Bone marrow-derived monocytes give rise to self-renewing and fully differentiated Kupffer cells
Open accessAbstract
Self-renewing tissue-resident macrophages are thought to be exclusively derived from embryonic progenitors. However, whether circulating monocytes can also give rise to such macrophages has not been formally investigated. Here we use a new model of diphtheria toxin-mediated depletion of liver-resident Kupffer cells to generate niche availability and show that circulating monocytes engraft in the liver, gradually adopt the transcriptional profile of their depleted counterparts and become long-lived self-renewing cells. Underlining the physiological relevance of our findings, circulating monocytes also contribute to the expanding pool of macrophages in the liver shortly after birth, when macrophage niches become available during normal organ growth. Thus, like embryonic precursors, monocytes can and do give rise to self-renewing tissue-resident macrophages if the niche is available to them.
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Infiltrating monocytes compete with Kupffer cells for survival signals like CSF-1.
“In addition to competing for survival signals like CSF-1 (9, 33, 34), infiltrating monocytes actively replace embryonic KCs (EmKCs) during injury (35–37).”
From Macrophage duality in liver diseases: heterogeneity, plasticity, and the quest for precision therapeutics (2026) · cites this paper as [33]
The Results section, “Mo-KCs compete with em-KCs for KC niche repopulation” (page not provided), says that recruited monocytes compete with remaining embryonic Kupffer cells for niche occupancy after partial depletion. It does not identify competition for survival signals, including CSF-1, as the mechanism; the Discussion instead calls for research into the signals regulating repopulation. (LLM, conf=0.87)
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“MDMs that occupy the KC niche become what is termed monocyte-derived KCs (MoKCs), expressing all KC markers except TIM4, although as a maker of residency, this can also be acquired over time (25, 104).”
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- Authors
- Scott, C. L., Zheng, F., De Baetselier, P., Martens, L., Saeys, Y., De Prijck, S., Lippens, S., Abels, C., Schoonooghe, S., Raes, G., Devoogdt, N., Lambrecht, B. N., Beschin, A., & Guilliams, M.
- Affiliations
- Ghent University (BE)
- Vrije Universiteit Brussel (BE)
- Corresponding author
- Guilliams, Martin
- ORCID
- Venue
- Nature Communications
- Published
- 2016-01-27
- Volume
- 7
- Issue
- 1
- Pages
- 10321-10321
- ISSN
- 2041-1723 (ISSN-L)
- PMC
- PMC4737801
- OpenAlex
- W2343063221
- Cited by
- 860
- References
- 10
- Citations by year
- 2026: 57 · 2025: 106 · 2024: 86 · 2023: 96 · 2022: 95 · 2021: 102 · 2020: 98 · 2019: 58 · 2018: 83 · 2017: 58 · 2016: 21
- FWCI
- 53.04
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Nature Communications (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Ghent University Academic Bibliography (Ghent University) (submittedVersion, cc-by)
- RePEc: Research Papers in Economics (submittedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- VUBIR (Vrije Universiteit Brussel) (submittedVersion)
- Funders
- Fonds Wetenschappelijk Onderzoek
- Topics
- Health Sciences › Medicine › Hepatology › Liver physiology and pathology
- Life Sciences › Immunology and Microbiology › Immunology › Immune cells in cancer
- Health Sciences › Medicine › Genetics › Mesenchymal stem cell research
- Keywords
- Kupffer cells, tissue-resident macrophages, bone marrow-derived monocytes, self-renewal
- MeSH terms
- Cell Self Renewal, Animals, Bone Marrow Cells, Cell Differentiation, Cells, Cultured, Female, Kupffer Cells, Male, Mice, Inbred C57BL, Monocytes, Mice
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