Human induced pluripotent stem cell derived hepatocytes provide insights on parenteral nutrition associated cholestasis in the immature liver

Abstract Parenteral nutrition-associated cholestasis (PNAC) significantly limits the safety of intravenous parenteral nutrition (PN). Critically ill infants are highly vulnerable to PNAC-related morbidity and mortality, however the impact of hepatic immaturity on PNAC is poorly understood. We examin...

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Autores principales:	T. Hang Nghiem-Rao, Courtney Pfeifer, Michelle Asuncion, Joshua Nord, Daniel Schill, Kirthi Pulakanti, Shailendra B. Patel, Lisa A. Cirillo, Sridhar Rao
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/b34671d9c6c646bb8f69da0849e3d014
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spelling	oai:doaj.org-article:b34671d9c6c646bb8f69da0849e3d0142021-12-02T15:03:07ZHuman induced pluripotent stem cell derived hepatocytes provide insights on parenteral nutrition associated cholestasis in the immature liver10.1038/s41598-021-90510-12045-2322https://doaj.org/article/b34671d9c6c646bb8f69da0849e3d0142021-06-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-90510-1https://doaj.org/toc/2045-2322Abstract Parenteral nutrition-associated cholestasis (PNAC) significantly limits the safety of intravenous parenteral nutrition (PN). Critically ill infants are highly vulnerable to PNAC-related morbidity and mortality, however the impact of hepatic immaturity on PNAC is poorly understood. We examined developmental differences between fetal/infant and adult livers, and used human induced pluripotent stem cell-derived hepatocyte-like cells (iHLC) to gain insights into the contribution of development to altered sterol metabolism and PNAC. We used RNA-sequencing and computational techniques to compare gene expression patterns in human fetal/infant livers, adult liver, and iHLC. We identified distinct gene expression profiles between the human feta/infant livers compared to adult liver, and close resemblance of iHLC to human developing livers. Compared to adult, both developing livers and iHLC had significant downregulation of xenobiotic, bile acid, and fatty acid metabolism; and lower expression of the sterol metabolizing gene ABCG8. When challenged with stigmasterol, a plant sterol found in intravenous soy lipids, lipid accumulation was significantly higher in iHLC compared to adult-derived HepG2 cells. Our findings provide insights into altered bile acid and lipid metabolizing processes in the immature human liver, and support the use of iHLC as a relevant model system of developing liver to study lipid metabolism and PNAC.T. Hang Nghiem-RaoCourtney PfeiferMichelle AsuncionJoshua NordDaniel SchillKirthi PulakantiShailendra B. PatelLisa A. CirilloSridhar RaoNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-12 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q T. Hang Nghiem-Rao Courtney Pfeifer Michelle Asuncion Joshua Nord Daniel Schill Kirthi Pulakanti Shailendra B. Patel Lisa A. Cirillo Sridhar Rao Human induced pluripotent stem cell derived hepatocytes provide insights on parenteral nutrition associated cholestasis in the immature liver
description	Abstract Parenteral nutrition-associated cholestasis (PNAC) significantly limits the safety of intravenous parenteral nutrition (PN). Critically ill infants are highly vulnerable to PNAC-related morbidity and mortality, however the impact of hepatic immaturity on PNAC is poorly understood. We examined developmental differences between fetal/infant and adult livers, and used human induced pluripotent stem cell-derived hepatocyte-like cells (iHLC) to gain insights into the contribution of development to altered sterol metabolism and PNAC. We used RNA-sequencing and computational techniques to compare gene expression patterns in human fetal/infant livers, adult liver, and iHLC. We identified distinct gene expression profiles between the human feta/infant livers compared to adult liver, and close resemblance of iHLC to human developing livers. Compared to adult, both developing livers and iHLC had significant downregulation of xenobiotic, bile acid, and fatty acid metabolism; and lower expression of the sterol metabolizing gene ABCG8. When challenged with stigmasterol, a plant sterol found in intravenous soy lipids, lipid accumulation was significantly higher in iHLC compared to adult-derived HepG2 cells. Our findings provide insights into altered bile acid and lipid metabolizing processes in the immature human liver, and support the use of iHLC as a relevant model system of developing liver to study lipid metabolism and PNAC.
format	article
author	T. Hang Nghiem-Rao Courtney Pfeifer Michelle Asuncion Joshua Nord Daniel Schill Kirthi Pulakanti Shailendra B. Patel Lisa A. Cirillo Sridhar Rao
author_facet	T. Hang Nghiem-Rao Courtney Pfeifer Michelle Asuncion Joshua Nord Daniel Schill Kirthi Pulakanti Shailendra B. Patel Lisa A. Cirillo Sridhar Rao
author_sort	T. Hang Nghiem-Rao
title	Human induced pluripotent stem cell derived hepatocytes provide insights on parenteral nutrition associated cholestasis in the immature liver
title_short	Human induced pluripotent stem cell derived hepatocytes provide insights on parenteral nutrition associated cholestasis in the immature liver
title_full	Human induced pluripotent stem cell derived hepatocytes provide insights on parenteral nutrition associated cholestasis in the immature liver
title_fullStr	Human induced pluripotent stem cell derived hepatocytes provide insights on parenteral nutrition associated cholestasis in the immature liver
title_full_unstemmed	Human induced pluripotent stem cell derived hepatocytes provide insights on parenteral nutrition associated cholestasis in the immature liver
title_sort	human induced pluripotent stem cell derived hepatocytes provide insights on parenteral nutrition associated cholestasis in the immature liver
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/b34671d9c6c646bb8f69da0849e3d014
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Human induced pluripotent stem cell derived hepatocytes provide insights on parenteral nutrition associated cholestasis in the immature liver

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