研究动态
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猪和人类胆管树中的一种出生后的肝/胰干/祖细胞网络。

A postnatal network of co-hepato/pancreatic stem/progenitors in the biliary trees of pigs and humans.

发表日期:2023 Aug 01
作者: Wencheng Zhang, Xicheng Wang, Giacomo Lanzoni, Eliane Wauthier, Sean Simpson, Jennifer Ashley Ezzell, Amanda Allen, Carolyn Suitt, Jonah Krolik, Alexander Jhirad, Juan Dominguez-Bendala, Vincenzo Cardinale, Domenico Alvaro, Diletta Overi, Eugenio Gaudio, Praveen Sethupathy, Guido Carpino, Christopher Adin, Jorge A Piedrahita, Kyle Mathews, Zhiying He, Lola McAdams Reid
来源: npj Regenerative Medicine

摘要:

猪和人的Brunner's腺位于十二指肠粘膜下层、肝内外胆管树的胆囊旁腺(PBGs)以及胰内胆管树中的胰管腺(PDGs)中存在一个共同的肝/胰干/祖细胞网络,共同支持出生后的肝脏和胰腺再生。这个网络在人类出生后一生都可以找到,在猪出生后至少持续到青春期。在猪的体内,这些干/祖细胞数量最多的是在Brunner's腺和靠近十二指肠的PDGs中,在人类体内则是在Brunner's腺和肝/胰共同管道中的PBGs中。在猪的PDGs中和人类所有的PDGs中,只有承诺分化的单能或双能祖细胞。肝/胰相关的RNA-seq数据表明,这些干/祖细胞具有遗传特征,基于相关性、分级聚类、差异基因表达和主成分分析(PCA)。基因表达包括多能性基因(SOX2, OCT4)、内胚叶转录因子(e.g. SOX9, SOX17, PDX1)、其他干细胞特征(e.g. NCAM, CD44, 碘化物钠离子转运体或NIS)以及增殖生物标志物(Ki67)的代表性特征。肝/胰多能性通过干/祖细胞在不同离体条件下或移植为器官样片块时的反应进行了证明,可以分别接种于肝脏和胰腺中。因此,猪是使用这些干/祖细胞进行肝脏和胰腺功能障碍的转化/临床研究的合理宿主。© 2023. 作者。
A network of co-hepato/pancreatic stem/progenitors exists in pigs and humans in Brunner's Glands in the submucosa of the duodenum, in peribiliary glands (PBGs) of intrahepatic and extrahepatic biliary trees, and in pancreatic duct glands (PDGs) of intrapancreatic biliary trees, collectively supporting hepatic and pancreatic regeneration postnatally. The network is found in humans postnatally throughout life and, so far, has been demonstrated in pigs postnatally at least through to young adulthood. These stem/progenitors in vivo in pigs are in highest numbers in Brunner's Glands and in PDGs nearest the duodenum, and in humans are in Brunner's Glands and in PBGs in the hepato/pancreatic common duct, a duct missing postnatally in pigs. Elsewhere in PDGs in pigs and in all PDGs in humans are only committed unipotent or bipotent progenitors. Stem/progenitors have genetic signatures in liver/pancreas-related RNA-seq data based on correlation, hierarchical clustering, differential gene expression and principal component analyses (PCA). Gene expression includes representative traits of pluripotency genes (SOX2, OCT4), endodermal transcription factors (e.g. SOX9, SOX17, PDX1), other stem cell traits (e.g. NCAM, CD44, sodium iodide symporter or NIS), and proliferation biomarkers (Ki67). Hepato/pancreatic multipotentiality was demonstrated by the stem/progenitors' responses under distinct ex vivo conditions or in vivo when patch grafted as organoids onto the liver versus the pancreas. Therefore, pigs are logical hosts for translational/preclinical studies for cell therapies with these stem/progenitors for hepatic and pancreatic dysfunctions.© 2023. The Author(s).