Here, we address these questions in the context of the intestinal epithelium, an ideal model for continuously renewing tissue ( Beumer and Clevers, 2016 Cheng and Leblond, 1974a Tian et al., 2016).
What are the tissue-wide effects of common microenvironmental signals on cell type composition? How do multiple signals modify each other’s effects? Finally, are there intrinsic tissue properties that shape response to diverse signals? Further, most studies focus on the effects of individual signals on individual cell types, due to a lack of methods that enable systematic identification of signal integration mechanisms. Dissection of mechanisms underlying the mapping from signals to tissue composition is complicated by the heterogeneous makeup of interconnected cell types, which exert influences upon one another through lineage structure and cell-cell interactions.
A central question in the study of complex tissues is how diverse signals are integrated to regulate cell type composition.
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