Differentiation and specification of resident tissue macrophages


Tissue resident macrophages are functionally diverse cells that share an embryonic mesodermal origin. However, the mechanism(s) that control their specification remain unclear. We performed transcriptional, molecular and in situ spatio-temporal analyses of macrophage development in mice. We report that Erythro-Myeloid Progenitors generate pre-macrophages (pMacs) that simultaneously colonize the head and caudal embryo from embryonic day (E)9.5 in a chemokine-receptor dependent manner, to further differentiate into tissue F4/80+ macrophages. After its initiation in pMacs, the core macrophage transcriptional program is rapidly diversified in early macrophages as expression of transcriptional regulators becomes tissue-specific. For example, the preferential expression of the transcriptional regulator Id3 initiated in early fetal liver macrophages appears critical for Kupffer cell differentiation, as inactivation of Id3 causes a selective Kupffer cell deficiency that persists in adults. We propose that colonization of developing tissues by differentiating macrophages is immediately followed by their specification as they establish residence, hereby generating the macrophage diversity observed in post-natal tissues.

Data visualization: Interactive genome browser view of resident macrophage differentiation

Name Description and link
RNA-seq: 100 cell pools, SMART-seq2

Data analysis results: Gene expression values and lists of signature genes

Name Description and download
RNA-seq (SMART-seq2) expression matrix Normalized transcript-level expression estimates for all reliably detected transcripts
Differentially expressed genes: EMP vs. pMac vs. Mac Lists of up-regulated genes in progenitors, pMacs, and Macs
Differentially expressed genes: Resident macrophages Lists of up-regulated genes in macrophages resident in postnatal liver, lung, brain, skin, and kidney

Data access: All raw data are available from GEO

Name Accession numbers and links
Gene Expression Omnibus (GEO)


If you use this resource in your research, please cite:

Elvira Mass*, Ivan Ballesteros*, Matthias Farlik*, Florian Halbritter*, Patrick Gunther*, Lucile Crozet, Christian E Jacome-Galarza, Johanna Klughammer, Yasuhiro Kobayashi, Elisa Gomez-Perdiguero, Joachim Schultze, Marc Beyer#, Christoph Bock# & Frederic Geissmann#. Differentiation and specification of resident tissue macrophages. Science, 4 August 2016. DOI:10.1126/science.aaf4238, PubMed: 27492475
* Shared first authors
# Shared last authors