Stanford Advisors

All Publications

  • Self-sperm induce resistance to the detrimental effects of sexual encounters with males in hermaphroditic nematodes. eLife Booth, L. N., Maures, T. J., Yeo, R. W., Tantilert, C., Brunet, A. 2019; 8


    Sexual interactions have a potent influence on health in several species, including mammals. Previous work in C. elegans identified strategies used by males to accelerate the demise of the opposite sex (hermaphrodites). But whether hermaphrodites evolved counter-strategies against males remains unknown. Here we discover that young C. elegans hermaphrodites are remarkably resistant to brief sexual encounters with males, whereas older hermaphrodites succumb prematurely. Surprisingly, it is not their youthfulness that protects young hermaphrodites, but the fact that they have self-sperm. The beneficial effect of self-sperm is mediated by a sperm-sensing pathway acting on the soma rather than by fertilization. Activation of this pathway in females triggers protection from the negative impact of males. Interestingly, the role of self-sperm in protecting against the detrimental effects of males evolved independently in hermaphroditic nematodes. Endogenous strategies to delay the negative effect of mating may represent a key evolutionary innovation to maximize reproductive success.

    View details for DOI 10.7554/eLife.46418

    View details for PubMedID 31282863

  • Lysosome activation clears aggregates and enhances quiescent neural stem cell activation during aging SCIENCE Leeman, D. S., Hebestreit, K., Ruetz, T., Webb, A. E., McKay, A., Pollina, E. A., Dulken, B. W., Zhao, X., Yeo, R. W., Ho, T. T., Mahmoudi, S., Devarajan, K., Passegue, E., Rando, T. A., Frydman, J., Brunet, A. 2018; 359 (6381): 1277–82


    In the adult brain, the neural stem cell (NSC) pool comprises quiescent and activated populations with distinct roles. Transcriptomic analysis revealed that quiescent and activated NSCs exhibited differences in their protein homeostasis network. Whereas activated NSCs had active proteasomes, quiescent NSCs contained large lysosomes. Quiescent NSCs from young mice accumulated protein aggregates, and many of these aggregates were stored in large lysosomes. Perturbation of lysosomal activity in quiescent NSCs affected protein-aggregate accumulation and the ability of quiescent NSCs to activate. During aging, quiescent NSCs displayed defects in their lysosomes, increased accumulation of protein aggregates, and reduced ability to activate. Enhancement of the lysosome pathway in old quiescent NSCs cleared protein aggregates and ameliorated the ability of quiescent NSCs to activate, allowing them to regain a more youthful state.

    View details for PubMedID 29590078

    View details for PubMedCentralID PMC5915358

  • Chromatin accessibility dynamics reveal novel functional enhancers in C. elegans GENOME RESEARCH Daugherty, A. C., Yeo, R. W., Buenrostro, J. D., Greenleaf, W. J., Kundaje, A., Brunet, A. 2017; 27 (12): 2096–2107


    Chromatin accessibility, a crucial component of genome regulation, has primarily been studied in homogeneous and simple systems, such as isolated cell populations or early-development models. Whether chromatin accessibility can be assessed in complex, dynamic systems in vivo with high sensitivity remains largely unexplored. In this study, we use ATAC-seq to identify chromatin accessibility changes in a whole animal, the model organism Caenorhabditis elegans, from embryogenesis to adulthood. Chromatin accessibility changes between developmental stages are highly reproducible, recapitulate histone modification changes, and reveal key regulatory aspects of the epigenomic landscape throughout organismal development. We find that over 5000 distal noncoding regions exhibit dynamic changes in chromatin accessibility between developmental stages and could thereby represent putative enhancers. When tested in vivo, several of these putative enhancers indeed drive novel cell-type- and temporal-specific patterns of expression. Finally, by integrating transcription factor binding motifs in a machine learning framework, we identify EOR-1 as a unique transcription factor that may regulate chromatin dynamics during development. Our study provides a unique resource for C. elegans, a system in which the prevalence and importance of enhancers remains poorly characterized, and demonstrates the power of using whole organism chromatin accessibility to identify novel regulatory regions in complex systems.

    View details for PubMedID 29141961

  • Deconstructing Dietary Restriction: A Case for Systems Approaches in Aging. Cell metabolism Yeo, R., Brunet, A. 2016; 23 (3): 395-396


    Dietary restriction is a robust and conserved intervention to slow aging and extend lifespan. In this issue of Cell Metabolism, Hou et al. (2016) use a systems biology approach in C. elegans to uncover key molecular nodes underlying the transcriptomic response to dietary restriction and predict novel regulators of lifespan.

    View details for DOI 10.1016/j.cmet.2016.02.018

    View details for PubMedID 26959179

    View details for PubMedCentralID PMC5240043