Molecular and Functional Characterization of Human Intestinal Organoids and Monolayers for Modeling Epithelial Barrier

Patient-derived organoid models can transform drug discovery for inflammatory bowel disease, but differentiation and functional characterization inconsistencies limit that transformation. Jelinsky et al. profiled molecular and cellular features across a range of intestinal organoid models using bulk RNA sequencing, among other technologies, and examined differentiation and establishing a functional epithelial barrier.

Exposure to the Amino Acids Histidine, Lysine, and Threonine Reduces mTOR Activity and Affects Neurodevelopment in a Human Cerebral Organoid Model

The authors pioneered the use of human cerebral organoids to investigate the impact of amino acid supplementation on neurodevelopment. RNA sequencing identified gene expression changes after supplementation, with enrichment in genes related to mTOR signaling and immune function, a.o., and to specific cell types, including proliferative precursor cells, microglia, and astrocytes.

BMP gradient along the intestinal villus axis controls zonated enterocyte and goblet cell states

Beumer et al. show that the bone morphogenetic protein (BMP) signaling pathway controls the creation of functional zones along the crypt-villus axis. A gene lipid uptake gene signature is enriched in the villus tip and could be therapeutically exploited with BMP inhibitors.

Identification of Enteroendocrine Regulators by Real-Time Single-Cell Differentiation Mapping

This paper presents Neurog3Chrono, a bi-fluorescent reporter for the differentiation process of enteroendocrine cells, the intestines’ hormone-excreting cells. It measures fluorescence in time and per cell, enabling the real-time arrangement of single-cell gene expression profiles.