Epithelial expression of Gata4 and Sox2 regulates specification of the squamous-columnar junction via MAPK/ERK signaling in mice.

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Tytuł:: Epithelial expression of Gata4 and Sox2 regulates specification of the squamous-columnar junction via MAPK/ERK signaling in mice.
Autorzy:: Sankoda N; Department of Life Science Frontiers, Center for iPS Cell Research and Application (CiRA), Kyoto University, Kyoto, 606-8507, Japan.; Department of Surgery, Kyoto University Graduate School of Medicine, Kyoto, 606-8507, Japan.; Division of Stem Cell Pathology, Center for Experimental Medicine and Systems Biology, Institute of Medical Science, University of Tokyo, Tokyo, 108-8639, Japan.
Tanabe W; Department of Life Science Frontiers, Center for iPS Cell Research and Application (CiRA), Kyoto University, Kyoto, 606-8507, Japan.; Department of Gastroenterology, Kyoto University Graduate School of Medicine, Kyoto, 606-8507, Japan.
Tanaka A; Department of Life Science Frontiers, Center for iPS Cell Research and Application (CiRA), Kyoto University, Kyoto, 606-8507, Japan.
Shibata H; Department of Otolaryngology, Gifu University Graduate School of Medicine, Gifu, 501-1194, Japan.
Woltjen K; Department of Life Science Frontiers, Center for iPS Cell Research and Application (CiRA), Kyoto University, Kyoto, 606-8507, Japan.; Hakubi Center for Advanced Research, Kyoto University, Kyoto, 606-8501, Japan.
Chiba T; Department of Gastroenterology, Kyoto University Graduate School of Medicine, Kyoto, 606-8507, Japan.
Haga H; Department of Diagnostic Pathology, Kyoto University Hospital, Kyoto, 606-8507, Japan.
Sakai Y; Department of Surgery, Kyoto University Graduate School of Medicine, Kyoto, 606-8507, Japan.
Mandai M; Department of Gynecology and Obstetrics, Kyoto University Hospital, Kyoto, 606-8507, Japan.
Yamamoto T; Department of Life Science Frontiers, Center for iPS Cell Research and Application (CiRA), Kyoto University, Kyoto, 606-8507, Japan.; AMED-CREST, AMED 1-7-1 Otemachi, Chiyodaku, Tokyo, 100-0004, Japan.; Institute for the Advanced Study of Human Biology (WPI-ASHBi), Kyoto University, Yoshida-Konoe-cho, Sakyo-ku, Kyoto, 606-8501, Japan.; Medical-risk Avoidance Based on iPS Cells Team, RIKEN Center for Advanced Intelligence Project (AIP), Kyoto, 606-8507, Japan.
Yamada Y; Division of Stem Cell Pathology, Center for Experimental Medicine and Systems Biology, Institute of Medical Science, University of Tokyo, Tokyo, 108-8639, Japan.; AMED-CREST, AMED 1-7-1 Otemachi, Chiyodaku, Tokyo, 100-0004, Japan.
Uemoto S; Department of Surgery, Kyoto University Graduate School of Medicine, Kyoto, 606-8507, Japan.
Kawaguchi Y; Department of Life Science Frontiers, Center for iPS Cell Research and Application (CiRA), Kyoto University, Kyoto, 606-8507, Japan. .
Źródło:: Nature communications [Nat Commun] 2021 Jan 25; Vol. 12 (1), pp. 560. Date of Electronic Publication: 2021 Jan 25.
Typ publikacji:: Journal Article; Research Support, Non-U.S. Gov't
Język:: English
Imprint Name(s):: Original Publication: [London] : Nature Pub. Group
MeSH Terms:: Gene Expression Regulation*
Epithelial Cells/*metabolism
GATA4 Transcription Factor/*genetics
Intercellular Junctions/*genetics
MAP Kinase Signaling System/*genetics
SOXB1 Transcription Factors/*genetics
Animals ; Cells, Cultured ; Female ; GATA4 Transcription Factor/metabolism ; Gastric Mucosa/metabolism ; Keratin-7/genetics ; Keratin-7/metabolism ; Mice, 129 Strain ; Mice, Inbred C57BL ; Mice, Inbred ICR ; Mice, Knockout ; Mice, Transgenic ; SOXB1 Transcription Factors/metabolism ; Mice
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Substance Nomenclature:: 0 (GATA4 Transcription Factor)
0 (Keratin-7)
0 (Krt7 protein, mouse)
0 (SOXB1 Transcription Factors)
Entry Date(s):: Date Created: 20210126 Date Completed: 20210208 Latest Revision: 20240226
Update Code:: 20240226
PubMed Central ID:: PMC7835245
DOI:: 10.1038/s41467-021-20906-0
PMID:: 33495473
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The squamous-columnar junction (SCJ) is a boundary consisting of precisely positioned transitional epithelium between the squamous and columnar epithelium. Transitional epithelium is a hotspot for precancerous lesions, and is therefore clinically important; however, the origins and physiological properties of transitional epithelium have not been fully elucidated. Here, by using mouse genetics, lineage tracing, and organoid culture, we examine the development of the SCJ in the mouse stomach, and thus define the unique features of transitional epithelium. We find that two transcription factors, encoded by Sox2 and Gata4, specify primitive transitional epithelium into squamous and columnar epithelium. The proximal-distal segregation of Sox2 and Gata4 expression establishes the boundary of the unspecified transitional epithelium between committed squamous and columnar epithelium. Mechanistically, Gata4-mediated expression of the morphogen Fgf10 in the distal stomach and Sox2-mediated Fgfr2 expression in the proximal stomach induce the intermediate regional activation of MAPK/ERK, which prevents the differentiation of transitional epithelial cells within the SCJ boundary. Our results have implications for tissue regeneration and tumorigenesis, which are related to the SCJ.

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