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ZBTB12 is a molecular barrier to dedifferentiation in human pluripotent stem cells

Author

Listed:
  • Dasol Han

    (University of California)

  • Guojing Liu

    (University of California
    Novogene Co., Ltd)

  • Yujeong Oh

    (Pohang University of Science and Technology (POSTECH))

  • Seyoun Oh

    (Pohang University of Science and Technology (POSTECH))

  • Seungbok Yang

    (Pohang University of Science and Technology (POSTECH))

  • Lori Mandjikian

    (University of California)

  • Neha Rani

    (University of California
    Indian Institute of Technology)

  • Maria C. Almeida

    (University of California
    Center for Natural and Human Sciences São Bernardo do Campo)

  • Kenneth S. Kosik

    (University of California)

  • Jiwon Jang

    (Pohang University of Science and Technology (POSTECH))

Abstract

Development is generally viewed as one-way traffic of cell state transition from primitive to developmentally advanced states. However, molecular mechanisms that ensure the unidirectional transition of cell fates remain largely unknown. Through exact transcription start site mapping, we report an evolutionarily conserved BTB domain-containing zinc finger protein, ZBTB12, as a molecular barrier for dedifferentiation of human pluripotent stem cells (hPSCs). Single-cell RNA sequencing reveals that ZBTB12 is essential for three germ layer differentiation by blocking hPSC dedifferentiation. Mechanistically, ZBTB12 fine-tunes the expression of human endogenous retrovirus H (HERVH), a primate-specific retrotransposon, and targets specific transcripts that utilize HERVH as a regulatory element. In particular, the downregulation of HERVH-overlapping long non-coding RNAs (lncRNAs) by ZBTB12 is necessary for a successful exit from a pluripotent state and lineage derivation. Overall, we identify ZBTB12 as a molecular barrier that safeguards the unidirectional transition of metastable stem cell fates toward developmentally advanced states.

Suggested Citation

  • Dasol Han & Guojing Liu & Yujeong Oh & Seyoun Oh & Seungbok Yang & Lori Mandjikian & Neha Rani & Maria C. Almeida & Kenneth S. Kosik & Jiwon Jang, 2023. "ZBTB12 is a molecular barrier to dedifferentiation in human pluripotent stem cells," Nature Communications, Nature, vol. 14(1), pages 1-16, December.
    • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-36178-9
    DOI: 10.1038/s41467-023-36178-9
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    as
    1. Edward J. Grow & Ryan A. Flynn & Shawn L. Chavez & Nicholas L. Bayless & Mark Wossidlo & Daniel J. Wesche & Lance Martin & Carol B. Ware & Catherine A. Blish & Howard Y. Chang & Renee A. Reijo Pera & , 2015. "Intrinsic retroviral reactivation in human preimplantation embryos and pluripotent cells," Nature, Nature, vol. 522(7555), pages 221-225, June.
    2. Hitoshi Niwa & Kazuya Ogawa & Daisuke Shimosato & Kenjiro Adachi, 2009. "A parallel circuit of LIF signalling pathways maintains pluripotency of mouse ES cells," Nature, Nature, vol. 460(7251), pages 118-122, July.
    3. David R. Bentley & Shankar Balasubramanian & Harold P. Swerdlow & Geoffrey P. Smith & John Milton & Clive G. Brown & Kevin P. Hall & Dirk J. Evers & Colin L. Barnes & Helen R. Bignell & Jonathan M. Bo, 2008. "Accurate whole human genome sequencing using reversible terminator chemistry," Nature, Nature, vol. 456(7218), pages 53-59, November.
    4. Sean C. Bendall & Morag H. Stewart & Pablo Menendez & Dustin George & Kausalia Vijayaragavan & Tamra Werbowetski-Ogilvie & Veronica Ramos-Mejia & Anne Rouleau & Jiabi Yang & Marc Bossé & Gilles Lajoie, 2007. "IGF and FGF cooperatively establish the regulatory stem cell niche of pluripotent human cells in vitro," Nature, Nature, vol. 448(7157), pages 1015-1021, August.
    5. Qi-Long Ying & Jason Wray & Jennifer Nichols & Laura Batlle-Morera & Bradley Doble & James Woodgett & Philip Cohen & Austin Smith, 2008. "The ground state of embryonic stem cell self-renewal," Nature, Nature, vol. 453(7194), pages 519-523, May.
    6. Xiaodong Liu & John F. Ouyang & Fernando J. Rossello & Jia Ping Tan & Kathryn C. Davidson & Daniela S. Valdes & Jan Schröder & Yu B. Y. Sun & Joseph Chen & Anja S. Knaupp & Guizhi Sun & Hun S. Chy & Z, 2020. "Reprogramming roadmap reveals route to human induced trophoblast stem cells," Nature, Nature, vol. 586(7827), pages 101-107, October.
    7. Jiadong Liu & Mingwei Gao & Jiangping He & Kaixin Wu & Siyuan Lin & Lingmei Jin & Yaping Chen & He Liu & Junjie Shi & Xiwei Wang & Lei Chang & Yingying Lin & Yu-Li Zhao & Xiaofei Zhang & Man Zhang & G, 2021. "The RNA m6A reader YTHDC1 silences retrotransposons and guards ES cell identity," Nature, Nature, vol. 591(7849), pages 322-326, March.
    8. Yingyao Zhou & Bin Zhou & Lars Pache & Max Chang & Alireza Hadj Khodabakhshi & Olga Tanaseichuk & Christopher Benner & Sumit K. Chanda, 2019. "Metascape provides a biologist-oriented resource for the analysis of systems-level datasets," Nature Communications, Nature, vol. 10(1), pages 1-10, December.
    9. Jing Zhang & Donghoon Lee & Vineet Dhiman & Peng Jiang & Jie Xu & Patrick McGillivray & Hongbo Yang & Jason Liu & William Meyerson & Declan Clarke & Mengting Gu & Shantao Li & Shaoke Lou & Jinrui Xu &, 2020. "An integrative ENCODE resource for cancer genomics," Nature Communications, Nature, vol. 11(1), pages 1-11, December.
    Full references (including those not matched with items on IDEAS)

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