3,2′-Dihydroxyflavone Improves the Proliferation and Survival of Human Pluripotent Stem Cells and Their Differentiation into Hematopoietic Progenitor Cells
Open Access
- 2 March 2020
- journal article
- research article
- Published by MDPI AG in Journal of Clinical Medicine
- Vol. 9 (3), 669
- https://doi.org/10.3390/jcm9030669
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.Funding Information
- National Research Foundation of Korea (NRF-2019M3A9H1030682, NRF-2015R1A5A1009701)
This publication has 77 references indexed in Scilit:
- Redox homeostasis: the linchpin in stem cell self-renewal and differentiationCell Death & Disease, 2013
- Control of the Embryonic Stem Cell StateCell, 2011
- Epigenetic memory in induced pluripotent stem cellsNature, 2010
- Transcript assembly and quantification by RNA-Seq reveals unannotated transcripts and isoform switching during cell differentiationNature Biotechnology, 2010
- Oct-4 controls cell-cycle progression of embryonic stem cellsBiochemical Journal, 2010
- Naive and Primed Pluripotent StatesCell Stem Cell, 2009
- Induction of Pluripotent Stem Cells from Adult Human Fibroblasts by Defined FactorsCell, 2007
- A ROCK inhibitor permits survival of dissociated human embryonic stem cellsNature Biotechnology, 2007
- Core Transcriptional Regulatory Circuitry in Human Embryonic Stem CellsCell, 2005
- Analysis of Relative Gene Expression Data Using Real-Time Quantitative PCR and the 2−ΔΔCT MethodMethods, 2001