Signals trigger state-specific transcriptional programs to support diversity and homeostasis in immune cells.
Sci Signal
; 12(581)2019 05 14.
Article
em En
| MEDLINE
| ID: mdl-31088978
ABSTRACT
Macrophages play key roles in the immune systems of humans and other mammals. Here, we performed single-cell analyses of the mRNAs and proteins of human macrophages to compare their responses to the signaling molecules lipopolysaccharide (LPS), a component of Gram-negative bacteria, and palmitate (PAL), a free fatty acid. We found that, although both molecules signal through the cell surface protein Toll-like receptor 4 (TLR4), they stimulated the expression of different genes, resulting in specific pro- and anti-inflammatory cellular states for each signal. The effects of the glucocorticoid receptor, which antagonizes LPS signaling, and cyclic AMP-dependent transcription factor 3, which inhibits PAL-induced inflammation, on inflammatory response seemed largely determined by digital on-off events. Furthermore, the quantification of transcriptional variance and signaling entropy enabled the identification of cell state-specific deregulated molecular pathways. These data suggest that the preservation of signaling in distinct cells might confer diversity on macrophage populations essential to maintaining major cellular functions.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Transcrição Gênica
/
Variação Genética
/
Transdução de Sinais
/
Homeostase
/
Macrófagos
Tipo de estudo:
Prognostic_studies
Limite:
Humans
Idioma:
En
Revista:
Sci Signal
Ano de publicação:
2019
Tipo de documento:
Article