Multiple mechanisms of UM171 promote ex vivo HSC expansion. In standard human HSC culture conditions, high levels of MYC and CoREST accumulate, resulting in loss of transplantable HSCs. UM171 induces human HSC expansion ex vivo, at least in part, by degrading MYC and the LSD1/CoREST complex via its ability to recruit them to the CRL3^KBTBD4 E3 ubiquitin ligase.