The different cell types of the human gut develop from stem cells through a process of differentiation. Researchers from the Organoid group (Hubrecht Institute), together with researchers at the Princess Máxima Center and Maastricht University, used gut organoids to perform a systematic CRISPR screening of 1800 human transcription factors and identified ZNF800 as a key regulator of the differentiation of a specific gut cell type, the enteroendocrine cells. The results of the study were published in Science on 26 October 2023 and could have implications for our understanding of gastrointestinal diseases and endocrine disorders, as well as pancreatic development and diabetes.
The human gut contains various cell types, each with specific functions. These cell types all arise from the stem cells of the gut: cells that are not specialized yet, but have the potential to become functionally specialized cells. Important cell types of the gut are enterocytes, responsible for the absorption of nutrients, goblet cells, which produce mucus, Paneth cells, which secrete antimicrobial peptides, and enteroendocrine cells (EECs), which produce various hormones. The hormones produced by the EECs regulate digestive processes, such as nutrient absorption, appetite and glucose metabolism. In this study, researchers from the Organoid group investigated how stem cells become EECs through a process called differentiation. For this they used gut organoids: lab-grown miniature organs that mimic the structure and function of the actual gut.