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Regional Differences in Human Biliary Tissues and Corresponding In Vitro –Derived Organoids
Author(s) -
Rimland Casey A.,
Tilson Samantha G.,
Morell Carola M.,
Tomaz Rute A.,
Lu WeiYu,
Adams Simone E.,
Georgakopoulos Nikitas,
OtaizoCarrasquero Francisco,
Myers Timothy G.,
Ferdinand John R.,
Gieseck Richard L.,
Sampaziotis Fotios,
Tysoe Olivia C.,
Ross Alexander,
Kraiczy Judith M.,
Wesley Brandon,
Muraro Daniele,
Zilbauer Matthias,
Oniscu Gabriel C.,
Hannan Nicholas R.F.,
Forbes Stuart J.,
SaebParsy Kourosh,
Wynn Thomas A.,
Vallier Ludovic
Publication year - 2021
Publication title -
hepatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.488
H-Index - 361
eISSN - 1527-3350
pISSN - 0270-9139
DOI - 10.1002/hep.31252
Subject(s) - organoid , in vitro , biology , computational biology , chemistry , microbiology and biotechnology , biochemistry
Background and Aims Organoids provide a powerful system to study epithelia in vitro . Recently, this approach was applied successfully to the biliary tree, a series of ductular tissues responsible for the drainage of bile and pancreatic secretions. More precisely, organoids have been derived from ductal tissue located outside (extrahepatic bile ducts; EHBDs) or inside the liver (intrahepatic bile ducts; IHBDs). These organoids share many characteristics, including expression of cholangiocyte markers such as keratin (KRT) 19. However, the relationship between these organoids and their tissues of origin, and to each other, is largely unknown. Approach and Results Organoids were derived from human gallbladder, common bile duct, pancreatic duct, and IHBDs using culture conditions promoting WNT signaling. The resulting IHBD and EHBD organoids expressed stem/progenitor markers leucine‐rich repeat–containing G‐protein‐coupled receptor 5/prominin 1 and ductal markers KRT19/KRT7. However, RNA sequencing revealed that organoids conserve only a limited number of regional‐specific markers corresponding to their location of origin. Of particular interest, down‐regulation of biliary markers and up‐regulation of cell‐cycle genes were observed in organoids. IHBD and EHBD organoids diverged in their response to WNT signaling, and only IHBDs were able to express a low level of hepatocyte markers under differentiation conditions. Conclusions Taken together, our results demonstrate that differences exist not only between extrahepatic biliary organoids and their tissue of origin, but also between IHBD and EHBD organoids. This information may help to understand the tissue specificity of cholangiopathies and also to identify targets for therapeutic development.