Regulation of X-linked gene dose between females(XX) and males(XY) is critically necessary to prevent disease associated over-expression in females. X-linked equilibrium is achieved by X-Chromosome Inactivation (XCI), initiated by Xist RNA to inactivate one allele (Xi). Silencing of the Xi is maintained across all cell divisions by retention of Xist RNA transcripts and maintenance of a condensed, bipartite allele. However, our lab made a seminal discovery that naïve, quiescent B lymphocytes express Xist, but lack Xist RNA at the Xi. Upon lymphocyte activation, Xist RNA dynamically re-localizes to the Xi. Lymphocytes are the first cell type to display dynamic XCI, thus how differential localization of Xist RNA impacts Xi silencing and regulation of Xi-specific structure is unknown. Further, this finding implores us to ask whether other cell types, particularly quiescent cells, could show unique XCI regulation. Here, I utilize various primary cells to ask whether XCI maintenance has cell-type specific regulatory mechanisms outside of lymphocytes, and how varied Xist RNA localization could influence XCI maintenance. Examination of Xist RNA localization across adult stem cells determined that dispersed Xist RNA is not directly linked to quiescence. Further, we identify a new cell type, satellite cells, with dynamic XCI maintenance upon activation. In AT2 stem cells of the lung, we observe loss of localized Xist RNA coupled with a significant number of XCI escape genes. The results from these studies suggest that varied XCI maintenance is a more widespread, cell-type specific phenomenon with implications for sex-differences in stem cell function. Finally, upon B lymphocyte activation, the Xi displays TAD-like structures with increased interactions that appear independent from escape gene expression. Xist RNA re-localizes to the Xi in parallel to activation induced Xi remodeling, thus we hypothesized that Xist RNA maintains Xi structure in stimulated B cells. Remarkably, we find that Xist RNA is required to prevent extensive activation-induced Xi remodeling, but surprisingly also prevents modulation to Xi structure in naïve B cells. Together, this work challenges the paradigms of XCI maintenance and lays the foundation for further work in which to understand the connections between varied XCI maintenance and sex-biased cellular functions.