Biology subjects

Yeo, R. W.

Publications and source records attributed to Yeo, R. W..

2 recordsLinked to original sources

bioRxiv2021

Chromatin accessibility dynamics of neurogenic niche cells reveal a reversible decline in neural stem cell migration during aging

Aging is accompanied by a deterioration in the regenerative and repair potential of stem cell niches in the brain1-5. However, the mechanisms underlying this decline are largely unknown. Here we characterize genome-wide chromatin accessibility in young and old neurogenic niche cells in vivo, revealing defects in neural stem cell (NSC) adhesion and migration during aging. Interestingly, chromatin accessibility at cell adhesion and migration genes decreases with age in quiescent NSCs but increases with age in activated (proliferative) NSCs, and this is accompanied by corresponding expression changes in these genes. We experimentally validate that quiescent and activated NSCs exhibit opposing adhesion and migration behaviors with age: quiescent NSCs become less adhesive (and more migratory) whereas activated NSCs and progeny become more adhesive (and less migratory) during aging. We also show that the ability of activated NSCs and progeny to mobilize out of the niche during in vivo neurogenesis diminishes during aging. Using tension sensors with single molecule resolution, we find that one of the cellular mechanisms by which aging impairs the migration of old activated NSCs and progeny involves increased force-producing adhesions. We identify inhibition of the cytoskeletal-regulating kinase ROCK6, 7 as a way to reduce force-producing adhesions and restore migration in old activated NSCs in vitro. Interestingly, inhibition of ROCK in the neurogenic niche of old mice boosts neurogenesis to the olfactory bulb in vivo. These results have important implications for restoring the migratory potential of NSCs and progeny and for improving neurogenesis in the aged brain.

neuroscience↗

bioRxiv2020

Males deploy multifaceted strategies and hijack longevity pathways to induce premature demise of the opposite sex

Interactions between the sexes negatively impact health in many species, including mammals1–9. In mice, sexual interactions induce weight gain and shorten lifespan in females, independent of fertilization6,9. In Caenorhabditis, males shorten the lifespan of the opposite sex (females or hermaphrodites)1–3,8. However, the mechanisms underlying the negative influence of males on lifespan – and their overlap with known longevity pathways – are still largely unknown. Here, we use transcriptomic profiling and targeted screens to systematically uncover new conserved genes involved in male-induced demise. Interestingly, deficiency of these genes individually, and especially in combination, induces strong protection, highlighting the benefit of combining interventions to extend lifespan. Some genes (e.g. acbp-3, col-43) only extend hermaphrodite lifespan when knocked-down in the presence of males, suggesting specific protective mechanisms against male-induced demise. However, we also uncover two previously unknown longevity genes (sri-40 and delm-2) that, when knocked-down, extend hermaphrodite lifespan both with and without males, which points to new broad mechanisms of resistance. In sharp contrast, many classical long-lived mutants are actually short-lived in the presence of males, suggesting that males hijack and suppress known longevity pathways. This systematic analysis reveals striking differences in longevity in single sex versus mixed sex environments and uncovers the elaborate network of functional regulation elicited by sexual interactions, which could extend to other species.Competing Interest StatementThe authors have declared no competing interest.View Full Text

genetics↗