Global Gene Expression Profiling Reveals Isorhamnetin Induces Hepatic-Lineage Specific Differentiation in Human Amniotic Epithelial Cells

Uchida, Yoshiaki; Ferdousi, Farhana; Zheng, Yun‐Wen; Oda, Tatsuya; Isoda, Hiroko

doi:10.3389/fcell.2020.578036

Cited by 12 publications

(14 citation statements)

References 76 publications

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“…Natural bioactive compounds have great potential to induce the targeted differentiation of stem cells in a lineage-specific manner by modulating cellular behavior and early biological and molecular events; however, only a handful of studies explored it. In our previous studies, we have reported that a caffeic acid ester (rosmarinic acid), a caffeoylquinic acid derivative (TCQA), and an iridoid glycoside (verbenalin) directed the differentiation of hAECs towards neuronal-lineage, whereas a flavonol aglycone isorhamnetin induced hepatic-lineage specific differentiation in hAECs [ 8 , 9 , 10 , 11 ]. We assume that other compounds from the anthocyanin group may have a similar effect as Cy3G on hAEC’s fate choice.…”

Section: Discussionmentioning

confidence: 99%

“…Recently, we have reported that verbenalin, a kind of phytochemical, has exerted therapeutic potential for Alzheimer's disease in hAECs [8]. Microarray gene expression profiling showed that rosmarinic acid-and isorhamnetintreated hAECs exerted neuronal and hepatic-lineage specific differentiation potential respectively [9,10]. A caffeoylquinic acid derivative, namely 3,4,5-Tri-O-Caffeoylquinic Acid, has also enhanced neural and pigment cell differentiation in hAECs [11].…”

Section: Introductionmentioning

confidence: 99%

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Human Amniotic Epithelial Cells as a Tool to Investigate the Effects of Cyanidin 3-O-Glucoside on Cell Differentiation

Takahashi

Ferdousi

Zheng

et al. 2021

IJMS

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Cyanidin, a kind of anthocyanin, has been reported to have chemotherapeutic activities in humans. Human amniotic epithelial cells (hAECs) are considered a potential source of pluripotent stem cells. hAECs have been used as a novel tool in regenerative cellular therapy and cell differentiation studies. In this study, to explore the effects of cyanidin-3-O-glucoside (Cy3G) on hAECs and their mechanisms, we investigated the transcriptomic changes in the Cy3G-treated cells using microarray analysis. Among the differentially expressed genes (Fold change > 1.1; p-value < 0.05), 109 genes were upregulated and 232 were downregulated. Ratios of upregulated and downregulated genes were 0.22% and 0.47% of the total expressed genes, respectively. Next, we explored the enriched gene ontology, i.e., the biological process, molecular function, and cellular component of the 37 upregulated (>1.3-fold change) and 124 downregulated (<1.3-fold change) genes. Significantly enriched biological processes by the upregulated genes included “response to muscle activity,” and the genes involved in this gene ontology (GO) were Metrnl and SRD5A1, which function in the adipocyte. On the other hand, the cell cycle biological process was significantly enriched by the downregulated genes, including some from the SMC gene family. An adipogenesis-associated gene DDX6 was also included in the cell cycle biological process. Thus, our findings suggest the prospects of Cy3G in modulating adipocyte differentiation in hAECs.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Human Amniotic Epithelial Cells as a Tool to Investigate the Effects of Cyanidin 3-O-Glucoside on Cell Differentiation

Takahashi

Ferdousi

Zheng

et al. 2021

IJMS

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“…Recently, the use of plant-based natural products that may affect the differentiation of stem cells has been approved in the mainstream of medicine because of their high availability, minimum toxicity, and low secondary effects [ 16 , 17 ]. It has been reported that different natural compounds may regulate early biological events in hAECs to induce directed differentiation such as rosmarinic acid induced neuronal differentiation, whereas isorhamnetin induced hepatic-lineage specific differentiation in hAECs [ 18 , 19 ]. Also, verbenalin-treated hAECs revealed a therapeutic potential for Alzheimer’s disease [ 20 ].…”

