Novel lentiviral constructs for the specification of rare and ectopic cell types in human colonoids

In the past 15 years, organoid models have revolutionized the study of the human gastrointestinal (GI) epithelium. Organoids can be derived from patient tissue and grown as strictly epithelial structures referred to as enteroids and colonoids. Despite their utility, rare cell types are often absent in enteroids and colonoids. We hypothesized that induced expression of key transcription factors (TFs) would be sufficient to specify a subset of these cell types. To test this hypothesis, we generated lentiviral constructs that allow the inducible expression of cell-type specifying TFs. We transduced human enteroids and colonoids with these constructs and examined their ability to induce differentiated cell types.