Person:

Herbst, Rebecca

Background: The merging of genomes in inter-specific hybrids can result in novel phenotypes, including increased growth rate and biomass yield, a phenomenon known as heterosis. Heterosis is typically viewed as the opposite of hybrid incompatibility. In this view, the superior performance of the hybrid is attributed to heterozygote combinations that compensate for deleterious mutations accumulating in each individual genome, or lead to new, over-dominating interactions with improved performance. Still, only fragmented knowledge is available on genes and processes contributing to heterosis. Results: We describe a budding yeast hybrid that grows faster than both its parents under different environments. Phenotypically, the hybrid progresses more rapidly through cell cycle checkpoints, relieves the repression of respiration in fast growing conditions, does not slow down its growth when presented with ethanol stress, and shows increased signs of DNA damage. A systematic genetic screen identified hundreds of S. cerevisiae alleles whose deletion reduced growth of the hybrid. These growth-affecting alleles were condition-dependent, and differed greatly from alleles that reduced the growth of the S. cerevisiae parent. Conclusions: Our results define a budding yeast hybrid that is perturbed in multiple regulatory processes but still shows a clear growth heterosis. We propose that heterosis results from incompatibilities that perturb regulatory mechanisms, which evolved to protect cells against damage or prepare them for future challenges by limiting cell growth. Electronic supplementary material The online version of this article (doi:10.1186/s12915-017-0373-7) contains supplementary material, which is available to authorized users.

Intestinal epithelial cells (IECs) absorb nutrients, respond to microbes, provide barrier function and help coordinate immune responses. We profiled 53,193 individual epithelial cells from mouse small intestine and organoids, and characterized novel subtypes and their gene signatures. We showed unexpected diversity of hormone-secreting enteroendocrine cells and constructed their novel taxonomy. We distinguished between two tuft cell subtypes, one of which expresses the epithelial cytokine TSLP and CD45 (Ptprc), the pan-immune marker not previously associated with non-hematopoietic cells. We also characterized how cell-intrinsic states and cell proportions respond to bacterial and helminth infections. Salmonella infection caused an increase in Paneth cells and enterocytes abundance, and broad activation of an antimicrobial program. In contrast, Heligmosomoides polygyrus caused an expansion of goblet and tuft cell populations. Our survey highlights new markers and programs, associates sensory molecules to cell types, and uncovers principles of gut homeostasis and response to pathogens.