Esrrb Regulates Specific Feed-Forward Loops to Transit from Pluripotency into Early Stages of Differentiation

Characterization of pluripotent states, in which cells can both self-renew or differentiate, with the irreversible loss of pluripotency, are important research areas in developmental biology. Although microRNAs (miRNAs) have been shown to be crucial for embryonic stem (ES) self-renewal maintenance and cellular differentiation, the role of miRNAs integrated into gene regulatory networks and its dynamic changes during these state transitions remain elusive. Here we describe the dynamic transcriptional regulatory circuitry of ES cells that incorporate protein-coding and miRNA genes based on microRNA array expression and quantitative sequencing of short transcripts upon the downregulation of the Estrogen Related Receptor Beta (Esrrb). The data reveals how Esrrb, a key stem cell transcription factor, regulates a specific ES cell miRNA expression program and integrates dynamic changes of feed forward loops contributing to the exit of the pluripotency state upon its downregulation. Together these findings provide new insights on the architecture of the combined transcriptional post-transcriptional regulatory network in stem cells. Total of 12 murine embryonic stem cell line with controllable Esrrb expression (Esrrb_R) samples; Esrrb day0, Esrrb kd day1, Esrrb kd day3 and Esrrb kd Day5; all performed in triplicates Please note that the common reference pool includes samples s1 to s3; s1: Esrrb Day0 Rep1 s2: Esrrb Day0 Rep2 s3: Esrrb Day0 Rep3