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

Kenichiro Furuyama; Yoshiya Kawaguchi; Haruhiko Akiyama; Masashi Horiguchi; Sota Kodama; Takeshi Kuhara; Shinichi Hosokawa; Ashraf Elbahrawy; Tsunemitsu Soeda; Masayuki Koizumi; Toshihiko Masui; Michiya Kawaguchi; Kyoichi Takaori; Ryuichiro Doi; Eiichiro Nishi; Ryosuke Kakinoki; Jian Min Deng; Richard R. Behringer; Takashi Nakamura; Shinji Uemoto

doi:10.1038/ng.722

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

Kenichiro Furuyama, Yoshiya Kawaguchi, Haruhiko Akiyama, Masashi Horiguchi, Sota Kodama, Takeshi Kuhara, Shinichi Hosokawa, Ashraf Elbahrawy, Tsunemitsu Soeda, Masayuki Koizumi, Toshihiko Masui, Michiya Kawaguchi, Kyoichi Takaori, Ryuichiro Doi, Eiichiro Nishi, Ryosuke Kakinoki, Jian Min Deng, Richard R. Behringer, Takashi Nakamura, Shinji Uemoto

Genetics

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686 Scopus citations

Abstract

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.

Original language	English (US)
Pages (from-to)	34-41
Number of pages	8
Journal	Nature Genetics
Volume	43
Issue number	1
DOIs	https://doi.org/10.1038/ng.722
State	Published - Jan 2011

ASJC Scopus subject areas

Genetics

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Furuyama, K., Kawaguchi, Y., Akiyama, H., Horiguchi, M., Kodama, S., Kuhara, T., Hosokawa, S., Elbahrawy, A., Soeda, T., Koizumi, M., Masui, T., Kawaguchi, M., Takaori, K., Doi, R., Nishi, E., Kakinoki, R., Deng, J. M., Behringer, R. R., Nakamura, T., & Uemoto, S. (2011). Continuous cell supply from a Sox9-expressing progenitor zone in adult liver, exocrine pancreas and intestine. Nature Genetics, 43(1), 34-41. https://doi.org/10.1038/ng.722

Furuyama, K, Kawaguchi, Y, Akiyama, H, Horiguchi, M, Kodama, S, Kuhara, T, Hosokawa, S, Elbahrawy, A, Soeda, T, Koizumi, M, Masui, T, Kawaguchi, M, Takaori, K, Doi, R, Nishi, E, Kakinoki, R, Deng, JM, Behringer, RR, Nakamura, T & Uemoto, S 2011, 'Continuous cell supply from a Sox9-expressing progenitor zone in adult liver, exocrine pancreas and intestine', Nature Genetics, vol. 43, no. 1, pp. 34-41. https://doi.org/10.1038/ng.722

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

abstract = "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.",

author = "Kenichiro Furuyama and Yoshiya Kawaguchi and Haruhiko Akiyama and Masashi Horiguchi and Sota Kodama and Takeshi Kuhara and Shinichi Hosokawa and Ashraf Elbahrawy and Tsunemitsu Soeda and Masayuki Koizumi and Toshihiko Masui and Michiya Kawaguchi and Kyoichi Takaori and Ryuichiro Doi and Eiichiro Nishi and Ryosuke Kakinoki and Deng, {Jian Min} and Behringer, {Richard R.} and Takashi Nakamura and Shinji Uemoto",

note = "Funding Information: We thank A. Fukuda and M. Gannon for critical discussions and reading of the manuscript, Y. Ishiura and K. Fukazawa for technical help, C.V.E. Wright for Pdx1 antibody, P. Soriano for Rosa26R mice and the staff of the Institute of Laboratory Animals of Kyoto University for animal care. This work was supported by research grants from the Ministry of Education, Culture, Sports, Science and Technology of Japan and the US National Institutes of Health.",

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AU - Kawaguchi, Yoshiya

AU - Akiyama, Haruhiko

AU - Horiguchi, Masashi

AU - Kodama, Sota

AU - Kuhara, Takeshi

AU - Hosokawa, Shinichi

AU - Elbahrawy, Ashraf

AU - Soeda, Tsunemitsu

AU - Koizumi, Masayuki

AU - Masui, Toshihiko

AU - Kawaguchi, Michiya

AU - Takaori, Kyoichi

AU - Doi, Ryuichiro

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AU - Kakinoki, Ryosuke

AU - Deng, Jian Min

AU - Behringer, Richard R.

AU - Nakamura, Takashi

AU - Uemoto, Shinji

N1 - Funding Information: We thank A. Fukuda and M. Gannon for critical discussions and reading of the manuscript, Y. Ishiura and K. Fukazawa for technical help, C.V.E. Wright for Pdx1 antibody, P. Soriano for Rosa26R mice and the staff of the Institute of Laboratory Animals of Kyoto University for animal care. This work was supported by research grants from the Ministry of Education, Culture, Sports, Science and Technology of Japan and the US National Institutes of Health.

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N2 - 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.

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

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