Continuous cell supply from a Sox9-expressing progenitor zone in adult liver, exocrine pancreas and intestine

• Published in: Nature genetics Vol. 43; no. 1; pp. 34 - 41
• Main Authors: Kawaguchi, Yoshiya, Akiyama, Haruhiko, Furuyama, Kenichiro, Horiguchi, Masashi, Kodama, Sota, Kuhara, Takeshi, Hosokawa, Shinichi, Elbahrawy, Ashraf, Soeda, Tsunemitsu, Koizumi, Masayuki, Masui, Toshihiko, Kawaguchi, Michiya, Takaori, Kyoichi, Doi, Ryuichiro, Nishi, Eiichiro, Kakinoki, Ryosuke, Deng, Jian Min, Behringer, Richard R, Nakamura, Takashi, Uemoto, Shinji
• Format: Journal Article
• Language: English
• Published: New York Nature Publishing Group US 01.01.2011; Nature Publishing Group
• Subjects: 631/136/532/2118; 631/136/532/489; 631/208/199; Agriculture; Animal Genetics and Genomics; Animals; Biological and medical sciences; Biomedical and Life Sciences; Biomedicine; Cancer Research; Cell Differentiation; Epithelial Cells - cytology; Epithelial Cells - metabolism; Fundamental and applied biological sciences. Psychology; Gene expression; Gene Function; Genetic aspects; Genetics of eukaryotes. Biological and molecular evolution; Homeostasis; Human Genetics; Intestines; Intestines - cytology; Intestines - metabolism; Laboratory animals; Liver - cytology; Liver - metabolism; Mice; Mice, Knockout; Pancreas; Pancreas - cytology; Pancreas - metabolism; Physiological aspects; Proteins; Rodents; SOX9 Transcription Factor - genetics; SOX9 Transcription Factor - metabolism; Stem cells; Stem Cells - cytology; Stem Cells - metabolism; United States; Japan; Human; Adult; Digestive system; Liver; Exocrine pancreas
• ISSN: 1061-4036; 1546-1718
• DOI: 10.1038/ng.722

Yoshiya Kawaguchi and colleagues show that a Sox9-positive progenitor pool located in the epithelia of the biliary and pancreatic ducts of adult mice serves as a continuous source of intestinal cells, hepatocytes and pancreatic acinar cells, identifying a shared pathway underlying the cellular renewal of these adult endodermal organs. The liver and exocrine pancreas share a common structure, with functioning units (hepatic plates and pancreatic acini) connected to the ductal tree. Here we show that Sox9 is expressed throughout the biliary and pancreatic ductal epithelia, which are connected to the intestinal stem-cell zone. Cre-based lineage tracing showed that adult intestinal cells, hepatocytes and pancreatic acinar cells are supplied physiologically from Sox9-expressing progenitors. Combination of lineage analysis and hepatic injury experiments showed involvement of Sox9-positive precursors in liver regeneration. Embryonic pancreatic Sox9-expressing cells differentiate into all types of mature cells, but their capacity for endocrine differentiation diminishes shortly after birth, when endocrine cells detach from the epithelial lining of the ducts and form the islets of Langerhans. We observed a developmental switch in the hepatic progenitor cell type from Sox9-negative to Sox9-positive progenitors as the biliary tree develops. These results suggest interdependence between the structure and homeostasis of endodermal organs, with Sox9 expression being linked to progenitor status.