Prominin-1 promotes restitution of the murineMAQ:Editorial Office/AASLD: Please indicate if a visual abstract will be forthcoming for this article. extrahepatic biliary luminal epithelium following cholestatic liver injury
Background and Aims:. Restitution of the extrahepatic biliary luminal epithelium in cholangiopathies is poorly understood. Prominin-1 (Prom1) is a key component of epithelial ciliary body of stem/progenitor cells. Given that intrahepatic Prom1-expressing progenitor cells undergo cholangiocyte differ...
| Main Authors: | , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Wolters Kluwer Health/LWW
2023-02-01
|
| Series: | Hepatology Communications |
| Online Access: | http://journals.lww.com/10.1097/HC9.0000000000000018 |
| _version_ | 1811161633947385856 |
|---|---|
| author | Allen Zhong Celia Short Jiabo Xu G. Esteban Fernandez Nicolas Malkoff Nicolas Noriega Theresa Yeo Larry Wang Nirmala Mavila Kinji Asahina Kasper S. Wang |
| author_facet | Allen Zhong Celia Short Jiabo Xu G. Esteban Fernandez Nicolas Malkoff Nicolas Noriega Theresa Yeo Larry Wang Nirmala Mavila Kinji Asahina Kasper S. Wang |
| author_sort | Allen Zhong |
| collection | DOAJ |
| description | Background and Aims:. Restitution of the extrahepatic biliary luminal epithelium in cholangiopathies is poorly understood. Prominin-1 (Prom1) is a key component of epithelial ciliary body of stem/progenitor cells. Given that intrahepatic Prom1-expressing progenitor cells undergo cholangiocyte differentiation, we hypothesized that Prom1 may promote restitution of the extrahepatic bile duct (EHBD) epithelium following injury.
Approach and Results:. Utilizing various murine biliary injury models, we identified Prom1-expressing cells in the peribiliary glands of the EHBD. These Prom1-expressing cells are progenitor cells which give rise to cholangiocytes as part of the normal maintenance of the EHBD epithelium. Following injury, these cells proliferate significantly more rapidly to re-populate the biliary luminal epithelium. Null mutation of Prom1 leads to significantly >10-fold dilated peribiliary glands following rhesus rotavirus–mediated biliary injury. Cultured organoids derived from Prom1 knockout mice are comprised of biliary progenitor cells with altered apical-basal cellular polarity, significantly fewer and shorter cilia, and decreased organoid proliferation dynamics consistent with impaired cell motility.
Conclusions:. We, therefore, conclude that Prom1 is involved in biliary epithelial restitution following biliary injury in part through its role in supporting cell polarity. |
| first_indexed | 2024-04-10T06:17:30Z |
| format | Article |
| id | doaj.art-909ab46dd7434b64b57f08a48c3dd368 |
| institution | Directory Open Access Journal |
| issn | 2471-254X |
| language | English |
| last_indexed | 2024-04-10T06:17:30Z |
| publishDate | 2023-02-01 |
| publisher | Wolters Kluwer Health/LWW |
| record_format | Article |
| series | Hepatology Communications |
| spelling | doaj.art-909ab46dd7434b64b57f08a48c3dd3682023-03-02T06:30:44ZengWolters Kluwer Health/LWWHepatology Communications2471-254X2023-02-0172e0018e001810.1097/HC9.0000000000000018HC90000000000000018Prominin-1 promotes restitution of the murineMAQ:Editorial Office/AASLD: Please indicate if a visual abstract will be forthcoming for this article. extrahepatic biliary luminal epithelium following cholestatic liver injuryAllen Zhong0Celia Short1Jiabo Xu2G. Esteban Fernandez3Nicolas Malkoff4Nicolas Noriega5Theresa Yeo6Larry Wang7Nirmala Mavila8Kinji Asahina9Kasper S. Wang10 1 Developmental Biology, Regenerative Medicine, and Stem Cell Program, The Saban Research Institute, Children’s Hospital of Los Angeles, Los Angeles, California, USA 1 Developmental Biology, Regenerative Medicine, and Stem Cell Program, The Saban Research Institute, Children’s Hospital of Los Angeles, Los Angeles, California, USA 1 Developmental Biology, Regenerative Medicine, and Stem Cell Program, The Saban Research Institute, Children’s Hospital of Los Angeles, Los Angeles, California, USA 2 Cellular Imaging Core, The Saban Research Institute, Children’s Hospital of Los Angeles, Los Angeles, California, USA 1 Developmental Biology, Regenerative Medicine, and Stem Cell Program, The Saban Research Institute, Children’s Hospital of Los Angeles, Los Angeles, California, USA 1 Developmental Biology, Regenerative Medicine, and Stem Cell Program, The Saban Research Institute, Children’s Hospital of Los Angeles, Los Angeles, California, USA 1 Developmental Biology, Regenerative Medicine, and Stem Cell Program, The Saban Research Institute, Children’s Hospital of Los Angeles, Los Angeles, California, USA 3 Department of Pathology, Children’s Hospital Los Angeles, Los Angeles, California, USA 4 Department of Medicine, Cedars Sinai Medical Center, Los Angeles, California, USA 5 Central Research Laboratory, Shiga University of Medical Science, Ōtsu, Shiga Prefecture, Japan 1 Developmental Biology, Regenerative Medicine, and Stem Cell Program, The Saban Research Institute, Children’s Hospital of Los Angeles, Los Angeles, California, USABackground and Aims:. Restitution of the extrahepatic biliary luminal epithelium in cholangiopathies is poorly understood. Prominin-1 (Prom1) is a key component of epithelial ciliary body of stem/progenitor cells. Given that intrahepatic Prom1-expressing progenitor cells undergo