TY - JOUR T1 - Maturation of human intestinal epithelium from pluripotency <em>in vitro</em> JF - bioRxiv DO - 10.1101/2021.09.24.460132 SP - 2021.09.24.460132 AU - Umut Kilik AU - Qianhui Yu AU - Rene Holtackers AU - Makiko Seimiya AU - Aline Xavier da Silveira dos Santos AU - Barbara Treutlein AU - Jason R. Spence AU - J. Gray Camp Y1 - 2021/01/01 UR - http://biorxiv.org/content/early/2021/09/24/2021.09.24.460132.abstract N2 - Methods to generate human intestinal tissue from pluripotent stem cells (PSCs) open new inroads into modeling intestine development and disease. However, current protocols require organoid transplantation into an immunocompromised mouse to achieve matured and differentiated epithelial cell states. Inspired by developmental reconstructions from primary tissues, we establish a regimen of inductive cues that enable stem cell maturation and epithelial differentiation entirely in vitro. We show that the niche factor Neuregulin1 (NRG1) promotes morphological change from proliferative epithelial cysts to matured epithelial tissue in three-dimensional cultures. Single-cell transcriptome analyses reveal differentiated epithelial cell populations, including diverse secretory and absorptive lineages. Comparison to multi-organ developmental and adult intestinal cell atlases confirm the specificity and maturation state of cell populations. Altogether, this work opens a new direction to use in vitro matured epithelium from human PSCs to study human intestinal epithelium development, disease, and evolution in controlled culture environments.Competing Interest StatementThe authors have declared no competing interest. ER -