3,2'-Dihydroxyflavone Improves the Proliferation and Survival of Human Pluripotent Stem Cells and Their Differentiation into Hematopoietic Progenitor Cells

Overview

Journal J Clin Med

Specialty General Medicine

Date 2020 Mar 6

PMID 32131506

Citations 11

Authors

Kyeongseok Kim

Ahmed Abdal Dayem

Minchan Gil

Gwang-Mo Yang

Soo Bin Lee

Oh-Hyung Kwon

Sangbaek Choi

Geun-Ho Kang

Kyung Min Lim

Dongho Kim

Ssang-Goo Cho

Affiliations

Soon will be listed here.

Abstract

Efficient maintenance of the undifferentiated status of human pluripotent stem cells (hiPSCs) is crucial for producing cells with improved proliferation, survival and differentiation, which can be successfully used for stem cell research and therapy. Here, we generated iPSCs from healthy donor peripheral blood mononuclear cells (PBMCs) and analyzed the proliferation and differentiation capacities of the generated iPSCs using single cell NGS-based 24-chromosome aneuploidy screening and RNA sequencing. In addition, we screened various natural compounds for molecules that could enhance the proliferation and differentiation potential of hiPSCs. Among the tested compounds, 3,2'-dihydroxyflavone (3,2'-DHF) significantly increased cell proliferation and expression of naïve stemness markers and decreased the dissociation-induced apoptosis of hiPSCs. Of note, 3,2'-DHF-treated hiPSCs showed upregulation of intracellular glutathione (GSH) and an increase in the percentage of GSH-high cells in an analysis with a FreSHtracer system. Interestingly, culture of the 3,2'-DHF-treated hiPSCs in differentiation media enhanced their mesodermal differentiation and differentiation into CD34+ CD45+ hematopoietic progenitor cells (HPC) and natural killer cells (NK) cells. Taken together, our results demonstrate that the natural compound 3,2'-DHF can improve the proliferation and differentiation capacities of hiPSCs and increase the efficiency of HPC and NK cell production from hiPSCs.

Citing Articles

Antifungal and antibiofilm activities of flavonoids against : Focus on 3,2'-dihydroxyflavone as a potential therapeutic agent.

Lee J, Kim Y, Park I, Lee J Biofilm. 2024; 8:100218.

PMID: 39175909 PMC: 11340609. DOI: 10.1016/j.bioflm.2024.100218.

Antibiofilm and Antivirulence Potentials of 3,2'-Dihydroxyflavone against .

Park I, Kim Y, Lee J, Lee J Int J Mol Sci. 2024; 25(15).

PMID: 39125628 PMC: 11311418. DOI: 10.3390/ijms25158059.

Improving hematopoietic differentiation from human induced pluripotent stem cells by the modulation of Hippo signaling with a diarylheptanoid derivative.

Thongsa-Ad U, Wongpan A, Wongkummool W, Chaiwijit P, Uppakara K, Chaiyakitpattana G Stem Cell Res Ther. 2024; 15(1):60.

PMID: 38433217 PMC: 10910864. DOI: 10.1186/s13287-024-03686-4.

Selected flavonoids exhibit antibiofilm and antibacterial effects against by disrupting membrane integrity, virulence and metabolic activities.

Faleye O, Lee J, Lee J Biofilm. 2023; 6:100165.

PMID: 38034415 PMC: 10681883. DOI: 10.1016/j.bioflm.2023.100165.

A novel perfusion bioreactor promotes the expansion of pluripotent stem cells in a 3D-bioprinted tissue chamber.

Komosa E, Lin W, Mahadik B, Bazzi M, Townsend D, Fisher J Biofabrication. 2023; 16(1).

PMID: 37906964 PMC: 10636629. DOI: 10.1088/1758-5090/ad084a.

References

Wang K, Zhang T, Dong Q, Nice E, Huang C, Wei Y . Redox homeostasis: the linchpin in stem cell self-renewal and differentiation. Cell Death Dis. 2013; 4:e537. PMC: 3613828. DOI: 10.1038/cddis.2013.50. View

Cho C, Lee S, Lee G, Woo H, Choi E, Rhee S . Irreversible inactivation of glutathione peroxidase 1 and reversible inactivation of peroxiredoxin II by H2O2 in red blood cells. Antioxid Redox Signal. 2010; 12(11):1235-46. PMC: 2875961. DOI: 10.1089/ars.2009.2701. View

Marsboom G, Zhang G, Pohl-Avila N, Zhang Y, Yuan Y, Kang H . Glutamine Metabolism Regulates the Pluripotency Transcription Factor OCT4. Cell Rep. 2016; 16(2):323-332. PMC: 4945388. DOI: 10.1016/j.celrep.2016.05.089. View

