A Descriptive Whole-Genome Transcriptomics Study in a Stem Cell-Based Tool Predicts Multiple Tissue-Specific Beneficial Potential and Molecular Targets of Carnosic Acid
Abstract
:1. Introduction
2. Results
2.1. Carnosic Acid Significantly Regulated Gene Expression in hAESCs
2.2. Carnosic Acid Biased hAESCs toward Mesodermal Lineage Progression
2.3. Carnosic Acid Regulated a Wide Range of Biological and Molecular Events in hAESCs
2.4. Carnosic-Acid-Regulated Germ-Layer-Specific Pathways in hAESCs
2.5. Protein–Protein Interaction Network Topography in Carnosic Acid-Treated hAESCs
2.6. Significantly Enriched Transcription Factors and Kinases in Carnosic-Acid-Treated hAESCs
2.7. Chemical and Disease Perturbation Enrichment Analyses by the DEGs in Carnosic Acid-Treated hAESCs
3. Discussion
4. Materials and Methods
4.1. hAESCs Isolation and Cell Culture Maintenance
4.2. Preparation of 3D Spheroid Formation and Cell Treatment
4.3. RNA Extraction and Quantification
4.4. DNA Microarray Analysis
4.5. Microarray Data Processing and Quality Control
4.6. Microarray Data Analysis
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Gene Symbol | Description | Fold Change | p Value | Biological Functions |
---|---|---|---|---|
AKR1C1 | aldo-keto reductase family 1, member C1 | 33.45 | 2.14 × 10−7 | bile acid and bile salt transport and metabolic process, cholesterol homeostasis, Metabolism of fat-soluble vitamins, lipids and lipoproteins, and xenobiotics by cytochrome P450 |
PTX3 | pentraxin 3, long | 20.74 | 7.75 × 10−6 | extracellular matrix organization, innate immune response, negative regulation by host of viral exo-alpha-sialidase activity, |
TNFRSF9 | tumor necrosis factor receptor superfamily, member 9 | 19.12 | 4.78 × 10−6 | negative regulation of IL10 and IL12 production, TNFR2 non-canonical NFkB pathway |
AKR1C2 | aldo-keto reductase family 1, member C2 | 18.53 | 5.38 × 10−7 | G protein-coupled receptor signaling pathway, positive regulation of protein kinase B signaling, Bile acid and bile salt metabolism |
AKR1B1 | aldo-keto reductase family 1, member B1 (aldose reductase) | 16.18 | 1.38 × 10−7 | C21-steroid hormone biosynthetic process, negative regulation of apoptotic process, positive regulation of JAK–STAT cascade, positive regulation of smooth muscle cell proliferation |
TM4SF1 | transmembrane 4 L six family member 1 | 16.11 | 5.96 × 10−7 | plasma membrane component |
SLC7A11 | solute carrier family 7 (anionic amino acid transporter light chain, xc- system), member 11 | 13.89 | 2.78 × 10−7 | brain development, adult locomotory behavior, cellular response to oxidative stress |
ABI3BP | ABI family, member 3 (NESH) binding protein | 13.29 | 4.78 × 10−7 | defense response to tumor cell, extracellular matrix organization, negative regulation of cell proliferation, negative regulation of connective tissue replacement involved in inflammatory response wound healing, positive regulation of cardiocyte differentiation, gene expression decreases in aging skin |
ANKRD1 | ankyrin repeat domain 1 (cardiac muscle) | 12.1 | 1.63 × 10−6 | cardiac muscle tissue morphogenesis, myoblast differentiation, cellular response to IL1, TGFβ, and TNF stimulus, Regulation of lipid metabolism by PPARα |
ABCG1 | ATP binding cassette subfamily G member 1 | 12.1 | 1.08 × 10−5 | amyloid precursor protein catabolic process, positive regulation of Aβ formation (suppress), cholesterol efflux, cellular response to HDL particle stimulus, negative regulation of macrophage-derived foam cell differentiation |
Gene Symbol | Description | Fold Change | p Value | Biological Functions |
---|---|---|---|---|
