한빛사논문
- 조회1,833
Bum-Kyu Lee1,2, Yu jin Jang1, Mijeong Kim1, Lucy LeBlanc1,2, Catherine Rhee1, Jiwoon Lee1, Samuel Beck1, Wenwen Shen1 & Jonghwan Kim1,2,3*
1 Department of Molecular Biosciences, The University of Texas at Austin, Austin, TX 78712, USA.
2 Institute for Cellular and Molecular Biology, The University of Texas at Austin, Austin, TX 78712, USA.
3 Center for Systems and Synthetic Biology, The University of Texas at Austin, Austin, TX 78712, USA.
*Correspondence to Jonghwan Kim
Abstract
Trophectoderm (TE) lineage development is pivotal for proper implantation, placentation, and healthy pregnancy. However, only a few TE-specific transcription factors (TFs) have been systematically characterized, hindering our understanding of the process. To elucidate regulatory mechanisms underlying TE development, here we map super-enhancers (SEs) in trophoblast stem cells (TSCs) as a model. We find both prominent TE-specific master TFs (Cdx2, Gata3, and Tead4), and >150 TFs that had not been previously implicated in TE lineage, that are SE-associated. Mapping targets of 27 SE-predicted TFs reveals 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 a subset of TFs results in dysregulation of the markers for specialized cell types in placenta, suggesting a role during TE differentiation. Collectively, we characterize an expanded TE-specific regulatory network, providing a framework for understanding TE lineage development and placentation.
논문정보
- Research article
- 2019년 10월 (BRIC 등록일 2019-10-24)
- 국외 연구진
- 생명과학 > 유전자발현
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