Mammals have forged an evolutionary alliance with commensal microbes that harmoniously live on barrier surfaces and have profound effects on host health and disease. Despite their residence on epithelial barriers, surprisingly little is known about how commensals influence epithelial stem cells (EpSCs), which continuously maintain epithelia throughout our lifetime. By taking cues from their microenvironment or “niche”, EpSCs balance self-renewal and differentiation to generate tissues. Using the skin epithelium as a model system, here we ask: Are commensal microbes an EpSC niche component? And how do EpSCs remember their history of commensal colonization? We propose to experimentally manipulate both host and microbe to understand the mechanisms and consequences of their crosstalk. Thus, these studies will lay the foundational groundwork for the broader understanding of how our microbial partners influence EpSCs and consequently epithelial tissue fitness and function.

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