Super-Enhancers in Placental Development and Diseases

TL;DR

This paper reviews how super-enhancers regulate placental development and diseases by controlling gene networks in trophoblast cells.

Contribution

The paper highlights recent advances in understanding super-enhancers' roles in placental development and disease pathophysiology.

Findings

Super-enhancers regulate trophoblast cell proliferation and differentiation through complex gene networks.

SEs are associated with master regulator genes and influence tissue-specific stem cell functions.

SEs contribute to placental dysfunctions and may offer therapeutic insights for related diseases.

Abstract

The proliferation of trophoblast stem (TS) cells and their differentiation into multiple lineages are pivotal for placental development and functions. Various transcription factors (TFs), such as CDX2, EOMES, GATA3, TFAP2C, and TEAD4, along with their binding sites and cis-regulatory elements, have been studied for their roles in trophoblast cells. While previous studies have primarily focused on individual enhancer regions in trophoblast development and differentiation, recent attention has shifted towards investigating the role of super-enhancers (SEs) in different trophoblast cell lineages. SEs are clusters of regulatory elements enriched with transcriptional regulators, forming complex gene regulatory networks via differential binding patterns and the synchronized stimulation of multiple target genes. Although the exact role of SEs remains unclear, they are commonly found near master regulator genes for specific cell types and are implicated in the transcriptional regulation of tissue-specific stem cells and lineage determination. Additionally, super-enhancers play a crucial role in regulating cellular growth and differentiation in both normal development and disease pathologies. This review summarizes recent advances on SEs’ role in placental development and the pathophysiology of placental diseases, emphasizing the potential for identifying SE-driven networks in the placenta to provide valuable insights for developing therapeutic strategies to address placental dysfunctions.

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