Continuous cell supply from a Sox9-expressing progenitor zone in adult liver, exocrine pancreas and intestine.
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.
Department of Surgery, Kyoto University Graduate School of Medicine, Kyoto, Japan.
Kenichiro
K
Furuyama
Yoshiya
Y
Kawaguchi
Haruhiko
H
Akiyama
Masashi
M
Horiguchi
Sota
S
Kodama
Takeshi
T
Kuhara
Shinichi
S
Hosokawa
Ashraf
A
Elbahrawy
Tsunemitsu
T
Soeda
Masayuki
M
Koizumi
Toshihiko
T
Masui
Michiya
M
Kawaguchi
Kyoichi
K
Takaori
Ryuichiro
R
Doi
Eiichiro
E
Nishi
Ryosuke
R
Kakinoki
Jian Min
JM
Deng
Richard R
RR
Behringer
Takashi
T
Nakamura
Shinji
S
Uemoto
D000818:Animals; D002454:Cell Differentiation; D004847:Epithelial Cells / Q000166:cytology / Q000378:metabolism; D007413:Intestinal Mucosa / Q000378:metabolism*; D007422:Intestines / Q000166:cytology; D008099:Liver / Q000166:cytology / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D010179:Pancreas / Q000166:cytology / Q000378:metabolism*; D055758:SOX9 Transcription Factor / Q000235:genetics / Q000378:metabolism*; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism*
D055758:SOX9 Transcription Factor; C527933:Sox9 protein, mouse