[초청강연] Searching for master regulators: trophoblast differentiation and trans-differentiation

Abstract:
Trophectoderm (TE) lineage development is pivotal for proper implantation, placentation, and healthy pregnancy, but only a few TE-specific transcription factors (TFs) have been systematically characterized, hindering our understanding of the process. To elucidate regulatory mechanisms underlying TE lineage development, we map super-enhancers (SEs, or enhancer clusters) in trophoblast stem cells (TSCs) as a model, revealing that both prominent TE-specific master TFs (Cdx2, Gata3, and Tead4) and >150 TFs never been implicated in TE lineage are SE-associated. Mapping targets of 27 SE-predicted TFs revealed a highly intertwined transcriptional regulatory circuitry. Intriguingly, SE-predicted TFs show 4 distinct expression patterns with dynamic alterations of their targets during TSC differentiation. Furthermore, depletion of novel TFs - Meis1, Pou3f1, Maff, or Mafk - results in dysregulation of the markers for specialized cell types in placenta, suggesting their unique roles during TE differentiation. Collectively, we reveal expanded TE-specific regulatory networks, providing a framework for understanding TE lineage development and placentation.