Biology subjects

Gospocic, J.

Publications and source records attributed to Gospocic, J..

4 recordsLinked to original sources

bioRxiv2022

Hormonal gatekeeping via the blood brain barrier governs behavior

Here we reveal an unanticipated role of the blood-brain-barrier (BBB) in regulating complex social behavior in ants. Using scRNA-seq we find localization in the BBB of a key hormone-degrading enzyme called Juvenile hormone esterase (Jhe), and we show that this localization governs the level of Juvenile Hormone (JH3) entering the brain. Manipulation of the Jhe level reprograms the brain transcriptome between ant castes. While ant Jhe is retained and functions intracellularly within the BBB, we show that Drosophila Jhe is naturally extracellular. Heterologous expression of ant Jhe into the Drosophila BBB alters behavior in fly to mimic what is seen in ant. Most strikingly, manipulation of Jhe levels in ant reprograms complex behavior between worker castes. Our study thus uncovers a novel, potentially conserved role of the BBB serving as a molecular gatekeeper for a neurohormonal pathway that regulates social behavior.

neuroscience↗

bioRxiv2022

Long lifespan is maintained by a unique Heat Shock Factor in reproductive ants

Among eusocial insects, reproductive females show longer lifespan than non-reproductive female workers despite high genetic similarity. Using an ant species (Harpegnathos saltator, Hsal) featuring inducible worker reproduction and correlated extended lifespan, we find that long-lived reproductive individuals (called "gamergates") show elevated expression of heat shock response (HSR) genes specifically in the absence of heat stress. This HSR gene elevation is driven in part by gamergate-specific constitutive upregulation of a heat shock transcription factor gene most similar to mammalian HSF2 (called hsalHSF2). In sterile workers hsalHSF2 is bound to DNA only upon heat stress, but in gamergates hsalHSF2 binds to DNA in the absence of heat stress, and correlates with caste-biased gene expression of a subset of heat-inducible genes, thus showing natural bias to gamergates. Remarkably, ectopic expression in D. melanogaster of hsalHSF2 leads to enhanced survival compared to hsalHSF1 following heat stress, as well as extended lifespan. Molecular characterization of these longer-lived flies illustrates multiple parallels between long-lived flies and gamergates, underscoring the centrality of hsalHSF2 to extended lifespan in gamergates. Hence, ant caste-specific heat stress resilience and excessive longevity is, remarkably, transferrable to flies via a specialized ant heat shock factor, HSF2. These findings reinforce the critical role of proteostasis to health and to aging, and reveal novel mechanisms underlying facultative lifespan extension.

genomics↗

bioRxiv2019

Social reprogramming in ants induces longevity-associated glia remodeling

Healthy brain aging is of crucial societal importance; however, the mechanisms that regulate it are largely unknown. Social insects are an outstanding model to study the impact of environment and epigenetics on brain function and aging because workers and queens arise from the same genome but display profound differences in behavior and longevity. In Harpegnathos saltator ants, adult workers can transition to a queen-like phenotypic state called gamergate. This caste transition results in reprogramming of social behavior and lifespan extension. Whether these changes in brain function and physiology cause brain remodeling at the cellular level is not known. Using single-cell RNA-sequencing of Harpegnathos brains undergoing caste transition, we uncovered shifts in neuronal and glial populations. In particular, the conversion of workers into long-lived gamergates caused the expansion of ensheathing glia, which maintain brain health by phagocytosing damaged neuronal structures. These glia cells were lost during aging in normal workers but not in longer-lived gamergates. We observed similar caste- and age-associated differences in ensheathing glia in other Hymenoptera as well as Drosophila melanogaster. We propose that enhanced glia-based neuroprotection promotes healthy brain aging and contributes to the extended lifespan of the reproductive caste in social insects.

neuroscience↗

bioRxiv2017

A Comparison Between Single Cell RNA Sequencing And Single Molecule RNA FISH For Rare Cell Analysis

The development of single cell RNA sequencing technologies has emerged as a powerful means of profiling the transcriptional behavior of single cells, leveraging the breadth of sequencing measurements to make inferences about cell type. However, there is still little understanding of how well these methods perform at measuring single cell variability for small sets of genes and what \"transcriptome coverage\" (e.g. genes detected per cell) is needed for accurate measurements. Here, we use single molecule RNA FISH measurements of 26 genes in thousands of melanoma cells to provide an independent reference dataset to assess the performance of the DropSeq and Fluidigm single cell RNA sequencing platforms. We quantified the Gini coefficient, a measure of rare-cell expression variability, and find that the correspondence between RNA FISH and single cell RNA sequencing for Gini, unlike for mean, increases markedly with per-cell library complexity up to a threshold of [~]2000 genes detected. A similar complexity threshold also allows for robust assignment of multi-genic cell states such as cell cycle phase. Our results provide guidelines for selecting sequencing depth and complexity thresholds for single cell RNA sequencing. More generally, our results suggest that if the number of genes whose expression levels are required to answer any given biological question is small, then greater transcriptome complexity per cell is likely more important than obtaining very large numbers of cells.

genomics↗