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Developing Biliary Atresia-like Model by Treating Human Liver Organoids with Polyinosinic:Polycytidylic Acid (Poly (I:C))

Background: We explored the feasibility of creating BA-like organoids by treating human liver organoids with Polyinosinic:Polycytidylic acid (Poly I:C). Methods: Organoids were developed from the liver parenchyma collected during Kasai portoenterostomy (BA) and surgery for other liver disorders (non...

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Autores principales: Chung, Patrick Ho-Yu, Babu, Rosana Ottakandathil, Wu, Zhongluan, Wong, Kenneth Kak-Yuen, Tam, Paul Kwong-Hang, Lui, Vincent Chi-Hang
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8928947/
https://www.ncbi.nlm.nih.gov/pubmed/35723330
http://dx.doi.org/10.3390/cimb44020045
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author Chung, Patrick Ho-Yu
Babu, Rosana Ottakandathil
Wu, Zhongluan
Wong, Kenneth Kak-Yuen
Tam, Paul Kwong-Hang
Lui, Vincent Chi-Hang
author_facet Chung, Patrick Ho-Yu
Babu, Rosana Ottakandathil
Wu, Zhongluan
Wong, Kenneth Kak-Yuen
Tam, Paul Kwong-Hang
Lui, Vincent Chi-Hang
author_sort Chung, Patrick Ho-Yu
collection PubMed
description Background: We explored the feasibility of creating BA-like organoids by treating human liver organoids with Polyinosinic:Polycytidylic acid (Poly I:C). Methods: Organoids were developed from the liver parenchyma collected during Kasai portoenterostomy (BA) and surgery for other liver disorders (non-BA). The non-BA organoids were co-cultured with poly I:C (40 µg/mL). The organoid morphology from both samples was compared on day 17. RNA-sequencing was performed to examine the transcriptomic differences. Results: Non-BA liver organoids developed into well-expanded spherical organoids with a single-cell layer of epithelial cells and a single vacuole inside. After poly I:C treatment, the majority of these organoids developed into an aberrant morphology with a high index of similarity to BA organoids which are multi-vacuoled and/or unexpanded. RNA-sequencing analysis revealed that 19 inflammatory genes were commonly expressed in both groups. Conditional cluster analysis revealed several genes (SOCS6, SOCS6.1, ARAF, CAMK2G, GNA1C, ITGA2, PRKACA, PTEN) that are involved in immune-mediated signaling pathway had a distinct pattern of expression in the poly I:C treated organoids. This resembled the expression pattern in BA organoids (p < 0.05). Conclusions: Poly I:C treated human liver organoids exhibit morphology and genetic signature highly compatible to organoids developed from BA liver samples. They are potential research materials to study immune-mediated inflammation in BA.
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spelling pubmed-89289472022-06-04 Developing Biliary Atresia-like Model by Treating Human Liver Organoids with Polyinosinic:Polycytidylic Acid (Poly (I:C)) Chung, Patrick Ho-Yu Babu, Rosana Ottakandathil Wu, Zhongluan Wong, Kenneth Kak-Yuen Tam, Paul Kwong-Hang Lui, Vincent Chi-Hang Curr Issues Mol Biol Article Background: We explored the feasibility of creating BA-like organoids by treating human liver organoids with Polyinosinic:Polycytidylic acid (Poly I:C). Methods: Organoids were developed from the liver parenchyma collected during Kasai portoenterostomy (BA) and surgery for other liver disorders (non-BA). The non-BA organoids were co-cultured with poly I:C (40 µg/mL). The organoid morphology from both samples was compared on day 17. RNA-sequencing was performed to examine the transcriptomic differences. Results: Non-BA liver organoids developed into well-expanded spherical organoids with a single-cell layer of epithelial cells and a single vacuole inside. After poly I:C treatment, the majority of these organoids developed into an aberrant morphology with a high index of similarity to BA organoids which are multi-vacuoled and/or unexpanded. RNA-sequencing analysis revealed that 19 inflammatory genes were commonly expressed in both groups. Conditional cluster analysis revealed several genes (SOCS6, SOCS6.1, ARAF, CAMK2G, GNA1C, ITGA2, PRKACA, PTEN) that are involved in immune-mediated signaling pathway had a distinct pattern of expression in the poly I:C treated organoids. This resembled the expression pattern in BA organoids (p < 0.05). Conclusions: Poly I:C treated human liver organoids exhibit morphology and genetic signature highly compatible to organoids developed from BA liver samples. They are potential research materials to study immune-mediated inflammation in BA. MDPI 2022-01-27 /pmc/articles/PMC8928947/ /pubmed/35723330 http://dx.doi.org/10.3390/cimb44020045 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Chung, Patrick Ho-Yu
Babu, Rosana Ottakandathil
Wu, Zhongluan
Wong, Kenneth Kak-Yuen
Tam, Paul Kwong-Hang
Lui, Vincent Chi-Hang
Developing Biliary Atresia-like Model by Treating Human Liver Organoids with Polyinosinic:Polycytidylic Acid (Poly (I:C))
title Developing Biliary Atresia-like Model by Treating Human Liver Organoids with Polyinosinic:Polycytidylic Acid (Poly (I:C))
title_full Developing Biliary Atresia-like Model by Treating Human Liver Organoids with Polyinosinic:Polycytidylic Acid (Poly (I:C))
title_fullStr Developing Biliary Atresia-like Model by Treating Human Liver Organoids with Polyinosinic:Polycytidylic Acid (Poly (I:C))
title_full_unstemmed Developing Biliary Atresia-like Model by Treating Human Liver Organoids with Polyinosinic:Polycytidylic Acid (Poly (I:C))
title_short Developing Biliary Atresia-like Model by Treating Human Liver Organoids with Polyinosinic:Polycytidylic Acid (Poly (I:C))
title_sort developing biliary atresia-like model by treating human liver organoids with polyinosinic:polycytidylic acid (poly (i:c))
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8928947/
https://www.ncbi.nlm.nih.gov/pubmed/35723330
http://dx.doi.org/10.3390/cimb44020045
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