Bone marrow-derived monocytes give rise to self-renewing and fully differentiated Kupffer cells

Nature Communications
Charlotte L ScottMartin Guilliams

Abstract

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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Datasets Mentioned

BETA
GSE75225

Methods Mentioned

BETA
PCR
ELISAs
surface plasmon resonance
flow cytometry

Software Mentioned

Prism
BioGPS
FlowJo
TreeStar
GraphPad

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