Extensive reprogramming of the nascent transcriptome during iPSC to hepatocyte differentiation

Autor: Henri Niskanen, Mikko Oittinen, Tommi Rantapero, Minna U. Kaikkonen, Keijo Viiri, Leena E. Viiri, Katriina Aalto-Setälä, Anna Alexanova, Matti Nykter, Mostafa Kiamehr
Přispěvatelé: Lääketieteen ja terveysteknologian tiedekunta - Faculty of Medicine and Health Technology, Tampere University
Rok vydání: 2019
Předmět:
Zdroj: Scientific Reports
Scientific Reports, Vol 9, Iss 1, Pp 1-12 (2019)
ISSN: 2045-2322
DOI: 10.1038/s41598-019-39215-0
Popis: Hepatocyte-like cells (HLCs) derived from induced pluripotent stem cells (iPSCs) provide a renewable source of cells for drug discovery, disease modelling and cell-based therapies. Here, by using GRO-Seq we provide the first genome-wide analysis of the nascent RNAs in iPSCs, HLCs and primary hepatocytes to extend our understanding of the transcriptional changes occurring during hepatic differentiation process. We demonstrate that a large fraction of hepatocyte-specific genes are regulated at transcriptional level and identify hundreds of differentially expressed non-coding RNAs (ncRNAs), including primary miRNAs (pri-miRNAs) and long non-coding RNAs (lncRNAs). Differentiation induced alternative transcription start site (TSS) usage between the cell types as evidenced for miR-221/222 and miR-3613/15a/16-1 clusters. We demonstrate that lncRNAs and coding genes are tightly co-expressed and could thus be co-regulated. Finally, we identified sets of transcriptional regulators that might drive transcriptional changes during hepatocyte differentiation. These included RARG, E2F1, SP1 and FOXH1, which were associated with the down-regulated transcripts, and hepatocyte-specific TFs such as FOXA1, FOXA2, HNF1B, HNF4A and CEBPA, as well as RXR, PPAR, AP-1, JUNB, JUND and BATF, which were associated with up-regulated transcripts. In summary, this study clarifies the role of regulatory ncRNAs and TFs in differentiation of HLCs from iPSCs. ispartof: SCIENTIFIC REPORTS vol:9 issue:1 ispartof: location:England status: published
Databáze: OpenAIRE
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