Defining the Identity and Dynamics of Adult Gastric Isthmus Stem Cells

Abstract

The gastric corpus epithelium is the thickest part of the gastro-intestinal tract and is characterized by rapid tissue turnover. Several markers have been proposed for gastric corpus stem cells in both isthmus and base regions. However, the identity of isthmus stem cells (IsthSCs) and the interaction between distinct stem cell populations is still under debate. Here, based on unbiased genetic labeling and biophysical modeling, we show that corpus glands are compartmentalized into two independent zones, with actively-cycling stem cells maintaining the pit-isthmus-neck region and slow-cycling reserve stem cells maintaining the base. Independent lineage tracing based on Stmn1 and Ki67 expression confirmed that rapidly-cycling IsthSCs maintain the pit-isthmus-neck of corpus glands. Finally, single cell RNA-seq analysis is used to define the molecular identity and lineage relationship of a single, cycling IsthSC population. These observations define the identity and functional behavior of a single population of actively-cycling IsthSCs.