Huhn, S. | bioRxiv Science

bioRxiv2020

Innate immune signalling drives loser cell elimination during stem cell competition in the Drosophila testis

In the Drosophila testis, a group of stromal cells termed hub provides multiple niche signals for the surrounding germline and somatic stem cells. Stem cells of both populations compete for physical retention in the niche, and stem cell clones unable to transduce any one niche signal are rapidly eliminated by differentiation. We have recently mapped the transcriptomes of isolated somatic cyst stem cells and differentiated cyst cells, and found that the stem cells but not their differentiated progeny activate an immune response involving the NF-{kappa}B transcription factor Relish (Rel). Here we show i) that Rel activation is not required for stemness but occurs physiologically in "losers" of stem cell competition, ii) that loss of Rel or the upstream receptor Toll suppresses loser elimination irrespective of how loser fate was induced, and iii) that clonal Rel activation is sufficient for the displacent of neutral or winner cells from the niche, even if the winners otherwise retain stem cell properties. This generalized mechanism for the elimination of "loser" stem cells may mask the compound nature of stem cell behaviour, and instead generate the impression of a binary cell fate decision between stemness and differentiation.

developmental biology↗

bioRxiv2019

Differences in intake of high-fat high-sugar diet are related to variations in central dopamine in humans.

Obesity is associated with alterations in dopaminergic transmission and cognitive function. Recent findings from rodent studies suggest that diets rich in saturated fat and refined sugars (HFS) induce changes in the dopamine system independent of excessive body weight. However, so far the impact of HFS on the human brain has not been investigated. Here, we compared the effect of dietary dopamine depletion on dopamine dependent cognitive tasks between two groups that differ in habitual intake of dietary fat and sugar. Specifically, we used a double-blind within-subject crossover design to compare the effect of acute phenylalanine/tyrosine depletion (APTD) on a reinforcement learning and a working memory task, in two groups that are on opposite ends of the spectrum of self-reported HFS intake (low vs. high intake: LFS vs. HFS group). We tested 31 healthy young women, who were matched for BMI (mostly normal weight to overweight) and IQ. Depletion of central dopamine reduced the working memory specific performance on the operation span task (OSPAN) in the LFS, but not in the HFS group (p = 0.023, r = 0.210). Learning from positive and negative reinforcement (probabilistic selection task: PST) was increased in both diet groups after dopamine depletion (p = 0.048, r = 0.144). As secondary exploratory research question we measured peripheral dopamine precursor availability (pDAP) at baseline as an estimate for central dopamine levels. The HFS group had a significantly higher pDAP at baseline compared to the LFS group (p = .048, r = -0.355). Our data provides first evidence that the intake of HFS is associated with changes in indirect measures of central dopamine levels in humans. The observed associations are independent of body weight status, suggesting that consumption of HFS might be associated with maladaptive behaviors contributing to the development of obesity.

neuroscience↗