Biology subjects

Doetsch, F.

Publications and source records attributed to Doetsch, F..

6 recordsLinked to original sources

bioRxiv2026

The brain-meningeal interface functions as a reservoir and entry site for brain parenchymal macrophages

Microglia are regarded as self-maintaining brain parenchymal macrophages without contribution from adult hematopoiesis. Nevertheless, peripheral macrophage engraftment into the brain has been reported, but the biological variables governing central nervous system (CNS) macrophage niche access remain unclear. We show that CNS macrophage engraftment is determined by the balance between tissue-resident macrophage (TRM) self-renewal and the temporal alignment of niche opening with the availability of engraftment-competent cells and proximity to the vacated niche, rather than prolonged niche vacancy. Fate mapping revealed that monocytes entering the subdural space undergo border-associated macrophage (BAM)-like differentiation, clonal expansion, and transpial migration into the parenchyma, whereas mature BAMs directly repopulate selectively vacated parenchymal niches. We further identify a parenchymal macrophage population with a peripheral BAM-like transcriptional program in aged and neurodegenerative human brains, challenging the dogma of MG-exclusivity. Together, these findings establish a predictive framework for interpreting macrophage maintenance and replacement and for developing macrophage-based therapies.

neuroscience↗

bioRxiv2025

Choroid plexus sex differences in secretory signalling and immune compartments

The choroid plexus (ChP)-cerebrospinal fluid (CSF) axis is emerging as a key regulator of the brain environment. The ChP is a multi-functional structure, which forms the blood-CSF barrier, and acts as a sensor of inputs from the periphery and the brain, dynamically responding by modulating its secretome into the CSF. However, sex differences in the ChP have been little explored. Molecular profiling of the adult mouse ChP at the transcriptomic and proteomic levels revealed sex differences across multiple cell types, with immune signatures enriched in females. Interestingly, border associated macrophages showed distinct sex differences in the stromal and epiplexus compartments. We further uncovered sex differences in ChP secretory signalling, with functional differences between males and females. Finally, the human LVChP showed largely similar sex differences. Together, our findings highlight that sex differences may play an important role in ChP function in both health and disease.

neuroscience↗

bioRxiv2022

A fluorescent perilipin 2 knock-in mouse model visualizes lipid droplets in the developing and adult brain

Lipid droplets (LDs) are dynamic lipid storage organelles. They are tightly linked to metabolism and can exert protective functions, making them important players in health and disease. Most LD studies in vivo rely on staining methods, providing only a snapshot. We therefore developed a LD-reporter mouse by endogenously labelling the LD coat protein perilipin 2 (PLIN2) with tdTomato, enabling staining-free fluorescent LD visualisation in living and fixed tissues and cells. Here we validate this model under standard and high-fat diet conditions and demonstrate that LDs are present in various cells in the healthy brain, including neurons, astrocytes, ependymal cells, neural stem/progenitor cells and microglia. Furthermore, we show that LDs are abundant during brain development and can be visualized using live-imaging of embryonic slices. Taken together, our tdTom-Plin2 mouse serves as a novel tool to study LDs and their dynamics under both physiological and diseased conditions in all tissues expressing Plin2.

cell biology↗

bioRxiv2021

miR-17~92 exerts stage-specific effects in adult V-SVZ neural stem cell lineages

In the adult mouse brain, neural stem cells (NSCs) in the ventricular-subventricular zone (V-SVZ) generate neurons and glia throughout life. microRNAs are important regulators of cell states, frequently acting in a stage- or context-dependent manner. Here, miRNA profiling of FACS-purified populations identified miR-17[~]92 as highly upregulated in activated NSCs and transit amplifying cells (TACs) in comparison to quiescent NSCs. Conditional deletion of miR-17[~]92 in NSCs reduced stem cell proliferation both in vitro and in vivo. In contrast, in TACs, miR-17[~]92 deletion caused a selective shift from neurogenic DLX2+ TACs towards oligodendrogenic OLIG2+ TACs, resulting in increased oligodendrogenesis to the corpus callosum. miR-17[~]92 deletion also decreased proliferation and maturation of intraventricular oligodendrocyte progenitor cells. Together, these findings reveal stage- and cell-type-specific functions of the miR-17[~]92 cluster within adult V-SVZ neural stem cell lineages.

neuroscience↗

bioRxiv2021

Spatio-Temporal Recruitment Of Adult Neural Stem Cells For Transient Neurogenesis During Pregnancy

Neural stem cells (NSCs) in the adult mouse brain contribute to lifelong brain plasticity. NSCs in the adult ventricular-subventricular zone (V-SVZ) are heterogeneous and, depending on their location in the niche, give rise to different subtypes of olfactory bulb interneurons. Here, we show that during pregnancy multiple regionally-distinct NSCs are dynamically recruited at different times. Coordinated temporal activation of these NSC pools generates sequential waves of short-lived olfactory bulb interneuron subtypes that mature in the mother around birth and in the perinatal care period. Concomitant with neuronal addition, oligodendrocyte progenitors also transiently increase in the olfactory bulb. Thus, life experiences, such as pregnancy, can trigger transient neurogenesis and gliogenesis under tight spatial and temporal control, and may provide a novel substrate for brain plasticity in anticipation of temporary physiological demand.

neuroscience↗

bioRxiv2019

Release of stem cells from quiescence reveals multiple gliogenic domains in the adult brain

Quiescent neural stem cells (NSCs) in the adult ventricular-subventricular zone (V-SVZ) have a regional identity and undergo activation to generate neurons. The domains for gliogenesis are less explored. Here we show that Platelet-Derived Growth Factor Receptor beta (PDGFR{beta}) is expressed by adult V-SVZ NSCs that generate olfactory bulb interneurons and glia with slow baseline kinetics. Selective deletion of PDGFR{beta} in adult V-SVZ NSCs leads to their release from quiescence uncovering multiple domains in the septal wall for oligodendrocyte and astrocyte formation. Unexpectedly, we identify a novel intraventricular oligodendrocyte progenitor inside the brain ventricles. Together our findings reveal different NSC spatial domains for gliogenesis in the adult V-SVZ that are largely quiescent under homeostasis and may have key functions for brain plasticity.

neuroscience↗