Essential role of Notch/Hes1 signaling in postnatal pancreatic exocrine development
Essential role of Notch/Hes1 signaling in postnatal pancreatic exocrine development
复制标题
Notch/Hes1信号在出生后胰腺外分泌发育中的重要作用
DOI：
10.1007/s00535-021-01779-y
复制
发表时间：
2021
影响因子：
6.3
通讯作者：
Seno H.
中科院分区：
文献类型：
--
作者：
Kuriyama K;Kodama Y;Shiokawa M;Nishikawa Y;Marui S;Kuwada T;Sogabe Y;Kakiuchi N;Tomono T;Matsumori T;Mima A;Morita T;Ueda T;Tsuda M;Yamauchi Y;Sakuma Y;Ota Y;Maruno T;Uza N;Kageyama R;Chiba T;Seno H.
背景Notch/Hes 1信号通路在胰腺祖细胞的命运中起重要作用。然而，其功能在出生后胰腺成熟尚未完全阐明.MethodsWe产生conditional Hes 1敲除和/或Notch胞内结构域（NICD）过表达小鼠在Ptf 1a-或Pdx 1-阳性胰腺祖细胞和分析胰腺tissues. ResultsBoth Ptf 1acre/+; Hes 1f/fandPtf 1acre/+; Rosa 26 NICD小鼠在P0.然而，Ptf 1acre/+; Hes 1f/f小鼠胰腺尾部外分泌组织萎缩，4周龄时被脂肪组织取代，凋亡细胞增加，中央腺泡细胞减少。在Ptf 1acre/+; Hes 1f/f; Rosa 26 NICD小鼠中，NICD过表达完全挽救了这种受损的外分泌发育，表明通过Hes 1以外的Notch信号通路进行补偿。相反，Pdx 1-Cre; Hes 1f/f小鼠表现出受损的出生后外分泌发育的胰腺头部和尾部，揭示胚胎Hes 1表达的时间和分布影响出生后外分泌组织development.ConclusionsNotch信号转导有一个重要的作用，胰腺祖细胞的出生后成熟的外分泌组织，部分通过中央腺泡细胞的形成。
BackgroundNotch/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.MethodsWe generated conditionalHes1knockout and/or Notch intracellular domain (NICD) overexpression mice in Ptf1a- or Pdx1-positive pancreatic progenitor cells and analyzed pancreatic tissues.ResultsBothPtf1acre/+; Hes1f/fandPtf1acre/+; Rosa26NICDmice showed normal pancreatic development at P0. However, exocrine tissue of the pancreatic tail inPtf1acre/+; Hes1f/fmice 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 inPtf1acre/+; Hes1f/f; Rosa26NICDmice, suggesting compensation by a Notch signaling pathway other than Hes1. Conversely,Pdx1-Cre; Hes1f/fmice 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.ConclusionsNotch signaling has an essential role in pancreatic progenitor cells for the postnatal maturation of exocrine tissue, partly through the formation of centroacinar cells.