The Plath lab focuses on the epigenetic mechanisms that maintain pluripotency and on the epigenetic changes that are underlying differentiation and reprogramming processes. Within this context, we are studying three fundamental problems: (i) How do long-noncoding (lnc) RNAs regulate chromatin changes occurring during differentiation and reprogramming? This aspect of our work particularly centers on understanding how the X-inactivation process is regulated by the lncRNAs Xist and Tsix, how the heterochromatin of the inactive X chromosome is reset during reprogramming to pluripotency, and how the X-inactivation process differs between mouse and human development. (ii) We are dissecting the mechanisms underlying transcription factor-induced reprogramming of somatic cells to pluripotency, which helps us to understand how transcription factors drive cell fate changes and induce new chromatin and gene expression states. (iii) We are examining how the three-dimensional organization of the genome changes during differentiation and reprogramming processes, how transcriptional networks and lncRNAs regulate 3D genome organization, and how 3D genome organization in turn influences gene expression, chromatin states, and lncRNA function.