Section: Introductionmentioning

confidence: 99%

Regulating cell fate of human amnion epithelial cells using natural compounds: an example of enhanced neural and pigment differentiation by 3,4,5-tri-O-caffeoylquinic acid

et al. 2021

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Over the past years, Human Amnion Epithelial Cells (hAECs), a placental stem cell, are gaining higher attention from the scientific community as they showed several advantages over other types of stem cells, including availability, easy accessibility, reduced rejection rate, non-tumorigenicity, and minimal legal constraint. Recently, natural compounds are used to stimulate stem cell differentiation and proliferation and to enhance their disease-treating potential. A polyphenolic compound 3,4,5-Tri-O-Caffeoylquinic Acid (TCQA) has been previously reported to induce human neural stem cell differentiation and may affect melanocyte stem cell differentiation as well. In this study, TCQA was tested on 3D cultured hAECs after seven days of treatment, and then, microarray gene expression profiling was conducted of TCQA-treated and untreated control cells on day 0 and day 7. Analyses revealed that TCQA treatment significantly enriched pigment and neural cells sets; besides, genes linked with neurogenesis, oxidation–reduction process, epidermal development, and metabolism were positively regulated. Interestingly, TCQA stimulated cell cycle arrest-related pathways and differentiation signaling. On the other hand, TCQA decreased interleukins and cytokines expression and this due to its anti-inflammatory properties as a polyphenolic compound. Results were validated to highlight the main activities of TCQA on hAECs, including differentiation, cell cycle arrest, and anti-inflammatory. This study highlights the important role of hAECs in regenerative medicine and the use of natural compounds to regulate their fate.

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“…However, because of its stem cell-like properties, it can be used for the initial screening of target compounds. We have previously explored antifibrotic [ 71 ] and hepatic differentiation-inducing [ 170 ] potential of isorhamnetin in hAECs. In the present study, we have performed a targeted secondary analysis of our previously published data [ 71 ] to explore the potential functionalities of isorhamnetin in diabetes ( Figure 4 ).…”

Section: A Post Hoc Transcriptome Analysis Predicts the Potential Effect Of The Isorhamnetin On Diabetes In A Stem Cell-based Toolmentioning

confidence: 99%

“…A total of 303 DEGs were identified; among them, 60 were upregulated and 243 were downregulated. Details of methodology have been explained elsewhere [ 71 , 170 ]. All microarray data are available at Gene Expression Omnibus (GEO) under accession number: GSE153149 ( , accessed on 24 November 2021).…”

Section: A Post Hoc Transcriptome Analysis Predicts the Potential Effect Of The Isorhamnetin On Diabetes In A Stem Cell-based Toolmentioning

confidence: 99%

Effects of Isorhamnetin on Diabetes and Its Associated Complications: A Review of In Vitro and In Vivo Studies and a Post Hoc Transcriptome Analysis of Involved Molecular Pathways

Kalai

Boulaaba

Ferdousi

et al. 2022

IJMS

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Diabetes mellitus, especially type 2 (T2DM), is a major public health problem globally. DM is characterized by high levels of glycemia and insulinemia due to impaired insulin secretion and insulin sensitivity of the cells, known as insulin resistance. T2DM causes multiple and severe complications such as nephropathy, neuropathy, and retinopathy causing cell oxidative damages in different internal tissues, particularly the pancreas, heart, adipose tissue, liver, and kidneys. Plant extracts and their bioactive phytochemicals are gaining interest as new therapeutic and preventive alternatives for T2DM and its associated complications. In this regard, isorhamnetin, a plant flavonoid, has long been studied for its potential anti-diabetic effects. This review describes its impact on reducing diabetes-related disorders by decreasing glucose levels, ameliorating the oxidative status, alleviating inflammation, and modulating lipid metabolism and adipocyte differentiation by regulating involved signaling pathways reported in the in vitro and in vivo studies. Additionally, we include a post hoc whole-genome transcriptome analysis of biological activities of isorhamnetin using a stem cell-based tool.

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Global Gene Expression Profiling Reveals Isorhamnetin Induces Hepatic-Lineage Specific Differentiation in Human Amniotic Epithelial Cells

Cited by 12 publications

References 76 publications

Human Amniotic Epithelial Cells as a Tool to Investigate the Effects of Cyanidin 3-O-Glucoside on Cell Differentiation

Human Amniotic Epithelial Cells as a Tool to Investigate the Effects of Cyanidin 3-O-Glucoside on Cell Differentiation

Regulating cell fate of human amnion epithelial cells using natural compounds: an example of enhanced neural and pigment differentiation by 3,4,5-tri-O-caffeoylquinic acid

Effects of Isorhamnetin on Diabetes and Its Associated Complications: A Review of In Vitro and In Vivo Studies and a Post Hoc Transcriptome Analysis of Involved Molecular Pathways

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