Distinct and temporary-restricted epigenetic mechanisms regulate human αß and γδ T cell development.
Nat Immunol
; 21(10): 1280-1292, 2020 10.
Article
em En
| MEDLINE
| ID: mdl-32719521
ABSTRACT
The development of TCRαß and TCRγδ T cells comprises a step-wise process in which regulatory events control differentiation and lineage outcome. To clarify these mechanisms, we employed RNA-sequencing, ATAC-sequencing and ChIPmentation on well-defined thymocyte subsets that represent the continuum of human T cell development. The chromatin accessibility dynamics show clear stage specificity and reveal that human T cell-lineage commitment is marked by GATA3- and BCL11B-dependent closing of PU.1 sites. A temporary increase in H3K27me3 without open chromatin modifications is unique for ß-selection, whereas emerging γδ T cells, which originate from common precursors of ß-selected cells, show large chromatin accessibility changes due to strong T cell receptor (TCR) signaling. Furthermore, we unravel distinct chromatin landscapes between CD4+ and CD8+ αß-lineage cells that support their effector functions and reveal gene-specific mechanisms that define mature T cells. This resource provides a framework for studying gene regulatory mechanisms that drive normal and malignant human T cell development.
Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
Linfócitos T
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Receptores de Antígenos de Linfócitos T gama-delta
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Receptores de Antígenos de Linfócitos T alfa-beta
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Timócitos
Limite:
Humans
Idioma:
En
Ano de publicação:
2020
Tipo de documento:
Article