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A dataset of definitive endoderm and hepatocyte differentiations from human induced pluripotent stem cells.

ABSTRACT: Hepatocytes are a major parenchymal cell type in the liver and play an essential role in liver function. Hepatocyte-like cells can be differentiated in vitro from induced pluripotent stem cells (iPSCs) via definitive endoderm (DE)-like cells and hepatoblast-like cells. Here, we explored the in vitro differentiation time-course of hepatocyte-like cells. We performed methylome and transcriptome analyses for hepatocyte-like cell differentiation. We also analyzed DE-like cell differentiation by methylome, transcriptome, chromatin accessibility, and GATA6 binding profiles, using finer time-course samples. In this manuscript, we provide a detailed description of the dataset and the technical validations. Our data may be valuable for the analysis of the molecular mechanisms underlying hepatocyte and DE differentiations.

SUBMITTER: Tanaka Y

PROVIDER: S-EPMC9929325 | biostudies-literature | 2023 Feb

REPOSITORIES: biostudies-literature

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A dataset of definitive endoderm and hepatocyte differentiations from human induced pluripotent stem cells.

Tanaka Yuki Y Furuhata Erina E Maeda Shiori S Kishima Mami M Suzuki Harukazu H Suzuki Takahiro T

Scientific data 20230214 1

Hepatocytes are a major parenchymal cell type in the liver and play an essential role in liver function. Hepatocyte-like cells can be differentiated in vitro from induced pluripotent stem cells (iPSCs) via definitive endoderm (DE)-like cells and hepatoblast-like cells. Here, we explored the in vitro differentiation time-course of hepatocyte-like cells. We performed methylome and transcriptome analyses for hepatocyte-like cell differentiation. We also analyzed DE-like cell differentiation by meth ...[more]

PMID: 36788249

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Project description:Cellular organelles play fundamental roles in almost all cell behaviors. Mitochondria have been reported to be functionally linked to various biological processes, including reprogramming and pluripotency maintenance. However, very little about the role of mitochondria has been revealed in human early development and lineage specification. Here, we reported the characteristics and function of mitochondria during human definitive endoderm differentiation. Using a well-established differentiation system, we first investigated the change of mitochondrial morphology by comparing undifferentiated pluripotent stem cells, the intermediate mesendoderm cells, and differentiated endoderm cells, and found that mitochondria were gradually elongated and matured along differentiation. We further analyzed the expression pattern of mitochondria-related genes by RNA-seq, indicating that mitochondria became active during differentiation. Supporting this notion, the production of adenosine triphosphate (ATP) and reactive oxygen species (ROS) was increased as well. Functionally, we utilized chemicals and genome editing techniques, which could interfere with mitochondrial homeostasis, to determine the role of mitochondria in human endoderm differentiation. Treatment with mitochondrial inhibitors, or genetic depletion of mitochondrial transcription factor A (TFAM), significantly reduced the differentiation efficiency of definitive endoderm. In addition, the defect in endoderm differentiation due to dysfunctional mitochondria could be restored to some extent by the addition of ATP. Moreover, the clearance of excessive ROS due to dysfunctional mitochondria by N-acetylcysteine (NAC) improved the differentiation as well. We further found that ATP and NAC could partially replace the growth factor activin A for definitive endoderm differentiation. Our study illustrates the essential role of mitochondria during human endoderm differentiation through providing ATP and regulating ROS levels, which may provide new insight for metabolic regulation of cell fate determination.

Dataset Information

A dataset of definitive endoderm and hepatocyte differentiations from human induced pluripotent stem cells.

Publications

A dataset of definitive endoderm and hepatocyte differentiations from human induced pluripotent stem cells.

Similar Datasets

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