Figure 1.

LSD1 inhibition promotes expansion of human HSPCs in vitro. (A) Dose-titration experiment showing the effect of 3 LSD1 inhibitors (2-PCPA, GSK-LSD1, or RN-1) on UCB-derived CD34⁺ HSPC expansion rate compared with the starting cell number (data from 2 repeats). (B) Total numbers of CD34⁺ cells obtained after treating 10 000 fresh CD34⁺ cells with 2-PCPA, GSK-LSD1, or RN-1 at their respective half-maximal inhibitory concentration (IC50)/16 concentration (2-PCPA-1.25 μM; GSK_LSD1-1 nM, RN1-4.37 nM) for 6 days. (C) FACS plots showing the frequency (C) and graph showing the total numbers (D) of CD34⁺EPCR⁺ cells obtained after treating 10 000 fresh CD34⁺ cells with 2-PCPA, GSK-LSD1 or RN-1, at their respective IC50/16 concentration, for 6 days. Data from 3 replicates from 1 of 5 independent experiments with similar results are shown. Frequency (E) and numbers (F) of CD34⁺EPCR⁺ cells obtained after treating UCB CD34⁺CD38⁻CD45RA⁻CD90⁺ cells with 2-PCPA for 6 days. (G) Total numbers of CD34⁺EPCR⁺ cells obtained after treating BM-derived CD34⁺CD38⁻CD45RA⁻CD90⁺ cells with 2-PCPA for 6 days. Data from 3 replicates from 1 of 2 independent experiments with similar results. *P ≤ .05, **P ≤ .01, ***P ≤ .001, ****P ≤ .0001. ns, not significant.