Preclinical studies in animal models, including intra-vital imaging, transcriptome profiling, as well as Cre recombinase-mediated fate mapping and conditional mutagenesis, have provided critical insights into the origins and functions of microglia. Like other tissue-resident macrophages (TRM), microglia are first established from primitive progenitors originating in the yolk sac (YS). While most embryonic TRM (eTRM) are replaced shortly after birth by monocyte-derived TRM (moTRM) cells originating from fetal or, later on, by adult monocytes, YS-derived microglia (YSMg) is considered to persist. What provides YSMg with a competitive advantage over monocyte-derived microglia (MoMg) remains, however, unclear. Indeed, we recently discovered that selected CNS regions are in aging mice seeded with MoMg 1 - a notion also corroborated by emerging human data 2,3. Our studies in the SPP 2395 consortium aim to decipher the interplay of YSMg and MoMg during aging, with a particular emphasis on Csf1 / Csf1r interactions that are also relevant for CSF1R-associated leukoencephalopathy studied by our collaborator C Bergner (Project 2) 4. Moreover, with a focus on their failure to secrete IL-10, we try, as a follow-up to our recent work 5, to understand what makes Mg so unique among TRM.

1. Kim, J.-S. et al. (2025). Cell Rep. https://doi.org/10.1016/j.celrep.2025.115609.
2. Bouzid, H. et al. (2023). Nat. Med.,. https://doi.org/10.1038/s41591-023-02397-2.
3. Huang, A.Y. et al. (2026). Cell, https://doi.org/10.1016/j.cell.2026.03.040.
4. Bergner, C.G., et al. (2023). Front. Neurol. https://doi.org/10.3389/fneur.2023.1163107.
5. Shemer, A., et al. (2020). Immunity https://doi.org/10.1016/j.immuni.2020.09.018.