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.