Characterizing the role of SWI/SNF-related chromatin remodeling complexes in planarian regeneration and stem cell function

Abstract

SWI/SNF-related chromatin remodeling complexes, including the human BAF and PBAF complexes, are involved in controlling stem cell pluripotency and differentiation in many species. However, these complexes have not been fully characterized in planarians, an emerging model for the in vivo study of stem cells. These flatworms have the ability to regenerate following injury or amputation, and we sought to investigate the role of chromatin remodeling in this process through bioinformatic and genetic characterization of the SWI/SNF-like complexes in Schmidtea mediterranea. We identified planarian homologs of all human BAF and PBAF subunits, and then examined their expression patterns and RNAi phenotypes. We found that the genes are expressed in both stem cells and differentiated tissues, and their knockdown results in impaired regeneration and other phenotypes indicating stem cell dysfunction. Knockdown of core complex members and Smed-ARID1 led to an increase in steady-state mitotic cell number, however, the stereotypical proliferative response that follows amputation was reduced following Smed-BRG1/BRM-2 RNAi. The number of differentiating epidermal lineage cells and expression of epidermal and muscle lineage markers were also reduced following SWI/SNF knockdown. Our findings provide insight into the importance of the SWI/SNF complex in stem cell function and cellular differentiation in planarians. Keywords: Planarian, Schmidtea mediterranea, Stem cell, Regeneration, SWI/SNF, BAF