Defining the Identity and Dynamics of Adult Gastric Isthmus Stem Cells.

Seungmin Han,Manon Josserand,Min Kyu Yum,Anna Philpott,Teodora Trendafilova,Amanda Andersson-Rolf,Hyunki Kim,Catherine Dabrowska,Daniel E Stange,Lemonia Chatzeli,Hans Clevers,Ronald Naumann,Eunmin Lee,David J Jörg,Nobuo Sasaki,Sebastian R Merker,Benjamin D Simons,Onur Basak,J Lynn Fink ,Jong Kim ,Ji–Hyun Lee ,Richard L Mort ,Bon‐Kyoung Koo

doi:10.1016/j.stem.2019.07.008

Abstract

SummaryThe 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.

Highlights

The gastric corpus epithelium consists of long, single-layered glands populated by diverse gastric cell types, including pit, neck, parietal, and chief cells (Bartfeld and Koo, 2017; Mills and Shivdasani, 2011; Willet and Mills, 2016; Kim and Shivdasani, 2016)
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 isthmus stem cells (IsthSCs) maintain the pit-isthmus-neck region

Summary

Introduction

The gastric corpus epithelium consists of long, single-layered glands populated by diverse gastric cell types, including pit, neck, parietal, and chief cells (Bartfeld and Koo, 2017; Mills and Shivdasani, 2011; Willet and Mills, 2016; Kim and Shivdasani, 2016). Pit cells are located close to the stomach lumen and adjacent to proliferating cells in the isthmus region. Mucus neck and chief cells are located below the isthmus, toward the gland base. Acid-secreting parietal cells are present throughout the gland, except for the pit region. In common with other gastrointestinal (GI) epithelia, the corpus epithelium is replenished rapidly and constantly. As with other components of the GI tract, the corpus epithelium hosts a stem cell population in the gland base, marked by canonical, Wnt-responsive, stem cell markers, such as Troy

Methods

Results

Discussion

Conclusion