27412700
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  • 3
  • 4
    Publication Date: 2018-12-21
    Description: Forkhead box class O1 (FOXO1) acts as a tumor suppressor in solid tumors. The oncogenic phosphoinositide-3-kinase (PI3K) pathway suppresses FOXO1 transcriptional activity by enforcing its nuclear exclusion upon AKT-mediated phosphorylation. We show here abundant nuclear expression of FOXO1 in Burkitt lymphoma (BL), a germinal center (GC) B-cell–derived lymphoma whose pathogenesis is linked to PI3K activation. Recurrent FOXO1 mutations, which prevent AKT targeting and lock the transcription factor in the nucleus, are used by BL to circumvent mutual exclusivity between PI3K and FOXO1 activation. Using genome editing in human and mouse lymphomas in which MYC and PI3K cooperate synergistically in tumor development, we demonstrate proproliferative and antiapoptotic activity of FOXO1 in BL and identify its nuclear localization as an oncogenic event in GC B-cell–derived lymphomagenesis.
    Keywords: Lymphoid Neoplasia
    Print ISSN: 0006-4971
    Electronic ISSN: 1528-0020
    Topics: Biology , Medicine
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  • 5
    Publication Date: 2015-10-31
    Description: Antitumor immunity driven by intratumoral dendritic cells contributes to the efficacy of anthracycline-based chemotherapy in cancer. We identified a loss-of-function allele of the gene coding for formyl peptide receptor 1 (FPR1) that was associated with poor metastasis-free and overall survival in breast and colorectal cancer patients receiving adjuvant chemotherapy. The therapeutic effects of anthracyclines were abrogated in tumor-bearing Fpr1(-/-) mice due to impaired antitumor immunity. Fpr1-deficient dendritic cells failed to approach dying cancer cells and, as a result, could not elicit antitumor T cell immunity. Experiments performed in a microfluidic device confirmed that FPR1 and its ligand, annexin-1, promoted stable interactions between dying cancer cells and human or murine leukocytes. Altogether, these results highlight the importance of FPR1 in chemotherapy-induced anticancer immune responses.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Vacchelli, Erika -- Ma, Yuting -- Baracco, Elisa E -- Sistigu, Antonella -- Enot, David P -- Pietrocola, Federico -- Yang, Heng -- Adjemian, Sandy -- Chaba, Kariman -- Semeraro, Michaela -- Signore, Michele -- De Ninno, Adele -- Lucarini, Valeria -- Peschiaroli, Francesca -- Businaro, Luca -- Gerardino, Annamaria -- Manic, Gwenola -- Ulas, Thomas -- Gunther, Patrick -- Schultze, Joachim L -- Kepp, Oliver -- Stoll, Gautier -- Lefebvre, Celine -- Mulot, Claire -- Castoldi, Francesca -- Rusakiewicz, Sylvie -- Ladoire, Sylvain -- Apetoh, Lionel -- Bravo-San Pedro, Jose Manuel -- Lucattelli, Monica -- Delarasse, Cecile -- Boige, Valerie -- Ducreux, Michel -- Delaloge, Suzette -- Borg, Christophe -- Andre, Fabrice -- Schiavoni, Giovanna -- Vitale, Ilio -- Laurent-Puig, Pierre -- Mattei, Fabrizio -- Zitvogel, Laurence -- Kroemer, Guido -- New York, N.Y. -- Science. 2015 Nov 20;350(6263):972-8. doi: 10.1126/science.aad0779. Epub 2015 Oct 29.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Gustave Roussy Cancer Campus, Villejuif, France. INSERM, U1138, Paris, France. Equipe 11 Labellisee par la Ligue Nationale Contre le Cancer, Centre de Recherche des Cordeliers, Paris, France. Universite Paris Descartes, Sorbonne Paris Cite, Paris, France. Universite Pierre et Marie Curie, Paris, France. ; Gustave Roussy Cancer Campus, Villejuif, France. INSERM, U1138, Paris, France. Equipe 11 Labellisee par la Ligue Nationale Contre le Cancer, Centre de Recherche des Cordeliers, Paris, France. Universite Paris Descartes, Sorbonne Paris Cite, Paris, France. Universite Pierre et Marie Curie, Paris, France. Suzhou Institute of Systems Medicine, Suzhou, Jiangsu, China. Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China. ; Gustave Roussy Cancer Campus, Villejuif, France. INSERM, U1138, Paris, France. Equipe 11 Labellisee par la Ligue Nationale Contre le Cancer, Centre de Recherche des Cordeliers, Paris, France. Faculte de Medecine, Universite Paris-Saclay, Kremlin-Bicetre, France. ; Regina Elena National Cancer Institute, Rome, Italy. ; Gustave Roussy Cancer Campus, Villejuif, France. INSERM, U1138, Paris, France. Equipe 11 Labellisee par la Ligue Nationale Contre le Cancer, Centre de Recherche des Cordeliers, Paris, France. Metabolomics and Cell Biology Platforms, Gustave Roussy Cancer Campus, Villejuif, France. ; Gustave Roussy Cancer Campus, Villejuif, France. INSERM, U1138, Paris, France. Equipe 