Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

Transcriptional profiling by array of infiltrating macrophages from injured muscles of Cebpb promoter mutant mice

ABSTRACT: Gene expression of macrophages from injured muscles of bDCRE mutant mice was compared with that of Cebpb wt mice. Skeletal muscles were injured by cardiotoxin injection and infiltrating macrophages were isolated 6 days post-injury by FACS sorting of Mac-1+F4/80+ cells. 4 biological replicates were generated for each genotype and expression profiles were determined by hybridization to Affymetrix Moe430_2 arrays.

ORGANISM(S): Mus musculus

SUBMITTER: Claus Nerlov

PROVIDER: E-TABM-755 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

A CREB-C/EBPbeta cascade induces M2 macrophage-specific gene expression and promotes muscle injury repair.

Ruffell Daniela D Mourkioti Foteini F Gambardella Adriana A Kirstetter Peggy P Lopez Rodolphe G RG Rosenthal Nadia N Nerlov Claus C

Proceedings of the National Academy of Sciences of the United States of America 20090924 41

Macrophages play an essential role in the resolution of tissue damage through removal of necrotic cells, thus paving the way for tissue regeneration. Macrophages also directly support the formation of new tissue to replace the injury, through their acquisition of an anti-inflammatory, or M2, phenotype, characterized by a gene expression program that includes IL-10, the IL-13 receptor, and arginase 1. We report that deletion of two CREB-binding sites from the Cebpb promoter abrogates Cebpb induct ...[more]

PMID: 19805133

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Project description:The CCAAT/enhancer-binding proteins (CEBPs) are transcription factors involved in hematopoietic cell development and induction of several inflammatory mediators. Here, we generated CEBP-beta (CEBPB) and CEBP-epsilon (CEBPE) double-knockout (bbee) mice and compared their phenotypes to those of single-deficient (bbEE and BBee) and wild-type (BBEE) mice. The bbee mice were highly susceptible to fatal infections and died within 2-3 months. Morphologically, their neutrophils were blocked at the myelocytes/metamyelocytes stage, and clonogenic assays of bone marrow cells indicated a significant decrease in the number of myeloid colonies of the bbee mice. In addition, the proportion of hematopoietic progenitor cells [Lin(-)Sca1(+)c-Kit(+)] in the bone marrow of the bbee mice was significantly increased, reflecting the defective differentiation of the myeloid compartment. Furthermore, microarray expression analysis of lipopolysaccharide (LPS)- and interferon-gamma (IFN-gamma)-activated bone marrow-derived macrophages from bbee compared to single knockout mice revealed decreased expression of essential immune response-related genes and networks, including some direct CEBP targets such as Marco and Clec4e. Overall, the phenotype of the bbee mice is distinct from either the bbEE or BBee mice, demonstrating that both transcription factors are crucial for the maturation of neutrophils and macrophages, as well as the innate immune system, and can at least in part compensate for each other in the single knockout mice. To rule out the regulatory influence of both CEBPB and CEBPE on macrophage-related genes, expression analysis of bone marrow-derived macrophages was performed. Macrophages were derived from murine bone marrow with the use of murine M-CSF. The macrophages were stimulated with both LPS (100 ng) and IFN-gamma (100 ng) for 24h, and RNA was extracted for array analysis. Overall, RNA was extracted from stimulated macrophages of one WT mouse, one CEBPB-KO mouse, one CEBPE-KO mouse and one double-KO mouse.

Dataset Information

Transcriptional profiling by array of infiltrating macrophages from injured muscles of Cebpb promoter mutant mice

Publications

A CREB-C/EBPbeta cascade induces M2 macrophage-specific gene expression and promotes muscle injury repair.

Similar Datasets

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