A single cell survey of the microbial impacts on the mouse small intestinal epithelium.

The small intestinal epithelial barrier inputs signals from the gut microbiota in order to balance physiological inflammation and tolerance, and to promote homeostasis. Understanding the dynamic relationship between microbes and intestinal epithelial cells has been a challenge given the cellular heterogeneity associated with the epithelium and the inherent difficulty of isolating and identifying individual cell types. Here, we used single-cell RNA sequencing of small intestinal epithelial cells from germ-free and specific pathogen-free mice to study microbe-epithelium crosstalk at the single-cell resolution. The presence of microbiota did not impact overall cellular composition of the epithelium, except for an increase in Paneth cell numbers. Contrary to expectations, pattern recognition receptors and their adaptors were not induced by the microbiota but showed concentrated expression in a small proportion of epithelial cell subsets. The presence of the microbiota induced the expression of host defense- and glycosylation-associated genes in distinct epithelial cell compartments. Moreover, the microbiota altered the metabolic gene expression profile of epithelial cells, consequently inducing mTOR signaling thereby suggesting microbe-derived metabolites directly activate and regulate mTOR signaling. Altogether, these findings present a resource of the homeostatic transcriptional and cellular impact of the microbiota on the small intestinal epithelium.

Defined mouse microbiota: An "evolving" tool.

In this issue of Cell Host & Microbe, Yilmaz et al. carried out one of the longest reported in vivo microbiota evolution studies to demonstrate ongoing positive selection of a bacterial consortium within the murine gut. Their findings have important implications for the development of gnotobiotic mouse models.

Defined gut microbial communities: promising tools to understand and combat disease.

Defined gut microbial communities are emerging tools that allow detailed studies of microbial ecosystems and their interactions with the host. In this article, we review strategies underlying the design of defined consortia and summarize the efforts to introduce simplified communities into in vitro and in vivo models. We conclude by highlighting the potential of defined microbial ecosystems as effective modulation strategies for health benefits.

Progesterone receptor membrane component 1 is phosphorylated upon progestin treatment in breast cancer cells.

Menopausal hormone therapy, using estrogen and synthetic progestins, is associated with an increased risk of developing breast cancer. The effect of progestins on breast cells is complex and not yet fully understood. In previous in vitro and in vivo studies, we found different progestins to increase the proliferation of Progesterone Receptor Membrane Component-1 (PGRMC1)-overexpressing MCF7 cells (MCF7/PGRMC1), suggesting a possible role of PGRMC1 in transducing membrane-initiated progestin signals. Understanding the activation mechanism of PGRMC1 by progestins will provide deeper insights into the mode of action of progestins on breast cells and the often-reported phenomenon of elevated breast cancer rates upon progestin-based hormone therapy. In the present study, we aimed to further investigate the effect of progestins on receptor activation in MCF7 and T47D breast cancer cell lines. We report that treatment of both breast cancer cell lines with the progestin norethisterone (NET) induces phosphorylation of PGRMC1 at the Casein Kinase 2 (CK2) phosphorylation site Ser181, which can be decreased by treatment with CK2 inhibitor quinalizarin. Point mutation of the Ser181 phosphorylation site in MCF7/PGRMC1 cells impaired proliferation upon NET treatment. This study gives further insights into the mechanism of differential phosphorylation of the receptor and confirms our earlier hypothesis that phosphorylation of the CK2-binding site is essential for activation of PGRMC1. It further suggests an important role of PGRMC1 in the tumorigenesis and progression of breast cancer in progestin-based hormone replacement therapy.