HAS1S1 | hyaluronan synthase 1 | −45.45 | 2.64 × 10−6 | A major component of extracellular matrix that regulates cell adhesion, migration, and differentiation. It is expressed in mesenchymal cells, such as astrocytes in the CNS and fibroblasts in heart, negative regulation of fibroblast migration, cellular response to platelet-derived growth factor stimulus. Stroke induces the expression of HAS1 |
GUCY1A3 | guanylate cyclase 1, soluble, alpha 3 | −44.58 | 3.9 × 10−6 | a key enzyme in the nitric oxide/cGMP signaling pathway, inhibits platelet aggregation upon stimulation with nitric oxide |
PRLR | prolactin receptor | −44.08 | 3.24 × 10−8 | Prolactin signaling pathway, activation of JAK–STAT cascade, PI3K–Akt signaling pathway, leukemia inhibitory factor signaling pathway, highly expressed in depression (rat model, brain), in breast and cervical cancer cells |
COMP | cartilage oligomeric matrix protein | −37.75 | 2.81 × 10−8 | blood coagulation, Focal adhesion, collagen fibril organization, chondrocyte proliferation, BMP signaling pathway, PI3K–Akt signaling pathway, upregulates in cardiac fibrosis and osteoarthritis |
AQP1 | aquaporin 1 (Colton blood group) | −34.66 | 3.15 × 10−8 | cellular response to cAMP and to hypoxia, O2/CO2 exchange in erythrocytes, induces angiotensin II-induced cardiac hypertrophy, increases the risk of myocardial infarction |
IGFBP5 | Insulin-like growth factor binding protein 5 | −34.08 | 1.48 × 10−6 | Promotes fibrosis and increases the risk of cardiovascular disease, causes abnormal curvature and thinning of the hair shaft, induces IL6-mediated ROS production, and causes premature cell senescence |
CILP | cartilage intermediate layer protein, nucleotide pyrophosphohydrolase | −28.63 | 2.7 × 10−5 | cellular response to TGFβ, negative regulation of insulin-like growth factor receptor signaling pathway, CILP combines with TGFβ or IGF1 to regulate the ECM synthesis in cartilage and promotes degeneration and aging progress in intervertebral discs (IVDs) (but CILP inhibits cardiac fibrosis). |
LRRC32 | Leucine-rich repeat containing 32 | −26.39 | 4.46 × 10−8 | TGFβ receptor signaling pathway, negative regulation of activated T cell proliferation |
CHI3L1 | chitinase 3-like 1 (cartilage glycoprotein-39) | −25.56 | 4.97 × 10−7 | It plays a major role in tissue injury, inflammation, tissue repair, and remodeling responses and has been strongly associated with diseases including asthma, arthritis, sepsis, diabetes, liver fibrosis, coronary artery disease, cancer invasion, and metastasis. |
SLC7A8 | solute carrier family 7 (amino acid transporter light chain, L system), member 8 | −24.35 | 8.9 × 10−8 | amino acid transmembrane transport |
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Ferdousi, F.; Sasaki, K.; Fukumitsu, S.; Kuwata, H.; Nakajima, M.; Isoda, H. A Descriptive Whole-Genome Transcriptomics Study in a Stem Cell-Based Tool Predicts Multiple Tissue-Specific Beneficial Potential and Molecular Targets of Carnosic Acid. Int. J. Mol. Sci. 2023, 24, 8077. https://doi.org/10.3390/ijms24098077
Ferdousi F, Sasaki K, Fukumitsu S, Kuwata H, Nakajima M, Isoda H. A Descriptive Whole-Genome Transcriptomics Study in a Stem Cell-Based Tool Predicts Multiple Tissue-Specific Beneficial Potential and Molecular Targets of Carnosic Acid. International Journal of Molecular Sciences. 2023; 24(9):8077. https://doi.org/10.3390/ijms24098077
Chicago/Turabian StyleFerdousi, Farhana, Kazunori Sasaki, Satoshi Fukumitsu, Hidetoshi Kuwata, Mitsutoshi Nakajima, and Hiroko Isoda. 2023. "A Descriptive Whole-Genome Transcriptomics Study in a Stem Cell-Based Tool Predicts Multiple Tissue-Specific Beneficial Potential and Molecular Targets of Carnosic Acid" International Journal of Molecular Sciences 24, no. 9: 8077. https://doi.org/10.3390/ijms24098077