Gene expression profiles and transcriptional regulatory pathways underlying mouse tissue macrophage identity and diversity

By E. Gautier, T. Shay, Jennifer Miller, M. Greter, Claudia V. Jakubzick, Stoyan Ivanov, J. Helft, A. Chow, Kutlu G. Elpek, S. Gordonov and 7 more. Nature Immunology, 2012

1,860 citations recorded by the source corpus.

We assessed gene expression in tissue macrophages from various mouse organs. The diversity in gene expression among different populations of macrophages was considerable. Only a few hundred mRNA transcripts were selectively expressed by macrophages rather than dendritic cells, and many of these were not present in all macrophages. Nonetheless, well-characterized surface markers, including MerTK and FcγR1 (CD64), along with a cluster of previously unidentified transcripts, were distinctly and universally associated with mature tissue macrophages. TCEF3, C/EBP-α, Bach1 and CREG-1 were among the transcriptional regulators predicted to regulate these core macrophage-associated genes. The mRNA encoding other transcription factors, such as Gata6, was associated with single macrophage populations. We further identified how these transcripts and the proteins they encode facilitated distinguishing macrophages from dendritic cells.

Subfields: Immunology, Neurology

View Paper: https://www.semanticscholar.org/paper/ccab94bdb9fa57cbf1371cec8c40ce0ba4419512

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Immunology

1. A. Mantovani
2. S. Gordon
3. A. Sica
4. P. Murray
5. R. Medzhitov
6. P. Italiani
7. D. Boraschi
8. TA Wynn

In Neurology

1. R. Ransohoff
2. A. Mantovani
3. P. Murray
4. S. Gordon
5. TA Wynn
6. Marco Prinz
7. D. Holtzman
8. A. Sica

Citations in the corpus

• The microenvironmental landscape of brain tumors (2017, background): “Cx3cr1 and Siglec-H are also expressed by normal microglia, but not by macrophages derived from lung, peritoneum or spleen (Gautier et al., 2012).”
• The Role of Short-Chain Fatty Acids From Gut Microbiota in Gut-Brain Communication (2020, background): “Although the mechanisms involved in the control of maturation and function of microglia by SCFAs remain to be determined, the activation of FFAR2 could be conceivable since FFAR2-deficient mice displayed microglia reminiscent of those found in GF mice (103).”
• The role of macrophages in the resolution of inflammation. (2019, background): “Mice deficient in CCR2 are therefore monocytopenic and fail to recruit monocytes and monocyte-derived macrophages to tissues during liver — had more differences in their transcriptional program than similarities (23).”
• Macrophage Polarization: Different Gene Signatures in M1(LPS+) vs. Classically and M2(LPS–) vs. Alternatively Activated Macrophages (2019, background): “Since the discovery of tissue-specific gene signatures in peritoneal macrophages (6), many published transcriptomic data show that each tissue macrophage set has both tissue-specific and shared gene signatures, based on the tissue of origin (7).”
• Macrophage heterogeneity in tissues: phenotypic diversity and functions (2014, background): “reported in 2012 (157), as part of the Immgen project, on the identity and differences in mouse tissue macrophages; four populations were assessed as a whole, peritoneal, red pulp splenic, lung macrophages, and microglia.”
• Microglial M1/M2 polarization and metabolic states (2016, background): “Tissue-specific macrophages can be found in virtually all tissues of the body and are representative of distinct classes (Gautier et al., 2012).”
• Exosome-Based Cell-Cell Communication in the Tumor Microenvironment (2018, background): “In general, based on Th1/Th2 polarization, M1 macrophages are pro-inflammatory and tumoricidal (classically activated), while M2 are anti-inflammatory and tumor supportive (alternatively activated) (Martinez et al., 2008; Gautier et al., 2012; Xue et al., 2014; You et al., 2015).”