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dc.contributor.author
Taves, Matthew D.
dc.contributor.author
Mittelstadt, Paul R.
dc.contributor.author
Presman, Diego Martin
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Hager, Gordon L.
dc.contributor.author
Ashwell, Jonathan D.
dc.date.available
2020-12-23T16:45:55Z
dc.date.issued
2019-03
dc.identifier.citation
Taves, Matthew D.; Mittelstadt, Paul R.; Presman, Diego Martin; Hager, Gordon L.; Ashwell, Jonathan D.; Single-Cell Resolution and Quantitation of Targeted Glucocorticoid Delivery in the Thymus; Elsevier; Cell Reports; 26; 13; 3-2019; 3629-3642.e4
dc.identifier.issn
2211-1247
dc.identifier.uri
http://hdl.handle.net/11336/121140
dc.description.abstract
Glucocorticoids are lipid-soluble hormones that signal via the glucocorticoid receptor (GR), a ligand-dependent transcription factor. Circulating glucocorticoids derive from the adrenals, but it is now apparent that paracrine glucocorticoid signaling occurs in multiple tissues. Effective local glucocorticoid concentrations and whether glucocorticoid delivery can be targeted to specific cell subsets are unknown. We use fluorescence detection of chromatin-associated GRs as biosensors of ligand binding and observe signals corresponding to steroid concentrations over physiological ranges in vitro and in vivo. In the thymus, where thymic epithelial cell (TEC)-synthesized glucocorticoids antagonize negative selection, we find that CD4 + CD8 + TCR hi cells, a small subset responding to self-antigens and undergoing selection, are specific targets of TEC-derived glucocorticoids and are exposed to 3-fold higher levels than other cells. These results demonstrate and quantitate targeted delivery of paracrine glucocorticoids. This approach may be used to assess in situ nuclear receptor signaling in a variety of physiological and pathological contexts. Glucocorticoids signal via the GR, a ligand-dependent transcription factor, and paracrine glucocorticoid signaling occurs in the thymus. Taves et al. use chromatin-associated GRs as biosensors to estimate glucocorticoid concentrations in vitro and in vivo. In the thymus, antigen-signaled CD4 + 8 + TCR hi cells are targeted by epithelial cell-synthesized glucocorticoids to promote positive selection.
dc.format
application/pdf
dc.language.iso
eng
dc.publisher
Elsevier
dc.rights
info:eu-repo/semantics/openAccess
dc.rights.uri
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.subject
CYP11B1
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GLUCOCORTICOID RECEPTOR
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GLUCOCORTICOIDS
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LYMPHOCYTES
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NUCLEAR RECEPTORS
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PARACRINE
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STEROIDOGENESIS
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STEROIDS
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TRANSCRIPTION FACTOR
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Bioquímica y Biología Molecular
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Ciencias Biológicas
dc.subject.classification
CIENCIAS NATURALES Y EXACTAS
dc.title
Single-Cell Resolution and Quantitation of Targeted Glucocorticoid Delivery in the Thymus
dc.type
info:eu-repo/semantics/article
dc.type
info:ar-repo/semantics/artículo
dc.type
info:eu-repo/semantics/publishedVersion
dc.date.updated
2020-11-13T20:47:49Z
dc.journal.volume
26
dc.journal.number
13
dc.journal.pagination
3629-3642.e4
dc.journal.pais
Estados Unidos
dc.description.fil
Fil: Taves, Matthew D.. National Cancer Institute; Estados Unidos
dc.description.fil
Fil: Mittelstadt, Paul R.. National Cancer Institute; Estados Unidos
dc.description.fil
Fil: Presman, Diego Martin. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Fisiología, Biología Molecular y Neurociencias. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Fisiología, Biología Molecular y Neurociencias; Argentina. National Cancer Institute; Estados Unidos
dc.description.fil
Fil: Hager, Gordon L.. National Cancer Institute; Estados Unidos
dc.description.fil
Fil: Ashwell, Jonathan D.. National Cancer Institute; Estados Unidos
dc.journal.title
Cell Reports
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/url/https://www.cell.com/cell-reports/fulltext/S2211-1247(19)30294-3?_returnURL=https%3A%2F%2Flinkinghub.elsevier.com%2Fretrieve%2Fpii%2FS2211124719302943%3Fshowall%3Dtrue
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/doi/http://dx.doi.org/10.1016/j.celrep.2019.02.108
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