Profiling of derived-hepatocyte progenitors from induced pluripotent stem cells using nanoCAGE promoter analysis

Bernier, Myriam Lereau; Poulain, Stéphane; Tauran, Yannick; Danoy, Mathieu; Shinohara, Masanao; Kimura, Keiichi; Segard, Bertrand David; Kato, Sachi; Kido, Taketomo; Miyajima, Atsushi; Sakai, Yasuyuki; Plessy, Charles; Leclerc, Éric

doi:10.1016/j.bej.2018.11.001

Cited by 9 publications

(2 citation statements)

References 37 publications

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“…NanoCAGE sequencing libraries were prepared following the protocol described in Poulain et al (2017). Total RNA extraction and library preparation steps were performed as detailed in Lereau‐ Bernier et al (2019). The pool of nanoCAGE samples was sequenced paired‐end (9.13 pM + 10% PhiX) on the MiSeq system with the Reagent Kit v3 150‐cycles (Illumina).…”

Section: Methodsmentioning

confidence: 99%

“…Despite significant efforts toward an enhanced maturation hiPSCs‐derived (HLCs), primitiveness patterns are still largely observed (Hay et al, 2008; Kido et al, 2015; Lereau‐Bernier et al, 2019; Si‐Tayeb et al, 2010; Touboul et al, 2010,). Consequently, hiPSCs‐derived HLCs are still far from being in a state which would allow them to be used for in vitro studies in the industry.…”

Section: Introductionmentioning

confidence: 99%

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Multi‐omics analysis of hiPSCs‐derived HLCs matured on‐chip revealed patterns typical of liver regeneration

Danoy

Tauran

Poulain

et al. 2021

Biotech & Bioengineering

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Maturation of human‐induced pluripotent stem cells (hiPSCs)‐derived hepatocytes‐like cells (HLCs) toward a complete hepatocyte phenotype remains a challenge as primitiveness patterns are still commonly observed. In this study, we propose a modified differentiation protocol for those cells which includes a prematuration in Petri dishes and a maturation in microfluidic biochip. For the first time, a large range of biomolecular families has been extracted from the same sample to combine transcriptomic, proteomic, and metabolomic analysis. After integration, these datasets revealed specific molecular patterns and highlighted the hepatic regeneration profile in biochips. Overall, biochips exhibited processes of cell proliferation and inflammation (via TGFB1) coupled with anti‐fibrotic signaling (via angiotensin 1‐7, ATR‐2, and MASR). Moreover, cultures in this condition displayed physiological lipid‐carbohydrate homeostasis (notably via PPAR, cholesterol metabolism, and bile synthesis) coupled with cell respiration through advanced oxidative phosphorylation (through the overexpression of proteins from the third and fourth complex). The results presented provide an original overview of the complex mechanisms involved in liver regeneration using an advanced in vitro organ‐on‐chip technology.

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Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Multi‐omics analysis of hiPSCs‐derived HLCs matured on‐chip revealed patterns typical of liver regeneration

Danoy

Tauran

Poulain

et al. 2021

Biotech & Bioengineering

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Characterization of liver zonation‐like transcriptomic patterns in HLCs derived from hiPSCs in a microfluidic biochip environment

Danoy

Poulain

Lereau-Bernier

et al. 2020

Biotechnology Progress

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The liver zonation is an important phenomenon characterized by a gradient of several functions along the liver acinus. However, this gradient remains difficult to reproduce in in-vitro conditions, making the obtention of an in-vitro method to recapitulate the liver zonation a challenging issue. In this study, we evaluated the spatial evolution of the transcriptome profile of human induced pluripotent stem cells (hiPSCs) differentiated toward hepatocytes-like cells (HLCs) phenotype in a microfluidic biochip environment. Cells collected at the inlet of the biochip, where the oxygen concentration is higher, were identified by the expression of genes involved in metabolic pathways related to cellular reorganization and cell proliferation. Cells collected in the middle and at the outlet of the biochips, where oxygen concentrations are lower, were characterized by the upregulation of genes involved in cellular detoxification processes (CYP450), PPAR signaling or arginine biosynthesis. A subset of 16 transcription factors (TFs) was extracted and identified as upstream regulators to HNF1A and PPARA. These TFs are also known as regulators to target genes engaged in the Wnt/βcatenin pathway, in the TGFβ/BMP/SMAD signaling, in the transition between epithelial mesenchymal transition (EMT) and mesenchymal epithelial transition (MET), in the homeostasis of lipids, bile acids and carbohydrates homeostasis, in drug metabolism, in the estrogen processing and in the oxidative stress response. Overall, the analysis allowed to confirm a partial zonation-like pattern in hiPSCs-derived HLCs in the microfluidic biochip environment. These results provide important insights into the reproduction of liver zonation in-vitro for a better understanding of the phenomenon.

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Metabolomic profiling during the differentiation of human induced pluripotent stem cells into hepatocyte-like cells

et al. 2020

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Profiling of derived-hepatocyte progenitors from induced pluripotent stem cells using nanoCAGE promoter analysis

Cited by 9 publications

References 37 publications

Multi‐omics analysis of hiPSCs‐derived HLCs matured on‐chip revealed patterns typical of liver regeneration

Multi‐omics analysis of hiPSCs‐derived HLCs matured on‐chip revealed patterns typical of liver regeneration

Characterization of liver zonation‐like transcriptomic patterns in HLCs derived from hiPSCs in a microfluidic biochip environment

Metabolomic profiling during the differentiation of human induced pluripotent stem cells into hepatocyte-like cells

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