Endocrine Abstracts

The intestinal epithelium (IE) is populated by different cell types each with a unique set of functions. Each cell type is derived from a common progenitor, the stem cell. The hierarchy of epithelial cell fate is transcriptionally regulated for example, Notch signalling defines secretory versus absorptive destiny. Peptide hormone producing enteroendocrine (EE) cells are scattered throughout the epithelium where they integrate complex nutrient signals and respond by promoting metabolic equilibrium. Understanding EE cell fate in health and disease could identify novel targets for the treatment of metabolic and other gut related endocrine diseases. EE progenitor cells are defined by the expression of Neurogenin3 (Ngn3), a transcription factor of the bHLH family, from which all mature enteroendocrine cells are thought to descend. However, the concrete signalling pathways that defines the terminal differentiation of different EEC cell types is poorly understood. This exposes a knowledge gap of the intestinal epithelium dynamics and consequently, progenitor cell differentiation and fate. We sought to scrutinise the cell fate of enteroendocrine progenitor cells using Ngn3-Cre-RFP mouse small intestine organoids. Ngn3+ red fluorescent cells were separated from the negative population by fluorescence-activated cell sorting (FACS) and gene expression in both populations quantified using qPCR. As expected, Ngn3+ population was significantly enriched for the EE transcription factor Ngn3 (P<0.01) as well as the pan-enteroendocrine marker, Chromogranin A (P<0.01). Surprisingly, expression of Paneth cell marker, Lysozyme (P<0.001) and Goblet cell marker, Mucin2 (P<0.01) were also significantly augmented in Ngn3+ cells. Our data suggest that EE progenitors contribute more extensively to the different intestinal epithelial cell populations than previously identified. Given the role of secretory cells (Paneth, goblet and EE cells) in gastrointestinal-related diseases, defining intestinal epithelium cell fate decisions could help to delineate novel therapeutic paths for gastrointestinal disorders.