Abstract
Nonalcoholic fatty liver disease (NAFLD) is one of the leading causes of liver disease worldwide.1 Animal models are widely used to investigate the mechanisms of fatty liver disease, but they do not faithfully represent NAFLD in humans.2 Thus, there is strong interest in studying NAFLD pathogenesis directly in humans whenever possible. One strategy that is gaining momentum is to utilize iPSC-derived hepatocytes from individual human subjects in complex cell/organ platforms with the goal of reproducing a NAFLD-like state in vitro.3-6 Our group has taken a different approach, positing that iPSC-Heps from a population of NAFLD patients would provide independent insight into the human disease. In this study we generated iPSCs and iPSC-Heps from a well-defined cohort of NAFLD patients. Our objective was to determine whether as a group, in the absence of any metabolic challenge, they exhibit common disease-specific signatures that are distinct from healthy controls.
Competing Interest Statement
This work was funded by research grants from the California Institute for Regenerative Medicine (IT1-06563), AbbVie, Inc. and NIH: R21 DK118380 (JJM), UG3 DK120004 (HW) and K08 DK098270 (ANM). Additional support was provided by core facilities within the UCSF Liver Center (P30 DK026743).