Disclosed are the FRIL family of progenitor cell preservation factors and nucleic acids encoding the same. FRIL family members preserve progenitor cells both in vivo and ex vivo. FRIL family members find use as therapeutics for alleviating and/or reducing the hematopoietic progenitor cell-depleting activity of many cancer therapeutics. FRIL family members are also useful for isolating rare, primitive progenitor cells.