Transcriptional Bursting in Pluripotent Stem Cells

Transcriptional bursting, the stochastic production of mRNA in episodic pulses, is a fundamental source of cell-to-cell heterogeneity. In pluripotent stem cells (PSCs), these bursting dynamics at core pluripotency loci are not just noise but critical determinants of identity maintenance and lineage commitment. This review synthesizes current quantitative frameworks for dissecting bursting kinetics and elaborates on the multilayered regulatory hierarchy that governs them, ranging from promoter-intrinsic features and 3D genome architecture to the formation of transcriptional condensates via liquid-liquid phase separation (LLPS). By integrating findings from genomic profiling and live-cell imaging, we highlight how the integrated action between super-enhancers and epigenetic states shapes the unique bursting dynamics in PSCs. Furthermore, we explore the functional consequences of these kinetics in pluripotency surveillance and cell fate decisions. Collectively, this review establishes a unified regulatory framework, providing novel insights for understanding stem cell heterogeneity and offering key insights for regenerative medicine.