Dataset Information

Single-cell response to LPS of wild-type and cohesin-deficient macrophages.

ABSTRACT: Transcription is an intermittent process that occurs in bursts. The frequency and the number of messenger RNA (mRNA) produced by these bursts determine expression levels and shape cell-to-cell variability. Productive encounters between enhancers and promoters control burst dynamics, which the cohesin complex can facilitate through loop extrusion. Cohesin is a ring-shaped complex involved in enhancer-promoter interactions. Without cohesin, bone-marrow-derived macrophages' transcriptional response to LPS is severely impaired (Cuartero et al., 2018). Single-cell RNA sequencing (scRNAseq) showed that the frequency of cells expressing inducible transcripts (as defined in Bhatt et al., 2012) was reduced in cohesion-deficient macrophages before and after LPS stimulation. In contrast, when considering only cells expressing LPS-inducible transcripts, cohesin-deficient macrophages showed reduced mean expression at baseline and late LPS-response (8h) but not in the early response (2h). These results support a model where cohesin is implicated in the control of burst frequencies upon LPS.

ORGANISM(S): Mus musculus

PROVIDER: GSE190622 | GEO | 2022/04/17

REPOSITORIES: GEO

ACCESS DATA

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Project description:Toll like receptor 4 (TLR4), an innate immunity gene, is involved in responses to several pulmonary agonists including endotoxin (LPS; Poltorak et al.,1998), ozone (O3 ,Kleeberger et. al., 2001), Pseudomonas aeruginosa (Faure et al, 2004), and hyperoxia (Zhang et al, 2005). TLR4 appears to partially mediate the response to LPS- and O3-induced lung injury, however, TLR4 is protective for prevention of injury in Pseudomonas aeruginosa infection and against acute lung injury (hyperoxia). The mechanism behind this protection is unclear. We previously demonstrated that TLR4 was also protective against BHT-induced chronic inflammation and tumor promotion (Bauer et al, 2005). C.C3H-Tlr4Lps-d (BALBLps-d) mice, congenic for a 10 cM region of C3H/HeJ chromosome 4 that contains Tlr4 (Vogel et al, 1994), have a missence mutation that renders TLR4 dysfunctional. The Tlr4 mutation likely abrogates signaling by disrupting a direct point of contact with other signaling molecules (Akira S, Takeda K. Toll-like receptor signalling. Nat Rev Immunol 2004;4(7):499-511.). Bronchoalveolar lavage fluid (BALF) alveolar macrophages, lymphocytes, and total protein content were significantly elevated in BALBLps-d mice compared to BALB/c (BALB; Tlr4 sufficient) mice following chronic BHT (Bauer et al., 2005). BALBLps-d mice also had a significant increase in tumor multiplicity (60%) over that of BALB mice in response to an MCA/BHT tumor promotion protocol. While this was the first model to demonstrate a protective role for TLR4 in chronic lung inflammation and tumorigenesis, the downstream mechanism regulating this protective response remains unknown. Using Affymetrix microarray analysis followed by GeneSpring and Ingenuity pathway analyses, we herein identified known and novel downstream pathways and their interactions that may be involved in the protective mechanism elicited by TLR4. We therefore hypothesize that these pathways and interactions amongst the genes identified during the tumor promotion/chronic inflammation stage are in part influencing the differential strain response observed during tumorigenesis. Keywords: time course, tumor study

Dataset Information

Single-cell response to LPS of wild-type and cohesin-deficient macrophages.

Dataset's files

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets