The self-renewing ability of a stem cell is controlled by its specialized micro-environment or niche, whereas epigenetic regulation of gene expression by chromatin remodeling factors underlies cell fate determination. Here we report that the adenosine triphosphate–dependent chromatin remodeling factors ISWI and DOM control germline stem cell and somatic stem cell self-renewal in the Drosophila ovary, respectively. The iswi mutant germline stem cells are lost rapidly because of defects in responding to bone morphogenetic protein niche signals and in repressing differentiation, whereas the dom mutant somatic stem cells are lost because of defective self-renewal. This work demonstrates that different stem cell types can use different chromatin remodeling factors to control cell self-renewal.