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Conference Paper: Polyinosinic: polycytidylic acid [Poly(I:C)] treated liver organoids as a research model for biliary atresia
Title | Polyinosinic: polycytidylic acid [Poly(I:C)] treated liver organoids as a research model for biliary atresia |
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Authors | |
Issue Date | 2021 |
Publisher | John Wiley & Sons, Inc. The Journal's web site is located at http://www.hepatology.org/ |
Citation | AASLD 2021: The Liver Meeting (Virtual), 12-15 November 2021. In Hepatology, v. 74 n. 1, p. 1173A How to Cite? |
Abstract | Background: Biliary atresia (BA) is congenital disorder characterized by immune-mediated inflammation of the biliary systems resulting in life-threatening cholangiopathy In recent years, organoid technology has opened a new avenue for research in hepatobiliary diseases. Yet, the rarity of BA has limited the availability of human samples In this study, we explore the feasibility of creating a BA-like organoid by treating organoids from normal liver with Polyinosinic:Polycytidylic acid [Poly (I:C)], a synthetic immunostimulant that is structurally similar to a double-stranded RNA in virus Methods: BA
organoids were developed from liver parenchyma collected during Kasai portoenterostomy Control organoids were developed from the non-tumor part of hepatoblastoma and they were co-cultured with Poly I:C (40 µg/ml). The organoid morphology was compared on day 17 In addition, RNAsequencing were performed to determine the transcriptomic difference between these samples Results: Control organoids without any treatment developed into well-expanded spherical organoids with a single-cell layer of epithelial cells and a single vacuole inside In contrast, after Poly I:C treatment, majority of
these organoids developed into an aberrant morphology with a high index of similarity to BA organoids which were multivacuole and/or unexpanded (Figure 1A) RNA-sequencing analysis revealed that 19 inflammatory genes were commonly expressed in both groups They were selected for conditional
cluster analysis and several genes that are involved in immune-mediated signaling pathway (SOCS6, SOCS6 1, ARAF, CAMK2G, GNA1C, ITGA2, PRKACA, PTEN ) we found to have a distinct pattern of expression in the Poly I:C treated control organoids, resembling the expression profile in BA multi-vacuole and unexpanded organoids (p<0.05) (Figure 1B). Conclusion: Poly I:C treated human liver organoids exhibit morphology and genetic signature highly compatible to organoids developed from liver samples collected from BA patients. They are potential research materials to study
immune-mediated inflammation in BA.re |
Description | Poster presentation no. 1973 |
Persistent Identifier | http://hdl.handle.net/10722/315563 |
ISSN | 2023 Impact Factor: 12.9 2023 SCImago Journal Rankings: 5.011 |
DC Field | Value | Language |
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dc.contributor.author | Chung, HY | - |
dc.contributor.author | Lui, VCH | - |
dc.contributor.author | Wong, KKY | - |
dc.contributor.author | Tam, PKH | - |
dc.date.accessioned | 2022-08-19T09:00:13Z | - |
dc.date.available | 2022-08-19T09:00:13Z | - |
dc.date.issued | 2021 | - |
dc.identifier.citation | AASLD 2021: The Liver Meeting (Virtual), 12-15 November 2021. In Hepatology, v. 74 n. 1, p. 1173A | - |
dc.identifier.issn | 0270-9139 | - |
dc.identifier.uri | http://hdl.handle.net/10722/315563 | - |
dc.description | Poster presentation no. 1973 | - |
dc.description.abstract | Background: Biliary atresia (BA) is congenital disorder characterized by immune-mediated inflammation of the biliary systems resulting in life-threatening cholangiopathy In recent years, organoid technology has opened a new avenue for research in hepatobiliary diseases. Yet, the rarity of BA has limited the availability of human samples In this study, we explore the feasibility of creating a BA-like organoid by treating organoids from normal liver with Polyinosinic:Polycytidylic acid [Poly (I:C)], a synthetic immunostimulant that is structurally similar to a double-stranded RNA in virus Methods: BA organoids were developed from liver parenchyma collected during Kasai portoenterostomy Control organoids were developed from the non-tumor part of hepatoblastoma and they were co-cultured with Poly I:C (40 µg/ml). The organoid morphology was compared on day 17 In addition, RNAsequencing were performed to determine the transcriptomic difference between these samples Results: Control organoids without any treatment developed into well-expanded spherical organoids with a single-cell layer of epithelial cells and a single vacuole inside In contrast, after Poly I:C treatment, majority of these organoids developed into an aberrant morphology with a high index of similarity to BA organoids which were multivacuole and/or unexpanded (Figure 1A) RNA-sequencing analysis revealed that 19 inflammatory genes were commonly expressed in both groups They were selected for conditional cluster analysis and several genes that are involved in immune-mediated signaling pathway (SOCS6, SOCS6 1, ARAF, CAMK2G, GNA1C, ITGA2, PRKACA, PTEN ) we found to have a distinct pattern of expression in the Poly I:C treated control organoids, resembling the expression profile in BA multi-vacuole and unexpanded organoids (p<0.05) (Figure 1B). Conclusion: Poly I:C treated human liver organoids exhibit morphology and genetic signature highly compatible to organoids developed from liver samples collected from BA patients. They are potential research materials to study immune-mediated inflammation in BA.re | - |
dc.language | eng | - |
dc.publisher | John Wiley & Sons, Inc. The Journal's web site is located at http://www.hepatology.org/ | - |
dc.relation.ispartof | Hepatology | - |
dc.rights | Submitted (preprint) Version This is the pre-peer reviewed version of the following article: [FULL CITE], which has been published in final form at [Link to final article using the DOI]. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Use of Self-Archived Versions. Accepted (peer-reviewed) Version This is the peer reviewed version of the following article: [FULL CITE], which has been published in final form at [Link to final article using the DOI]. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Use of Self-Archived Versions. | - |
dc.title | Polyinosinic: polycytidylic acid [Poly(I:C)] treated liver organoids as a research model for biliary atresia | - |
dc.type | Conference_Paper | - |
dc.identifier.email | Chung, HY: chungphy@hku.hk | - |
dc.identifier.email | Lui, VCH: vchlui@hku.hk | - |
dc.identifier.email | Wong, KKY: kkywong@hku.hk | - |
dc.identifier.email | Tam, PKH: paultam@HKUCC-COM.hku.hk | - |
dc.identifier.authority | Chung, HY=rp02002 | - |
dc.identifier.authority | Lui, VCH=rp00363 | - |
dc.identifier.authority | Wong, KKY=rp01392 | - |
dc.identifier.authority | Tam, PKH=rp00060 | - |
dc.identifier.hkuros | 336118 | - |
dc.identifier.volume | 74 | - |
dc.identifier.issue | 1 | - |
dc.identifier.spage | 1173A | - |
dc.identifier.epage | 1173A | - |
dc.publisher.place | United States | - |