Defining the Identity and Dynamics of Adult Gastric Isthmus Stem Cells

Summary The gastric corpus epithelium is the thickest part of the gastrointestinal tract and is rapidly turned over. 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 slow-cycling stem cells maintaining the base and actively cycling stem cells maintaining the pit-isthmus-neck region through a process of “punctuated” neutral drift dynamics. Independent lineage tracing based on Stmn1 and Ki67 expression confirmed that rapidly cycling IsthSCs maintain the pit-isthmus-neck region. Finally, single-cell RNA sequencing (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 IsthSCs.
Graphical Abstract
Highlights • Marker-free lineage tracing reveals two types of stem cells in the gastric corpus • Actively cycling isthmus stem cells follow “punctuated” neutral drift dynamics • Stmn1 and Ki67 lineage tracing confirms the active cycling of isthmus stem cells • Single-cell RNA-seq defines identity and lineage relationship of isthmus stem cells
Using lineage-tracing assays and single-cell gene expression profiling, Han et al. show that the mouse gastric corpus gland is compartmentalized, with base and isthmus regions supported by two separate independent stem cell populations. Isthmus stem cells are rapidly cycling, with a broad expression signature, and undergo “punctuated” neutral drift dynamics.