Martin Guilliams - Kupffer Cell Niche

Martin GuilliamsMartin Guilliams obtained his PhD at the Free University of Brussels (VIB-VUB), in the Lab of Patrick De Baetselier and did his first postdoc at Centre d'Immunologie Marseille-Luminy (CIML, Marseille, France) in the lab of Bernard Malissen and his second postdoc at the VIB Center for Inflammation Research (IRC, Ghent University - VIB, Belgium) in the lab of Bart Lambrecht. In 2015 he obtained a Tenure-Track Professorship at the Ghent University.

In 2017 he obtained an ERC Consolidator Grant and became an independent Principal Investigator at the VIB (VIB PI). He leads a research team that focuses on the functional specialization of macrophages in homeostasis and disease within the VIB Center for Inflammation Research (IRC, Ghent University, Belgium).





Determining the instructive tissue signals and the master transcription factors driving Kupffer cell differentiation (Kupffer Cell Niche)

We have recently shown that contrary to common hypotheses, circulating monocytes can efficiently differentiate into Kupffer cells (KCs), the liver-resident macrophages. Using self-generated knock-in mice that allow specific KC depletion, we found that monocytes colonize the KC niche in a single wave upon KC depletion and rapidly differentiate into self-maintaining KCs that are transcriptionally and functionally identical to their embryonic counterparts.

Kupffer Cell Niche

This implies that: (i) access to the KC niche is tightly regulated ensuring that monocytes do not differentiate into KCs when the KC niche is full but differentiate very efficiently into KCs upon temporary niche availability, (ii) imprinting by the KC niche is the dominant factor conferring KC identity. Understanding which cells constitute the macrophage niche, which signals produced by these cells imprint the tissue-specific macrophage gene expression profile and through which transcription factors (TxFs) this is mediated is emerging as the next challenge in the field. We here propose an original strategy combining state-of-the-art in silico approaches and unique in vivo transgenic mouse models to tackle this challenge specifically for KCs, the most abundant macrophage in the body.

Thus, this proposal aims to:

  1. Determine the TxFs through which the niche imprints the KC identity
  2. Map the Liver-Niche-KC crosstalk during KC development
  3. Identify which liver niche factors influence KC development and function