Noncoding RNA Transcripts during Differentiation of Induced Pluripotent Stem Cells into Hepatocytes.

Aniela Skrzypczyk,Stephan H Bernhart,Ilona Krystel,Augustinus Bader,Stephanie Kehr,Peter F Stadler,Shibashish Giri

doi:10.1155/2018/5692840

Abstract

Recent advances in the stem cell field allow to obtain many human tissues in vitro. However, hepatic differentiation of induced pluripotent stem cells (iPSCs) still remains challenging. Hepatocyte-like cells (HLCs) obtained after differentiation resemble more fetal liver hepatocytes. MicroRNAs (miRNA) play an important role in the differentiation process. Here, we analysed noncoding RNA profiles from the last stages of differentiation and compare them to hepatocytes. Our results show that HLCs maintain an epithelial character and express miRNA which can block hepatocyte maturation by inhibiting the epithelial-mesenchymal transition (EMT). Additionally, we identified differentially expressed small nucleolar RNAs (snoRNAs) and discovered novel noncoding RNA (ncRNA) genes.

Highlights

Human induced pluripotent stem cells (iPSCs) technology provides a powerful tool for both regenerative medicine and development analysis
Our results show that Hepatocyte-like cells (HLCs) maintain an epithelial character and express miRNA which can block hepatocyte maturation by inhibiting the epithelialmesenchymal transition (EMT)
The HLCs had the potential to store glycogen (PAS staining) (Figure 1(c)) and were able to metabolise indocyanine green (ICG) (Figure 1(d)), both functions being specific to liver tissue, indicating successful differentiation

Summary

Introduction

Human iPSC technology provides a powerful tool for both regenerative medicine and development analysis. Stem cells hold the potential to recapitulate embryonic differentiation of many tissues in vitro. Differentiated cells can replace damaged or degenerated cells in vivo (reviewed by [1, 2]). The liver is a complex organ with a high variety of functions. It is essential for detoxification and bile production. End-stage liver diseases are associated with hepatocyte apoptosis [3]. There is no possible compensation for liver failure. The only option to survive is through liver transplant, which is limited due to organ shortage. IPSCs could potentially be the source of cells for

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