11 Labellisee par la Ligue Nationale Contre le Cancer, Centre de Recherche des Cordeliers, Paris, France. ; Gustave Roussy Cancer Campus, Villejuif, France. INSERM, U1138, Paris, France. Equipe 11 Labellisee par la Ligue Nationale Contre le Cancer, Centre de Recherche des Cordeliers, Paris, France. Universite Paris Descartes, Sorbonne Paris Cite, Paris, France. ; Gustave Roussy Cancer Campus, Villejuif, France. INSERM, U1015, Villejuif, France. Center of Clinical Investigations in Biotherapies of Cancer (CICBT) 507, Villejuif, France. ; Department of Hematology, Oncology, and Molecular Medicine, Istituto Superiore di Sanita, Rome, Italy. ; Italian National Research Council, Institute for Photonics and Nanotechnology, Rome, Italy. ; Genomics and Immunoregulation, Life and Medical Science Center Institute, University of Bonn, Germany. ; Gustave Roussy Cancer Campus, Villejuif, France. INSERM, U981, Villejuif, France. ; Universite Paris Sorbonne Cite, UMRS 775, INSERM, Paris, France. INSERM U1147, Centre de Ressources Biologiques (CRB) EPIGENETIC, Paris, France. ; Gustave Roussy Cancer Campus, Villejuif, France. INSERM, U1138, Paris, France. Equipe 11 Labellisee par la Ligue Nationale Contre le Cancer, Centre de Recherche des Cordeliers, Paris, France. Faculte de Medecine, Universite Paris-Saclay, Kremlin-Bicetre, France. Sotio, Prague, Czech Republic. ; Department of Medical Oncology, Centre Georges-Francois Leclerc, Dijon, France. Universite Bourgogne Franche-Comte, Dijon, France. Centre Georges Francois Leclerc, Dijon, France. ; Department of Life Sciences, University of Siena, Siena, Italy. ; Institut du Cerveau et de la Moelle Epiniere, ICM CNRS UMR 7225 - INSERM U 1127 - UPMC-P6 UMR S 1127, Equipe Neurogenetique et Physiologie Hopital de la Pitie-Salpetriere, 47, Boulevard de l'Hopital, 75013 Paris, France. ; INSERM U1147, Centre de Ressources Biologiques (CRB) EPIGENETIC, Paris, France. Department of Medical Oncology, Gustave Roussy Cancer Campus, Villejuif Cedex, France. ; Faculte de Medecine, Universite Paris-Saclay, Kremlin-Bicetre, France. Department of Medical Oncology, Gustave Roussy Cancer Campus, Villejuif Cedex, France. ; INSERM, U981, Villejuif, France. Department of Breast Oncology, Gustave Roussy Cancer Campus, Villejuif, France. ; University of Franche-Comte, INSERM 1098, France. ; Gustave Roussy Cancer Campus, Villejuif, France. INSERM, U981, Villejuif, France. Department of Biology and Pathology, Gustave Roussy Cancer Campus, Villejuif, France. Department of Medical Oncology, Gustave Roussy Cancer Campus, Villejuif, France. ; Regina Elena National Cancer Institute, Rome, Italy. Department of Biology, University of Rome "Tor Vergata," Rome, Italy. ; Universite Paris Sorbonne Cite, UMRS 775, INSERM, Paris, France. INSERM U1147, Centre de Ressources Biologiques (CRB) EPIGENETIC, Paris, France. Pole de Biologie, Hopital Europeen Georges Pompidou, AP-HP, Paris, France. ; Gustave Roussy Cancer Campus, Villejuif, France. Faculte de Medecine, Universite Paris-Saclay, Kremlin-Bicetre, France. INSERM, U1015, Villejuif, France. Center of Clinical Investigations in Biotherapies of Cancer (CICBT) 507, Villejuif, France. kroemer@orange.fr laurence.zitvogel@gustaveroussy.fr. ; Gustave Roussy Cancer Campus, Villejuif, France. INSERM, U1138, Paris, France. Equipe 11 Labellisee par la Ligue Nationale Contre le Cancer, Centre de Recherche des Cordeliers, Paris, France. Universite Paris Descartes, Sorbonne Paris Cite, Paris, France. Universite Pierre et Marie Curie, Paris, France. Metabolomics and Cell Biology Platforms, Gustave Roussy Cancer Campus, Villejuif, France. Pole de Biologie, Hopital Europeen Georges Pompidou, AP-HP, Paris, France. Karolinska Institute, Department of Women's and Children's Health, Karolinska University Hospital, 17176 Stockholm, Sweden. kroemer@orange.fr laurence.zitvogel@gustaveroussy.fr.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26516201" target="_blank"〉PubMed〈/a〉
    Keywords: Alleles ; Animals ; Annexin A1/metabolism/pharmacology ; Anthracyclines/*therapeutic use ; Breast Neoplasms/drug therapy/immunology ; Cell Line, Tumor ; Chemotherapy, Adjuvant ; Colorectal Neoplasms/drug therapy/immunology ; Dendritic Cells/drug effects/immunology ; Female ; Humans ; Immunity, Innate/genetics ; Leukocytes/drug effects/immunology ; Mice ; Neoplasms/*drug therapy/*immunology ; Polymorphism, Single Nucleotide ; Receptors, Formyl Peptide/genetics/*physiology ; T-Lymphocytes/immunology
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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