Engelhardt, E. | bioRxiv Science

bioRxiv2024

The host genotype actively shapes its microbiome across generations

BackgroundThe microbiome greatly affects health and wellbeing. Evolutionarily, it is doubtful that a host would rely on chance alone to pass on microbial colonization to its offspring. However, the literature currently offers only limited evidence regarding two alternative hypotheses: active microbial shaping by host genetic factors or transmission of a microbial maternal legacy. ResultsTo further dissect the influence of host genetics and maternal inheritance, we collected 2-cell stage embryos from two representative wildtypes, C57BL6/J and BALB/c, and transferred a mixture of both genotype embryos into hybrid recipient mice to be inoculated by an identical microbiome at birth. ConclusionsObserving the offspring for six generations unequivocally emphasizes the impact of host genetic factors over maternal legacy in constant environments, akin to murine laboratory experiments. Interestingly, maternal legacy solely controlled the microbiome in the first offspring generation. However, current evidence supporting maternal legacy has not extended beyond this initial generation, resolving the aforementioned debate. O_FIG O_LINKSMALLFIG WIDTH=197 HEIGHT=200 SRC="FIGDIR/small/584950v2_ufig1.gif" ALT="Figure 5"> View larger version (48K): org.highwire.dtl.DTLVardef@790822org.highwire.dtl.DTLVardef@4f486org.highwire.dtl.DTLVardef@151ab46org.highwire.dtl.DTLVardef@c3ab66_HPS_FORMAT_FIGEXP M_FIG graphical abstract C_FIG

ecology↗

bioRxiv2019

Mitochondrial fusion in reactive astrocytes coordinates local metabolic domains to promote vascular repair

Astrocytes have emerged for playing important roles in brain tissue repair, however the underlying mechanisms remain poorly understood. We show that acute injury and blood-brain barrier disruption trigger the formation of a prominent mitochondrial-enriched compartment in astrocytic end-feet which enables vascular remodeling. Integrated imaging approaches revealed that this mitochondrial clustering is part of an adaptive response regulated by fusion dynamics. Astrocyte-specific conditional deletion of Mitofusin 2 (Mfn2) suppressed perivascular mitochondrial clustering and disrupted mitochondria-ER contact sites. Functionally, two-photon imaging experiments showed that these structural changes were mirrored by impaired mitochondrial Ca2+ uptake leading to abnormal cytosolic transients within end-feet in vivo. At the tissue level, a compromised vascular complexity in the lesioned area was restored by boosting mitochondrial-ER perivascular tethering in MFN2-deficient astrocytes. These data unmask a crucial role for mitochondrial dynamics in coordinating astrocytic local domains and have important implications for repairing the injured brain.

cell biology↗