SWI/SNF Chromatin Remodeling in Multipotency

Virginia Commonwealth University, Richmond VA

Investigators

Abstract

Stem cells have the potential to generate a variety of different cell types and are important for the renewal of cells in adulthood, while differentiated cells are committed to perform a specific function. In recent years, researchers have found that differentiated cells can be converted into stem cells by introducing a few key genetic factors into the differentiated cell. In order to harness this potential for regenerative medicine, it is important to understand the genetic factors that give stem cells their unique potential. The genetic model organism Caenorhabditis elegans has many advantages for studying this process. Importantly, the fates of all cells in the animal are known. This research focuses on two cells that arise through a single cell division and have very different potential: one is capable of making all support cells of the reproductive system, while the other is differentiated. The genetic factors that are different between these two cells will be identified and this will provide insight into what makes a stem cell different from a differentiated cell. In order to train the next generation of STEM professionals, this research will be incorporated into an advanced undergraduate laboratory that gives students a genuine research experience. Students are expected to be from diverse backgrounds, including racial and ethnic groups that are traditionally underrepresented in STEM fields. Adult stem and progenitor cells are capable of producing a few related cell types. The genes and molecular mechanisms that regulate and determine this capacity are not well understood. This proposal uses progenitors of the C. elegans reproductive system as a model for defining the genetic determinants of multipotency. The somatic gonadal progenitors (SGPs) are multipotent progenitors that generate all somatic tissues of the reproductive system. Each SGP is the product of a cell division that produces one SGP and one differentiated cell, the head mesodermal cell (hmc). Therefore, in this single cell division the potential to generate all of the somatic gonadal types is differentially segregated into one daughter cell. SWI/SNF chromatin remodeling complexes are highly conserved, large protein complexes that regulate chromatin structure and result in gene activation or repression. Molecularly distinct SWI/SNF complexes are expressed in pluripotent stem cells, multipotent progenitors, and differentiated cells, suggesting that different SWI/SNF complexes are likely to play important roles in each of these different cell states. Components of the C. elegans SWI/SNF complex are required to distinguish SGPs from their differentiated hmc sisters. The goals of this proposal are to identify the genes that distinguish multipotent SGPs from their differentiated hmc sisters, and to identify the mechanisms by which SWI/SNF chromatin remodeling complexes regulate these cell fates. These experiments will provide insight into the genes and molecular mechanisms that distinguish multipotent progenitors from differentiated cells, and will identify the role SWI/SNF chromatin remodeling complexes in these cell fates.