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