ABSTRACT
Organoids have been widely used for studying tissue growth and modeling diseases, but achieving physiologically relevant architecture, size, and function has remained a challenge. Here, we develop a next-generation organotypic culture method that enables the formation of a highly patterned, complex, branched tissue that is spatially organized to accurately recapitulate the morphology, scale, cellular, transcriptional, and tissue-level heterogeneity of human breast tissue. Hormone responsiveness of organoids is also a feature allowing for examination of androgen therapy or post-menopausal changes to breast tissue development and regeneration. Live imaging allows for studying stem cell dynamics during organoid formation and is adaptable to a high throughput setting. Real-time imaging of organoid formation reveals activation of latent epithelial organogenesis programs and inductive cellular dynamics that drive formation of a miniature breast tissue along with its mesenchyme akin to tissue stroma. By advancing human breast organoid technology, this model can elucidate cell- and tissue-level consequences to hormonal changes and therapy. In addition, this method can lead to new insights into the cellular, molecular, and tissue-level processes involved in organogenesis and regeneration, as well as disease.
ABSTRACT
Microbes engage in numerous social behaviours that are critical for survival and reproduction, and that require individuals to act as a collective. Various mechanisms ensure that collectives are composed of related, cooperating cells, thus allowing for the evolution and stability of these traits, and for selection to favour traits beneficial to the collective. Since microbes are difficult to observe directly, sociality in natural populations can instead be investigated using evolutionary genetic signatures, as social loci can be evolutionary hotspots. The budding yeast has been studied for over a century, yet little is known about its social behaviour in nature. Flo11 is a highly regulated cell adhesin required for most laboratory social phenotypes; studies suggest it may function in cell recognition and its heterogeneous expression may be adaptive for collectives such as biofilms. We investigated this locus and found positive selection in the areas implicated in cell-cell interaction, suggesting selection for kin discrimination. We also found balancing selection at an upstream activation site, suggesting selection on the level of variegated gene expression. Our results suggest this model yeast is surprisingly social in natural environments and is probably engaging in various forms of sociality. By using genomic data, this research provides a glimpse of otherwise unobservable interactions.
