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Super-enhancer-guided mapping of regulatory networks controlling mouse trophoblast stem cells

Author

Listed:
  • Bum-Kyu Lee

    (The University of Texas at Austin
    The University of Texas at Austin)

  • Yu jin Jang

    (The University of Texas at Austin)

  • Mijeong Kim

    (The University of Texas at Austin)

  • Lucy LeBlanc

    (The University of Texas at Austin
    The University of Texas at Austin)

  • Catherine Rhee

    (The University of Texas at Austin)

  • Jiwoon Lee

    (The University of Texas at Austin)

  • Samuel Beck

    (The University of Texas at Austin)

  • Wenwen Shen

    (The University of Texas at Austin)

  • Jonghwan Kim

    (The University of Texas at Austin
    The University of Texas at Austin
    The University of Texas at Austin)

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.

Suggested Citation

  • Bum-Kyu Lee & Yu jin Jang & Mijeong Kim & Lucy LeBlanc & Catherine Rhee & Jiwoon Lee & Samuel Beck & Wenwen Shen & Jonghwan Kim, 2019. "Super-enhancer-guided mapping of regulatory networks controlling mouse trophoblast stem cells," Nature Communications, Nature, vol. 10(1), pages 1-11, December.
    • Handle: RePEc:nat:natcom:v:10:y:2019:i:1:d:10.1038_s41467-019-12720-6
    DOI: 10.1038/s41467-019-12720-6
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    Cited by:

    1. Mohammad Jaber & Ahmed Radwan & Netanel Loyfer & Mufeed Abdeen & Shulamit Sebban & Areej Khatib & Hazar Yassen & Thorsten Kolb & Marc Zapatka & Kirill Makedonski & Aurelie Ernst & Tommy Kaplan & Yosef, 2022. "Comparative parallel multi-omics analysis during the induction of pluripotent and trophectoderm states," Nature Communications, Nature, vol. 13(1), pages 1-21, December.
    2. Andreas Lackner & Michael Müller & Magdalena Gamperl & Delyana Stoeva & Olivia Langmann & Henrieta Papuchova & Elisabeth Roitinger & Gerhard Dürnberger & Richard Imre & Karl Mechtler & Paulina A. Lato, 2023. "The Fgf/Erf/NCoR1/2 repressive axis controls trophoblast cell fate," Nature Communications, Nature, vol. 14(1), pages 1-20, December.
    3. Kaela M. Varberg & Esteban M. Dominguez & Boryana Koseva & Joseph M. Varberg & Ross P. McNally & Ayelen Moreno-Irusta & Emily R. Wesley & Khursheed Iqbal & Warren A. Cheung & Carl Schwendinger-Schreck, 2023. "Extravillous trophoblast cell lineage development is associated with active remodeling of the chromatin landscape," Nature Communications, Nature, vol. 14(1), pages 1-23, December.

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