ArticleScientific reports2019
Extensive reprogramming of the nascent transcriptome during iPSC to hepatocyte differentiation.
Article in Scientific reports, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed, 25 citations in OpenAlex.
- Human iPSC-derived neural stem cells displaying radial glia signature exhibit long-term safety in mice.Nature communications · 2024Article
- Cooperative insulation of regulatory domains by CTCF-dependent physical insulation and promoter competition.Nature communications · 2024Article
- Comparative transcriptomic and phenotypic analysis of induced pluripotent stem cell hepatocyte-like cells and primary human hepatocytes.Cell and tissue research · 2024Article
- Photo-click hydrogels for 3D in situ differentiation of pancreatic progenitors from induced pluripotent stem cells.Stem cell research & therapy · 2023Article
- Hepatocyte Differentiation from iPSCs or MSCs in Decellularized Liver Scaffold: Cell-ECM Adhesion, Spatial Distribution, and Hepatocyte Maturation Profile.Organogenesis · 2022Article
- Global-run on sequencing identifiesiScience · 2022Article
- Targeting of noncoding RNAs encoded by a novel MYC enhancers inhibits the proliferation of human hepatic carcinoma cells in vitro.Scientific reports · 2022Article
- Genomic Landscapes of Noncoding RNAs RegulatingMolecular and cellular biology · 2021Article
- Interaction between LINC-ROR and Stemness State in Gastric Cancer Cells with Helicobacter pylori Infection.Iranian biomedical journal · 2021Article
- Microengineered systems with iPSC-derived cardiac and hepatic cells to evaluate drug adverse effects.Experimental biology and medicine (Maywood, N.J.) · 2021Review
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Authors and funding
10 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
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.
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