LSD1 and CoREST restrict ex vivo propagation of human HSCs and are targets of UM171. (A) LSD and/or the CoREST complex inhibit ex vivo expansion of HSCs. (B) Inhibition of LSD1 (pharmacological or CRISPR/Cas9) or inhibition of the CoREST core member, RCOR1 (via CRISPR/Cas9), resulted in ex vivo expansion of HSCs. (C) UM171 treatment results in polyubiquitination and degradation of LSD1 and CoREST leading to ex vivo expansion of HSCs.