Modulators of TRIM-NHL proteins and their use for modulating the proliferation and differentiation potential of stem cells and progenitor cells. Inhibitors of TRIM-NHL proteins, e.g. TRIM32, are useful for stem cell maintenance in vitro and in vivo . Assay methods for identifying TRIM-NHL protein modulators make use of the E3 ligase activity of TRIM32 or its interaction with Argonaute-1.