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Description
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The dataset contains high-throughput mRNA sequencing reads (FASTA files, extension .fq.gz) of human pluripotent stem cell-derived hepatic stellate cells (scHSCs). The sequencing was performed by the Novogene UK Cambridge Sequencing Center.
Hepatic stellate cells (HSCs) are hepatic pericytes. They exist in a quiescent state during homeostasis and transdifferentiate to an activated state during liver injury and disease. In the activated state, the HSCs are described as losing their vitamin A-storing lipid droplets.
Transforming growth factor beta 1 (TGF-b) is a potent activator of HSCs. Starvation of vitamin A (retinol) and lipid (palmitic acid) media supplementation has also been proposed to affect the HSC activation status.
In this dataset, the mRNA of scHSCs derived from four different human pluripotent stem cell (hPSC) lines were sequenced by Novogene (see https://www.novogene.com/eu-en/). scHSCs from all hPSC lines were divided into four groups, each performed in technical triplicates, and treated for 48 hours to assess activation-related changes to the transcriptomes. The project aimed at providing novel information on the relationship between scHSC activation and vitamin A and lipids.
The scHSCs treatments were:
- "Control", meaning no treatment.
- "Starvation", meaning starvation of retinol and palmitic acid media supplementation.
- "TGFb", meaning treatment with 25 ng/mL TGF-b.
- "Starvation + TGFb", combining the "Starvation" and "TGFb" treatments. (2024-06-07)
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Related Publication
| AUTHOR=Wilhelmsen Ingrid, Combriat Thomas, Dalmao-Fernandez Andrea, Stokowiec Justyna, Wang Chencheng, Olsen Petter Angell, Wik Jonas Aakre, Boichuck Yuliia, Aizenshtadt Aleksandra, Krauss Stefan
TITLE=The effects of TGF-β-induced activation and starvation of vitamin A and palmitic acid on human stem cell-derived hepatic stellate cells
JOURNAL=Stem Cell Research & Therapy
VOLUME=15
YEAR=2024
URL=https://stemcellres.biomedcentral.com/articles/10.1186/s13287-024-03852-8
DOI=10.1186/s13287-024-03852-8
ISSN=1757-6512
ABSTRACT=Background: Hepatic stellate cells (HSC) have numerous critical roles in liver function and homeostasis, while they are also known for their importance during liver injury and fibrosis. There is therefore a need for relevant in vitro human HSC models to fill current knowledge gaps. In particular, the roles of vitamin A (VA), lipid droplets (LDs), and energy metabolism in human HSC activation are poorly understood. Methods: In this study, human pluripotent stem cell-derived HSCs (scHSCs), benchmarked to human primary HSC, were exposed to 48-hour starvation of retinol (ROL) and palmitic acid (PA) in the presence or absence of the potent HSC activator TGF-β. The interventions were studied by an extensive set of phenotypic and functional analyses, including transcriptomic analysis, measurement of activation-related proteins and cytokines, VA- and LD storage, and cell energy metabolism. Results: The results show that though the starvation of ROL and PA alone did not induce scHSC activation, the starvation amplified the TGF-β-induced activation-related transcriptome. However, TGF-β-induced activation alone did not lead to a reduction in VA or LD stores. Additionally, reduced glycolysis and increased mitochondrial fission were observed in response to TGF-β. Conclusions: scHSCs are robust models for activation studies. The loss of VA and LDs is not sufficient for scHSC activation in vitro, but may amplify the TGF-β-induced activation response. Collectively, our work provides an extensive framework for studying human HSCs in healthy and diseased conditions.
doi: 10.1186/s13287-024-03852-8 |