Chang M, Rhee Y, Yi S, Lee S, Kim R, Kim H . Doxycycline enhances survival and self-renewal of human pluripotent stem cells. Stem Cell Reports. 2014; 3(2):353-64. PMC: 4175555. DOI: 10.1016/j.stemcr.2014.06.013. View

Lee E, Kim J, Kang Y, Ahn J, Kim J, Kim B . Interplay between PI3K/Akt and MAPK signaling pathways in DNA-damaging drug-induced apoptosis. Biochim Biophys Acta. 2006; 1763(9):958-68. DOI: 10.1016/j.bbamcr.2006.06.006. View

Young R . Control of the embryonic stem cell state. Cell. 2011; 144(6):940-54. PMC: 3099475. DOI: 10.1016/j.cell.2011.01.032. View

Gafni O, Weinberger L, AlFatah Mansour A, Manor Y, Chomsky E, Ben-Yosef D . Derivation of novel human ground state naive pluripotent stem cells. Nature. 2013; 504(7479):282-6. DOI: 10.1038/nature12745. View

Chen K, Mallon B, McKay R, Robey P . Human pluripotent stem cell culture: considerations for maintenance, expansion, and therapeutics. Cell Stem Cell. 2014; 14(1):13-26. PMC: 3915741. DOI: 10.1016/j.stem.2013.12.005. View

Myhrstad M, Carlsen H, Nordstrom O, Blomhoff R, Moskaug J . Flavonoids increase the intracellular glutathione level by transactivation of the gamma-glutamylcysteine synthetase catalytical subunit promoter. Free Radic Biol Med. 2002; 32(5):386-93. DOI: 10.1016/s0891-5849(01)00812-7. View

10.

Hossain M, Choi H, Hwang J, Abdal Dayem A, Kim J, Kim Y . Antiviral activity of 3,4'-dihydroxyflavone on influenza a virus. J Microbiol. 2014; 52(6):521-6. DOI: 10.1007/s12275-014-4212-z. View

11.

Davidson K, Mason E, Pera M . The pluripotent state in mouse and human. Development. 2015; 142(18):3090-9. DOI: 10.1242/dev.116061. View

12.

Lee E, Kang Y, Kim J, Lee H, Cho S . Modulation of apoptosis in HaCaT keratinocytes via differential regulation of ERK signaling pathway by flavonoids. J Biol Chem. 2005; 280(36):31498-507. DOI: 10.1074/jbc.M505537200. View

13.

Abarikwu S, Olufemi P, Lawrence C, Wekere F, Ochulor A, Barikuma A . Rutin, an antioxidant flavonoid, induces glutathione and glutathione peroxidase activities to protect against ethanol effects in cadmium-induced oxidative stress in the testis of adult rats. Andrologia. 2016; 49(7). DOI: 10.1111/and.12696. View

14.

Trapnell C, Hendrickson D, Sauvageau M, Goff L, Rinn J, Pachter L . Differential analysis of gene regulation at transcript resolution with RNA-seq. Nat Biotechnol. 2012; 31(1):46-53. PMC: 3869392. DOI: 10.1038/nbt.2450. View

15.

Kim Y, Rim Y, Yi H, Park N, Park S, Ju J . The Generation of Human Induced Pluripotent Stem Cells from Blood Cells: An Efficient Protocol Using Serial Plating of Reprogrammed Cells by Centrifugation. Stem Cells Int. 2016; 2016:1329459. PMC: 4989082. DOI: 10.1155/2016/1329459. View

16.

Vivier E, Raulet D, Moretta A, Caligiuri M, Zitvogel L, Lanier L . Innate or adaptive immunity? The example of natural killer cells. Science. 2011; 331(6013):44-9. PMC: 3089969. DOI: 10.1126/science.1198687. View

17.

Chen K, Ge B, Ma H, Liu X, Bai M, Wang Y . Icariin, a flavonoid from the herb Epimedium enhances the osteogenic differentiation of rat primary bone marrow stromal cells. Pharmazie. 2006; 60(12):939-42. View

18.

Trapnell C, Williams B, Pertea G, Mortazavi A, Kwan G, van Baren M . Transcript assembly and quantification by RNA-Seq reveals unannotated transcripts and isoform switching during cell differentiation. Nat Biotechnol. 2010; 28(5):511-5. PMC: 3146043. DOI: 10.1038/nbt.1621. View

19.

Hossain M, Abdal Dayem A, Han J, Yin Y, Kim K, Saha S . Molecular Mechanisms of the Anti-Obesity and Anti-Diabetic Properties of Flavonoids. Int J Mol Sci. 2016; 17(4):569. PMC: 4849025. DOI: 10.3390/ijms17040569. View

20.

Nichols J, Smith A . Naive and primed pluripotent states. Cell Stem Cell. 2009; 4(6):487-92. DOI: 10.1016/j.stem.2009.05.015. View