TY - JOUR
T1 - Defining the Identity and Dynamics of Adult Gastric Isthmus Stem Cells
AU - Han, Seungmin
AU - Fink, Juergen
AU - Jörg, David J.
AU - Lee, Eunmin
AU - Yum, Min Kyu
AU - Chatzeli, Lemonia
AU - Merker, Sebastian R.
AU - Josserand, Manon
AU - Trendafilova, Teodora
AU - Andersson-Rolf, Amanda
AU - Dabrowska, Catherine
AU - Kim, Hyunki
AU - Naumann, Ronald
AU - Lee, Ji Hyun
AU - Sasaki, Nobuo
AU - Mort, Richard Lester
AU - Basak, Onur
AU - Clevers, Hans
AU - Stange, Daniel E.
AU - Philpott, Anna
AU - Kim, Jong Kyoung
AU - Simons, Benjamin D.
AU - Koo, Bon Kyoung
N1 - Publisher Copyright:
© 2019 The Authors
PY - 2019/9/5
Y1 - 2019/9/5
N2 - 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.
AB - 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.
KW - biophysical modeling
KW - deep tissue imaging
KW - gastric corpus isthmus stem cell
KW - intestine
KW - Lgr5
KW - punctuated neutral drift
KW - single-cell RNA-seq
KW - Troy
KW - two stem cell compartments
KW - unbiased genetic labeling
UR - http://www.scopus.com/inward/record.url?scp=85071504710&partnerID=8YFLogxK
U2 - 10.1016/j.stem.2019.07.008
DO - 10.1016/j.stem.2019.07.008
M3 - Article
C2 - 31422913
AN - SCOPUS:85071504710
SN - 1934-5909
VL - 25
SP - 342-356.e7
JO - Cell Stem Cell
JF - Cell Stem Cell
IS - 3
ER -