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Extensive reprogramming of the nascent transcriptome during iPSC to hepatocyte differentiation
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 hepatoc...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6401154/ https://www.ncbi.nlm.nih.gov/pubmed/30837492 http://dx.doi.org/10.1038/s41598-019-39215-0 |
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author | Viiri, Leena E. Rantapero, Tommi Kiamehr, Mostafa Alexanova, Anna Oittinen, Mikko Viiri, Keijo Niskanen, Henri Nykter, Matti Kaikkonen, Minna U. Aalto-Setälä, Katriina |
author_facet | Viiri, Leena E. Rantapero, Tommi Kiamehr, Mostafa Alexanova, Anna Oittinen, Mikko Viiri, Keijo Niskanen, Henri Nykter, Matti Kaikkonen, Minna U. Aalto-Setälä, Katriina |
author_sort | Viiri, Leena E. |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-6401154 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-64011542019-03-07 Extensive reprogramming of the nascent transcriptome during iPSC to hepatocyte differentiation Viiri, Leena E. Rantapero, Tommi Kiamehr, Mostafa Alexanova, Anna Oittinen, Mikko Viiri, Keijo Niskanen, Henri Nykter, Matti Kaikkonen, Minna U. Aalto-Setälä, Katriina Sci Rep Article 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. Nature Publishing Group UK 2019-03-05 /pmc/articles/PMC6401154/ /pubmed/30837492 http://dx.doi.org/10.1038/s41598-019-39215-0 Text en © The Author(s) 2019 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Article Viiri, Leena E. Rantapero, Tommi Kiamehr, Mostafa Alexanova, Anna Oittinen, Mikko Viiri, Keijo Niskanen, Henri Nykter, Matti Kaikkonen, Minna U. Aalto-Setälä, Katriina Extensive reprogramming of the nascent transcriptome during iPSC to hepatocyte differentiation |
title | Extensive reprogramming of the nascent transcriptome during iPSC to hepatocyte differentiation |
title_full | Extensive reprogramming of the nascent transcriptome during iPSC to hepatocyte differentiation |
title_fullStr | Extensive reprogramming of the nascent transcriptome during iPSC to hepatocyte differentiation |
title_full_unstemmed | Extensive reprogramming of the nascent transcriptome during iPSC to hepatocyte differentiation |
title_short | Extensive reprogramming of the nascent transcriptome during iPSC to hepatocyte differentiation |
title_sort | extensive reprogramming of the nascent transcriptome during ipsc to hepatocyte differentiation |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6401154/ https://www.ncbi.nlm.nih.gov/pubmed/30837492 http://dx.doi.org/10.1038/s41598-019-39215-0 |
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