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Gene-expression profiles and transcriptional regulatory pathways that underlie the identity and diversity of mouse tissue macrophages
Open accessAbstract
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.
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“Microglia also express hundreds of genes at higher levels than other macrophage subsets (24–26) that may be influenced by factors present in the CNS microenvironment (25, 27), suggesting mechanisms by which the brain environment influences the activity and functions of one of its primary support cells.”
From An environment-dependent transcriptional network specifies human microglia identity (2017) · cites this paper as [24]
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“Recent work demonstrated that all tissue resident macrophages are different to an extent yet cluster together when compared to monocytes and DCs and that spleen red pulp macrophages were closely associated with microglia14.”
From Identification of a unique TGF-β–dependent molecular and functional signature in microglia (2014) · cites this paper as [14]
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“We also found that organ-resident macrophages in the gut and liver are “microglia-like” as they express Gas6 and Mertk and these genes may have a role in maintaining tissue homeostasis which is consistent with a recent transcriptional profiling of murine tissue macrophages14.”
From Identification of a unique TGF-β–dependent molecular and functional signature in microglia (2014) · cites this paper as [14]
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“FFAR2-deficient mice displayed microglia reminiscent of those found in GF mice (103).”
From The Role of Short-Chain Fatty Acids From Gut Microbiota in Gut-Brain Communication (2020) · cites this paper as [103]
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“we found increased microglial expression of C1q, Csfr1 and Cd34 genes, which are known to be expressed on tissue resident macrophages14.”
From Identification of a unique TGF-β–dependent molecular and functional signature in microglia (2014) · cites this paper as [14]
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“Because macrophages and dendritic cells have similar transcriptomic profiles23–25, we repeated SingleR analysis using published RNA-seq datasets of mouse lung macrophages and dendritic cells26,27 to isolate the macrophages”
From Reference-based analysis of lung single-cell sequencing reveals a transitional profibrotic macrophage (2019) · cites this paper as [25]
In the citing paper
“microglia — but not peripheral myeloid cells — were shown to express P2Y purinoceptor 12 (P2ry12), transmembrane protein 119 (Tmem119), sialic acid binding Ig-like lectin H (Siglech), probable G protein coupled receptor 34 (Gpr34), suppressor of cytokine signalling 3 (Socs3), β-hexosaminidase subunit β (Hexb), olfactomedin-like protein 3 (Olfml3) and Fc receptor-like S, scavenger receptor (Fcrls).”
From Microglial signatures and their role in health and disease (2018) · cites this paper as [29]
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“In the healthy brain, they exhibit a unique molecular homeostatic ‘signature’, consisting of a specific transcriptional profile and surface protein expression pattern, which differs from that of tissue macrophages.”
From Microglial signatures and their role in health and disease (2018) · cites this paper as [29]
In the citing paper
“Tissue micro-environmental factors activate cascades resulting in co-operative binding of certain transcription factors with PU.1, leading to a unique enhancer profile enabling microglial dynamic response to its surrounding micro-environment [24, 72].”
From Transcriptional and Epigenetic Regulation of Microglia in Health and Disease (2019) · cites this paper as [72]
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BackgroundMethodResultFlow Cytometric Analysis of Macrophages and Dendritic Cell Subsets in the Mouse Lung
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Bone marrow-derived monocytes give rise to self-renewing and fully differentiated Kupffer cells
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BackgroundThe human heart contains distinct macrophage subsets with divergent origins and functions
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BackgroundNeuro-immune Interactions Drive Tissue Programming in Intestinal Macrophages
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Self-citationMacrophage Ontogeny Underlies Differences in Tumor-Specific Education in Brain Malignancies
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“A useful approach to this comes from recent work that has demonstrated that expression of CD64 (the high affinity FcRc1), F4/80 and MerTK (12, 16, 17), can be used in combination with CD11c and MHCII to define functionally distinct MP populations in mice.”
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“Microglia, the tissue macrophages of the brain, also express Axl and Mer (Gautier et al. 2012), and there is evidence that TAM signaling through these receptors controls the phagocytosis of ACs and the inhibition of inflammation in the CNS just as it does in macrophages and DCs in the periphery (Grommes et al.”
Background
Metadata
- Authors
- the Immunological Genome Consortium, Gautier, E. L., Shay, T., Miller, J., Greter, M., Jakubzick, C., Ivanov, S., Helft, J., Chow, A., Elpek, K. G., Gordonov, S., Mazloom, A. R., Ma'ayan, A., Chua, W.-J., Hansen, T. H., Turley, S. J., Merad, M., & Randolph, G. J.
- Affiliations
- Icahn School of Medicine at Mount Sinai (US)
- Broad Institute (US)
- Mount Sinai Hospital (US)
- Washington University in St. Louis (US)
- Harvard University (US)
- Corresponding author
- Randolph, Gwendalyn J
- ORCID
- Venue
- Nature Immunology
- Published
- 2012-09-30
- Volume
- 13
- Issue
- 11
- Pages
- 1118-1128
- ISSN
- 1529-2908 (ISSN-L)
- 1529-2916
- PMC
- PMC3558276
- OpenAlex
- W2136188258
- Cited by
- 1,972
- References
- 41
- Citations by year
- 2026: 71 · 2025: 88 · 2024: 104 · 2023: 113 · 2022: 152 · 2021: 174 · 2020: 177 · 2019: 155 · 2018: 183 · 2017: 190 · 2016: 159 · 2015: 170 · 2014: 140 · 2013: 90 · 2012: 4
- FWCI
- 56.29
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Immunology (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- HAL (submittedVersion)
- DSpace@MIT (Massachusetts Institute of Technology) (submittedVersion, cc-by-nc-sa)
- eScholarship (California Digital Library) (submittedVersion)
- Funders
- National Institute on Drug Abuse (T32DA007135)
- National Cancer Institute (R01CA154947)
- National Institute of General Medical Sciences (P50GM071558, R01GM098316)
- National Institute of Allergy and Infectious Diseases (R01AI049653, R01AI046553, R01AI061741, R24AI072073)
- National Institute of Diabetes and Digestive and Kidney Diseases (R01DK08854, P30DK020579)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Immune cells in cancer
- Life Sciences › Immunology and Microbiology › Immunology › Phagocytosis and Immune Regulation
- Life Sciences › Immunology and Microbiology › Immunology › Atherosclerosis and Cardiovascular Diseases
- Keywords
- tissue macrophages, macrophage heterogeneity, gene expression profiling, macrophage identity, dendritic cells, MERTK, C/EBPα, BACH1, GATA6, mouse organs
- MeSH terms
- Animals, Cell Differentiation, Dendritic Cells, Gene Expression Regulation, Liver, Lung, Macrophages, Organ Specificity, RNA, Messenger, Spleen, Transcription Factors, Transcription, Genetic, Genetic Variation, Antigens, CD, Microglia, Oligonucleotide Array Sequence Analysis, Gene Expression Profiling, Mice
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