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J Biomol Screen DOI:10.1177/1087057116660277

High-Throughput Platform for Identifying Molecular Factors Involved in Phenotypic Stabilization of Primary Human Hepatocytes In Vitro.

Publication TypeJournal Article
Year of Publication2016
AuthorsShan, J, Logan, DJ, Root, DE, Carpenter, AE, Bhatia, SN
JournalJ Biomol Screen
Volume21
Issue9
Pages897-911
Date Published2016 Oct
ISSN1552-454X
Abstract

Liver disease is a leading cause of morbidity worldwide and treatment options are limited, with organ transplantation being the only form of definitive management. Cell-based therapies have long held promise as alternatives to whole-organ transplantation but have been hindered by the rapid loss of liver-specific functions over a period of days in cultured hepatocytes. Hypothesis-driven studies have identified a handful of factors that modulate hepatocyte functions in vitro, but our understanding of the mechanisms involved remains incomplete. We thus report here the development of a high-throughput platform to enable systematic interrogation of liver biology in vitro. The platform is currently configured to enable genetic knockdown screens and includes an enzyme-linked immunosorbent assay-based functional assay to quantify albumin output as a surrogate marker for hepatocyte synthetic functions as well as an image-based viability assay that counts hepatocyte nuclei. Using this platform, we identified 12 gene products that may be important for hepatocyte viability and/or liver identity in vitro. These results represent important first steps in the elucidation of mechanisms instrumental to the phenotypic maintenance of hepatocytes in vitro, and we hope that the tools reported here will empower additional studies in various fields of liver research.

DOI10.1177/1087057116660277
Pubmed

http://www.ncbi.nlm.nih.gov/pubmed/27650791?dopt=Abstract

Alternate JournalJ Biomol Screen
PubMed ID27650791
Grant ListUH3 EB017103 / EB / NIBIB NIH HHS / United States