Esrrb Regulates Specific Feed-Forward Loops to Transit From Pluripotency Into Early Stages of Differentiation

• Published in: Frontiers in cell and developmental biology Vol. 10; p. 820255
• Main Authors: Mazloom, Amin R, Xu, Huilei, Reig-Palou, Jaume, Vasileva, Ana, Román, Angel-Carlos, Mulero-Navarro, Sonia, Lemischka, Ihor R, Sevilla, Ana
• Format: Journal Article
• Language: English
• Published: Switzerland Frontiers Media S.A 16.05.2022
• Subjects: Cell and Developmental Biology; estrogen related receptor beta; feed-forward loops; MicroRNAs; mouse embryonic stem cells; network dynamic analysis; feed-forward loops; network dynamic analysis; estrogen related receptor beta; mouse embryonic stem cells; MicroRNAs
• ISSN: 2296-634X; 2296-634X
• DOI: 10.3389/fcell.2022.820255

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 play a relevant role in cellular differentiation, the role of miRNAs integrated into gene regulatory networks and its dynamic changes during these early stages of embryonic stem cell (ESC) differentiation remain elusive. Here we describe the dynamic transcriptional regulatory circuitry of stem cells that incorporate protein-coding and miRNA genes based on miRNA 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 stem cell miRNA expression program and integrates dynamic changes of feed-forward loops contributing to the early stages of cell differentiation upon its downregulation. Together these findings provide new insights on the architecture of the combined transcriptional post-transcriptional regulatory network in embryonic stem cells.