Signals trigger state-specific transcriptional programs to support diversity and homeostasis in immune cells

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216224%3A14740%2F19%3A00113240" target="_blank" >RIV/00216224:14740/19:00113240 - isvavai.cz</a>

Výsledek na webu

<a href="https://stke.sciencemag.org/content/12/581/eaao5820" target="_blank" >https://stke.sciencemag.org/content/12/581/eaao5820</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1126/scisignal.aao5820" target="_blank" >10.1126/scisignal.aao5820</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Signals trigger state-specific transcriptional programs to support diversity and homeostasis in immune cells

Popis výsledku v původním jazyce

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.

Název v anglickém jazyce

Signals trigger state-specific transcriptional programs to support diversity and homeostasis in immune cells

Popis výsledku anglicky

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.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

10608 - Biochemistry and molecular biology

Projekt

—

Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2019

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

SCIENCE SIGNALING

ISSN

1945-0877

e-ISSN

—

Svazek periodika

12

Číslo periodika v rámci svazku

581

Stát vydavatele periodika

US - Spojené státy americké

Počet stran výsledku

16

Strana od-do

1-16

Kód UT WoS článku

000467963000001

EID výsledku v databázi Scopus

2-s2.0-85066279813