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Gene-expression profiles and transcriptional regulatory pathways that underlie the identity and diversity of mouse tissue macrophages


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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Figure 1: Analysis of macrophage diversity.
Figure 2: Unique gene-expression profiles of macrophages from various organs.
Figure 3: Identification of gene modules enriched for macrophage-related gene signatures and their predicted regulators.
Figure 4: Expression of genes of the macrophage core signature by other populations of mononuclear phagocytes.
Figure 5: Transcripts of the macrophage core signature, assessed as protein in various tissues.

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We thank our colleagues of the ImmGen Project consortium; V. Jojic, J. Ericson, S. Davis and C. Benoist for contributions; eBioscience and Affymetrix for material support of the ImmGen Project; and M. Colonna (Washington University School of Medicine) for monoclonal antibodies (including anti-Siglec-H) and other reagents. Supported by the National Institute of Allergy and Infectious Diseases of the US National Institutes of Health (R24 AI072073 to fund the ImmGen Project, spearheaded by C. Benoist), the US National Institutes of Health (R01AI049653 and R01AI061741 to G.J.R.; P50GM071558-03 and R01DK08854 to A.M.; and5T32DA007135-27 to A.R.M.) and the American Heart Association (10POST4160140 to E.L.G.).

Author information





E.L.G. purified macrophage populations, designed and did experiments, analyzed data and wrote the manuscript; G.J.R. designed and supervised experiments, analyzed data and wrote the manuscript; T.S. analyzed data and wrote the manuscript; J.M. designed analytical strategies and analyzed data; M.G., C.J., J.H., A.C. and K.G.E. purified macrophage and DC populations; S.I. did experiments; S.G., A.R.M. and A.M. analyzed data; W.-J.C. and T.H.H. provided reagents and supervised experiments; and S.J.T. and M.M. designed and supervised experiments.

Corresponding author

Correspondence to Gwendalyn J Randolph.

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The authors declare no competing financial interests.

Supplementary information

Supplementary Text and Figures

Supplementary Figures 1–6, Tables 1 and 4–6 and Notes 1–2 (PDF 3836 kb)

Supplementary Table 2

Probeset levels of the macrophage core signature genes. (XLS 27 kb)

Supplementary Table 3

Probeset levels of the extended macrophage core signature genes. (XLS 77 kb)

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Gautier, E., Shay, T., Miller, J. et al. Gene-expression profiles and transcriptional regulatory pathways that underlie the identity and diversity of mouse tissue macrophages. Nat Immunol 13, 1118–1128 (2012).

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