cholangiocyte differentiation, we hypothesized that Prom1 may promote restitution of the extrahepatic bile duct (EHBD) epithelium following injury. Approach and Results:. Utilizing various murine biliary injury models, we identified Prom1-expressing cells in the peribiliary glands of the EHBD. These Prom1-expressing cells are progenitor cells which give rise to cholangiocytes as part of the normal maintenance of the EHBD epithelium. Following injury, these cells proliferate significantly more rapidly to re-populate the biliary luminal epithelium. Null mutation of Prom1 leads to significantly >10-fold dilated peribiliary glands following rhesus rotavirus–mediated biliary injury. Cultured organoids derived from Prom1 knockout mice are comprised of biliary progenitor cells with altered apical-basal cellular polarity, significantly fewer and shorter cilia, and decreased organoid proliferation dynamics consistent with impaired cell motility. Conclusions:. We, therefore, conclude that Prom1 is involved in biliary epithelial restitution following biliary injury in part through its role in supporting cell polarity.http://journals.lww.com/10.1097/HC9.0000000000000018 |
| spellingShingle | Allen Zhong Celia Short Jiabo Xu G. Esteban Fernandez Nicolas Malkoff Nicolas Noriega Theresa Yeo Larry Wang Nirmala Mavila Kinji Asahina Kasper S. Wang Prominin-1 promotes restitution of the murineMAQ:Editorial Office/AASLD: Please indicate if a visual abstract will be forthcoming for this article. extrahepatic biliary luminal epithelium following cholestatic liver injury Hepatology Communications |
| title | Prominin-1 promotes restitution of the murineMAQ:Editorial Office/AASLD: Please indicate if a visual abstract will be forthcoming for this article. extrahepatic biliary luminal epithelium following cholestatic liver injury |
| title_full | Prominin-1 promotes restitution of the murineMAQ:Editorial Office/AASLD: Please indicate if a visual abstract will be forthcoming for this article. extrahepatic biliary luminal epithelium following cholestatic liver injury |
| title_fullStr | Prominin-1 promotes restitution of the murineMAQ:Editorial Office/AASLD: Please indicate if a visual abstract will be forthcoming for this article. extrahepatic biliary luminal epithelium following cholestatic liver injury |
| title_full_unstemmed | Prominin-1 promotes restitution of the murineMAQ:Editorial Office/AASLD: Please indicate if a visual abstract will be forthcoming for this article. extrahepatic biliary luminal epithelium following cholestatic liver injury |
| title_short | Prominin-1 promotes restitution of the murineMAQ:Editorial Office/AASLD: Please indicate if a visual abstract will be forthcoming for this article. extrahepatic biliary luminal epithelium following cholestatic liver injury |
| title_sort | prominin 1 promotes restitution of the murinemaq editorial office aasld please indicate if a visual abstract will be forthcoming for this article extrahepatic biliary luminal epithelium following cholestatic liver injury |
| url | http://journals.lww.com/10.1097/HC9.0000000000000018 |
| work_keys_str_mv | AT allenzhong prominin1promotesrestitutionofthemurinemaqeditorialofficeaasldpleaseindicateifavisualabstractwillbeforthcomingforthisarticleextrahepaticbiliaryluminalepitheliumfollowingcholestaticliverinjury AT celiashort prominin1promotesrestitutionofthemurinemaqeditorialofficeaasldpleaseindicateifavisualabstractwillbeforthcomingforthisarticleextrahepaticbiliaryluminalepitheliumfollowingcholestaticliverinjury AT jiaboxu prominin1promotesrestitutionofthemurinemaqeditorialofficeaasldpleaseindicateifavisualabstractwillbeforthcomingforthisarticleextrahepaticbiliaryluminalepitheliumfollowingcholestaticliverinjury AT gestebanfernandez prominin1promotesrestitutionofthemurinemaqeditorialofficeaasldpleaseindicateifavisualabstractwillbeforthcomingforthisarticleextrahepaticbiliaryluminalepitheliumfollowingcholestaticliverinjury AT nicolasmalkoff prominin1promotesrestitutionofthemurinemaqeditorialofficeaasldpleaseindicateifavisualabstractwillbeforthcomingforthisarticleextrahepaticbiliaryluminalepitheliumfollowingcholestaticliverinjury AT nicolasnoriega prominin1promotesrestitutionofthemurinemaqeditorialofficeaasldpleaseindicateifavisualabstractwillbeforthcomingforthisarticleextrahepaticbiliaryluminalepitheliumfollowingcholestaticliverinjury AT theresayeo prominin1promotesrestitutionofthemurinemaqeditorialofficeaasldpleaseindicateifavisualabstractwillbeforthcomingforthisarticleextrahepaticbiliaryluminalepitheliumfollowingcholestaticliverinjury AT larrywang prominin1promotesrestitutionofthemurinemaqeditorialofficeaasldpleaseindicateifavisualabstractwillbeforthcomingforthisarticleextrahepaticbiliaryluminalepitheliumfollowingcholestaticliverinjury AT nirmalamavila prominin1promotesrestitutionofthemurinemaqeditorialofficeaasldpleaseindicateifavisualabstractwillbeforthcomingforthisarticleextrahepaticbiliaryluminalepitheliumfollowingcholestaticliverinjury AT kinjiasahina prominin1promotesrestitutionofthemurinemaqeditorialofficeaasldpleaseindicateifavisualabstractwillbeforthcomingforthisarticleextrahepaticbiliaryluminalepitheliumfollowingcholestaticliverinjury AT kasperswang prominin1promotesrestitutionofthemurinemaqeditorialofficeaasldpleaseindicateifavisualabstractwillbeforthcomingforthisarticleextrahepaticbiliaryluminalepitheliumfollowingcholestaticliverinjury |