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Gene Regulatory Programs Conferring Phenotypic Identities to Human NK Cells

Collins, Patrick L. ; Cella, Marina ; Porter, Sofia I. ; Li, Shasha ; Gurewitz, Greer L. ; Hong, Henoch S. ; Johnson, R. Paul ; Oltz, Eugene M. ; Colonna, Marco

Cell, 2019-01, Vol.176 (1-2), p.348-360.e12 [Periódico revisado por pares]

United States: Elsevier Inc

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  • Título:
    Gene Regulatory Programs Conferring Phenotypic Identities to Human NK Cells
  • Autor: Collins, Patrick L. ; Cella, Marina ; Porter, Sofia I. ; Li, Shasha ; Gurewitz, Greer L. ; Hong, Henoch S. ; Johnson, R. Paul ; Oltz, Eugene M. ; Colonna, Marco
  • Assuntos: Cytokines - immunology ; Cytokines - metabolism ; Gene Expression Regulation - genetics ; Gene Expression Regulation - immunology ; Humans ; Killer Cells, Natural - classification ; Killer Cells, Natural - immunology ; Killer Cells, Natural - physiology ; Phenotype
  • É parte de: Cell, 2019-01, Vol.176 (1-2), p.348-360.e12
  • Notas: ObjectType-Article-1
    SourceType-Scholarly Journals-1
    ObjectType-Feature-2
    content type line 23
    Conceptualization, E.M.O. and M. Colonna; Methodology, M. Cella and P.L.C.; Investigation, P.L.C., M. Cella, S.L., S.I.P, H.H., and R.P.J.; Visualization, P.L.C., G.L.G.; Writing, E.M.O, M. Colonna, M. Cella, and P.L.C.; Data Curation, Software and Formal Analysis, P.L.C.; Supervision, E.M.O. and M. Colonna
    AUTHOR CONTRIBUTIONS
  • Descrição: Natural killer (NK) cells develop from common progenitors but diverge into distinct subsets, which differ in cytokine production, cytotoxicity, homing, and memory traits. Given their promise in adoptive cell therapies for cancer, a deeper understanding of regulatory modules controlling clinically beneficial NK phenotypes is of high priority. We report integrated “-omics” analysis of human NK subsets, which revealed super-enhancers associated with gene cohorts that may coordinate NK functions and localization. A transcription factor-based regulatory scheme also emerged, which is evolutionarily conserved and shared by innate and adaptive lymphocytes. For both NK and T lineages, a TCF1-LEF1-MYC axis dominated the regulatory landscape of long-lived, proliferative subsets that traffic to lymph nodes. In contrast, effector populations circulating between blood and peripheral tissues shared a PRDM1-dominant landscape. This resource defines transcriptional modules, regulated by feedback loops, which may be leveraged to enhance phenotypes for NK cell-based therapies. [Display omitted] •Regulome analysis reveals a spectrum of molecular programs for human ILC1-NK cells•Conserved regulatory schemes for localization-function shared by NK and T cells•TCF1-MYC enforce progenitor-like, lymph node localization modules•PRDM1-ZEB2-MAF dominate effector and non-lymphoid localization programs A combination of single-cell and systems biology approaches determines the molecular programs defining the identity and function of human tissue resident type I innate lymphoid cells and natural killer cells.
  • Editor: United States: Elsevier Inc
  • Idioma: Inglês
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  • Realização: ABCD-USP USP   Logos de Redes Sociais: Freepik

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