Chromatin is organized as chromosome territories in the nucleus of an interphase cell. The cell-type- and cell-state-specific organization of chromatin including the location, volume, compaction level, and spatial arrangement of chromosome territories are the major determinants of genome function. In addition, in response to different signaling stimuli and regulatory cues, it is the dynamic adaptation of chromatin structure that establishes and organizes transcriptional programs. It is known that varying levels of stemness are defined by gene regulatory networks. Accordingly, chromatin is the main milieu to host the transcriptional programs and gene regulatory networks responsible for the stemness status of a cell. In this review, our current understanding of the spatial organization of chromatin and the ways by which it defines stemness are discussed. In particular, the role of lncRNAs that regulate and affect chromatin organization and stemness properties are delineated. These roles can be categorized into the topics of specific binding to and epigenetic regulation of the promoter of pluripotency genes, their interaction with transcription factors, coordinating the intra- and inter-chromosomal looping of pluripotency-related genes, and their RNA-independent functions. This review brings together the results of studies that have begun to clarify the emerging roles of lncRNAs in the regulation of chromatin organization adapted for stemness and cancer plasticity.

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