Induction of different human enteroendocrine cells in intestinal organoids

<title>Abstract</title> Intestinal enteroendocrine cells \(EECs) are key players in mammalian physiology as largest endocrine organ, and regulate metabolic processes such as insulin secretion and induction of satiety. EECs are rare cell types \(less than 1% of the epithelium) and produce a large number of different hormones making these challenging to study. Model systems to assess the differentiation and function of these essential cell types have been lacking. In a novel approach, we describe the induction of human EECs in intestinal organoids. Moreover, in the manuscript linked to this protocol, we describe that manipulating the BMP signaling pathway allows to induce expression of specific sets of hormones that correspond to the EEC state in the crypt-villus axis. This differentiation platform can be used to study the function of EECs and could contribute to the development of drugs for diabetes and obesity.