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Defining the Identity and Dynamics of Adult Gastric Isthmus Stem Cells

50 Pages Posted: 16 Jul 2018 Sneak Peek Status: Published

See all articles by Juergen Fink

Juergen Fink

University of Cambridge - Stem Cell Institute

Seungmin Han

University of Cambridge - Stem Cell Institute

David J. Jörg

University of Cambridge - Cavendish Laboratory

Sebastian R. Merker

Dresden University of Technology - Department of Visceral, Thoracic and Vascular Surgery

Eunmin Lee

Daegu Gyeongbuk Institute of Science and Technology (DGIST) - Department of New Biology

Min Kyu Yum

University of Cambridge - Stem Cell Institute

Ji-Hyun Lee

Institute of Molecular Biotechnology

Manon Josserand

University of Cambridge - Stem Cell Institute

Teodora Trendafilova

University of Cambridge - Stem Cell Institute

Amanda Andersson-Rolf

University of Cambridge - Stem Cell Institute

Catherine Dabrowska

University of Cambridge - Stem Cell Institute

Hyunki Kim

University of Cambridge - Stem Cell Institute

Nobuo Sasaki

Keio University - Division of Gastroenterology and Hepatology

Richard Lester Mort

Lancaster University - Division of Biomedical and Life Sciences

Onur Basak

Utrecht University - University Medical Center (Utrecht)

Hans Clevers

Utrecht University - University Medical Center (Utrecht); Princess Máxima Center for Pediatric Oncology

Daniel E. Stange

University of Cambridge - Stem Cell Institute

Jong-Kyoung Kim

Korea Conformity Laboratories

Benjamin D. Simons

University of Cambridge - Stem Cell Institute

Bonkyoung Koo

University of Cambridge - Stem Cell Institute

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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.

Suggested Citation

Fink, Juergen and Han, Seungmin and Jörg, David J. and Merker, Sebastian R. and Lee, Eunmin and Yum, Min Kyu and Lee, Ji-Hyun and Josserand, Manon and Trendafilova, Teodora and Andersson-Rolf, Amanda and Dabrowska, Catherine and Kim, Hyunki and Sasaki, Nobuo and Mort, Richard Lester and Basak, Onur and Clevers, Hans and Stange, Daniel E. and Kim, Jong-Kyoung and Simons, Benjamin D. and Koo, Bonkyoung, Defining the Identity and Dynamics of Adult Gastric Isthmus Stem Cells (2018). Available at SSRN: https://ssrn.com/abstract=3213913 or http://dx.doi.org/10.2139/ssrn.3213913
This is a paper under consideration at Cell Press and has not been peer-reviewed.

Juergen Fink

University of Cambridge - Stem Cell Institute

United Kingdom

Seungmin Han

University of Cambridge - Stem Cell Institute

United Kingdom

David J. Jörg

University of Cambridge - Cavendish Laboratory

United Kingdom

Sebastian R. Merker

Dresden University of Technology - Department of Visceral, Thoracic and Vascular Surgery

Germany

Eunmin Lee

Daegu Gyeongbuk Institute of Science and Technology (DGIST) - Department of New Biology

Korea, Republic of (South Korea)

Min Kyu Yum

University of Cambridge - Stem Cell Institute

United Kingdom

Ji-Hyun Lee

Institute of Molecular Biotechnology

Austria

Manon Josserand

University of Cambridge - Stem Cell Institute

United Kingdom

Teodora Trendafilova

University of Cambridge - Stem Cell Institute

United Kingdom

Amanda Andersson-Rolf

University of Cambridge - Stem Cell Institute

United Kingdom

Catherine Dabrowska

University of Cambridge - Stem Cell Institute

United Kingdom

Hyunki Kim

University of Cambridge - Stem Cell Institute

United Kingdom

Nobuo Sasaki

Keio University - Division of Gastroenterology and Hepatology

Japan

Richard Lester Mort

Lancaster University - Division of Biomedical and Life Sciences

Lancaster
United Kingdom

Onur Basak

Utrecht University - University Medical Center (Utrecht)

Utrecht, 3584 CX
Netherlands

Hans Clevers

Utrecht University - University Medical Center (Utrecht)

Utrecht, 3584 CX
Netherlands

Princess Máxima Center for Pediatric Oncology

Heidelberglaan 25
3584 CS Utrecht
Germany

Daniel E. Stange

University of Cambridge - Stem Cell Institute

United Kingdom

Jong-Kyoung Kim

Korea Conformity Laboratories ( email )

Seoul
Korea, Republic of (South Korea)

Benjamin D. Simons

University of Cambridge - Stem Cell Institute ( email )

United Kingdom

Bonkyoung Koo (Contact Author)

University of Cambridge - Stem Cell Institute ( email )

United Kingdom

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