Essential role of Notch/Hes1 signaling in postnatal pancreatic exocrine development

• Published in: Journal of gastroenterology Vol. 56; no. 7; pp. 673 - 687
• Main Authors: Kuriyama, Katsutoshi, Kodama, Yuzo, Shiokawa, Masahiro, Nishikawa, Yoshihiro, Marui, Saiko, Kuwada, Takeshi, Sogabe, Yuko, Kakiuchi, Nobuyuki, Tomono, Teruko, Matsumori, Tomoaki, Mima, Atsushi, Morita, Toshihiro, Ueda, Tatsuki, Tsuda, Motoyuki, Yamauchi, Yuki, Sakuma, Yojiro, Ota, Yuji, Maruno, Takahisa, Uza, Norimitsu, Kageyama, Ryoichiro, Chiba, Tsutomu, Seno, Hiroshi
• Format: Journal Article
• Language: English
• Published: Singapore Springer Singapore 01.07.2021; Springer; Springer Nature B.V
• Subjects: Abdominal Surgery; Adipose tissues; Analysis; Apoptosis; Biliary Tract; Colorectal Surgery; Embryogenesis; Gastroenterology; Hepatology; Laboratories; Ligands; Medicine; Medicine & Public Health; Original Article―Liver; Pancreas; Progenitor cells; Signal transduction; Stem cells; Surgical Oncology; University graduates; Hes1; Centroacinar cell; Pancreas; Notch signaling; Postnatal development
• ISSN: 0944-1174; 1435-5922
• DOI: 10.1007/s00535-021-01779-y

Background Notch/Hes1 signaling has been shown to play a role in determining the fate of pancreatic progenitor cells. However, its function in postnatal pancreatic maturation is not fully elucidated. Methods We generated conditional Hes1 knockout and/or Notch intracellular domain (NICD) overexpression mice in Ptf1a- or Pdx1-positive pancreatic progenitor cells and analyzed pancreatic tissues. Results Both Ptf1a cre/ + ; Hes1 f/f and Ptf1a cre/ + ; Rosa26 NICD mice showed normal pancreatic development at P0. However, exocrine tissue of the pancreatic tail in Ptf1a cre/ + ; Hes1 f/f mice atrophied and was replaced by fat tissue by 4 weeks of age, with increased apoptotic cells and fewer centroacinar cells. This impaired exocrine development was completely rescued by NICD overexpression in Ptf1a cre/ + ; Hes1 f/f ; Rosa26 NICD mice, suggesting compensation by a Notch signaling pathway other than Hes1. Conversely, Pdx1-Cre; Hes1 f/f mice showed impaired postnatal exocrine development in both the pancreatic head and tail, revealing that the timing and distribution of embryonic Hes1 expression affects postnatal exocrine tissue development. Conclusions Notch signaling has an essential role in pancreatic progenitor cells for the postnatal maturation of exocrine tissue, partly through the formation of centroacinar cells.