IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v13y2022i1d10.1038_s41467-022-32295-z.html
   My bibliography  Save this article

PCGF6 controls neuroectoderm specification of human pluripotent stem cells by activating SOX2 expression

Author

Listed:
  • Xianchun Lan

    (Wuhan University)

  • Song Ding

    (Wuhan University)

  • Tianzhe Zhang

    (Wuhan University)

  • Ying Yi

    (Wuhan University)

  • Conghui Li

    (Wuhan University)

  • Wenwen Jin

    (Wuhan University)

  • Jian Chen

    (Chinese Academy of Medical Sciences)

  • Kaiwei Liang

    (Wuhan University)

  • Hengbin Wang

    (Virginia Commonwealth University)

  • Wei Jiang

    (Wuhan University
    Human Genetics Resource Preservation Center of Wuhan University
    Hubei Provincial Key Laboratory of Developmentally Originated Disease)

Abstract

Polycomb group (PcG) proteins are known to repress developmental genes during embryonic development and tissue homeostasis. Here, we report that PCGF6 controls neuroectoderm specification of human pluripotent stem cells (PSCs) by activating SOX2 gene. Human PSCs with PCGF6 depletion display impaired neuroectoderm differentiation coupled with increased mesendoderm outcomes. Transcriptome analysis reveals that de-repression of the WNT/β-catenin signaling pathway is responsible for the differentiation of PSC toward the mesendodermal lineage. Interestingly, PCGF6 and MYC directly interact and co-occupy a distal regulatory element of SOX2 to activate SOX2 expression, which likely accounts for the regulation in neuroectoderm differentiation. Supporting this notion, genomic deletion of the SOX2-regulatory element phenocopies the impaired neuroectoderm differentiation, while overexpressing SOX2 rescues the neuroectoderm phenotype caused by PCGF6-depletion. Together, our study reveals that PCGF6 can function as lineage switcher between mesendoderm and neuroectoderm in human PSCs by both suppression and activation mechanisms.

Suggested Citation

  • Xianchun Lan & Song Ding & Tianzhe Zhang & Ying Yi & Conghui Li & Wenwen Jin & Jian Chen & Kaiwei Liang & Hengbin Wang & Wei Jiang, 2022. "PCGF6 controls neuroectoderm specification of human pluripotent stem cells by activating SOX2 expression," Nature Communications, Nature, vol. 13(1), pages 1-15, December.
    • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-32295-z
    DOI: 10.1038/s41467-022-32295-z
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-022-32295-z
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-022-32295-z?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    References listed on IDEAS

    as
    1. Li Chen & Qiaoqiao Tong & Xiaowen Chen & Penglei Jiang & Hua Yu & Qianbing Zhao & Lingang Sun & Chao Liu & Bin Gu & Yuping Zheng & Lijiang Fei & Xiao Jiang & Wenjuan Li & Giacomo Volpe & Mazid MD. Abd, 2021. "PHC1 maintains pluripotency by organizing genome-wide chromatin interactions of the Nanog locus," Nature Communications, Nature, vol. 12(1), pages 1-13, December.
    2. Zhonghua Gao & Pedro Lee & James M. Stafford & Melanie von Schimmelmann & Anne Schaefer & Danny Reinberg, 2014. "An AUTS2–Polycomb complex activates gene expression in the CNS," Nature, Nature, vol. 516(7531), pages 349-354, December.
    3. Thomas Dahlet & Matthias Truss & Ute Frede & Hala Al Adhami & Anaïs F. Bardet & Michael Dumas & Judith Vallet & Johana Chicher & Philippe Hammann & Sarah Kottnik & Peter Hansen & Uschi Luz & Gonzalo A, 2021. "E2F6 initiates stable epigenetic silencing of germline genes during embryonic development," Nature Communications, Nature, vol. 12(1), pages 1-14, December.
    4. Mingze Yao & Xueke Zhou & Jiajian Zhou & Shixin Gong & Gongcheng Hu & Jiao Li & Kaimeng Huang & Ping Lai & Guang Shi & Andrew P. Hutchins & Hao Sun & Huating Wang & Hongjie Yao, 2018. "PCGF5 is required for neural differentiation of embryonic stem cells," Nature Communications, Nature, vol. 9(1), pages 1-12, December.
    5. Yongli Shan & Zechuan Liang & Qi Xing & Tian Zhang & Bo Wang & Shulan Tian & Wenhao Huang & Yanqi Zhang & Jiao Yao & Yanling Zhu & Ke Huang & Yujian Liu & Xiaoshan Wang & Qianyu Chen & Jian Zhang & Bi, 2017. "PRC2 specifies ectoderm lineages and maintains pluripotency in primed but not naïve ESCs," Nature Communications, Nature, vol. 8(1), pages 1-14, December.
    Full references (including those not matched with items on IDEAS)

    Most related items

    These are the items that most often cite the same works as this one and are cited by the same works as this one.
    1. Yanjiang Liu & Gongcheng Hu & Shengxiong Yang & Mingze Yao & Zicong Liu & Chenghong Yan & Yulin Wen & Wangfang Ping & Juehan Wang & Yawei Song & Xiaotao Dong & Guangjin Pan & Hongjie Yao, 2023. "Functional dissection of PRC1 subunits RYBP and YAF2 during neural differentiation of embryonic stem cells," Nature Communications, Nature, vol. 14(1), pages 1-14, December.
    2. Takeo Kubota & Kazuki Mochizuki, 2016. "Epigenetic Effect of Environmental Factors on Autism Spectrum Disorders," IJERPH, MDPI, vol. 13(5), pages 1-12, May.
    3. Benjamin A. Nacev & Yakshi Dabas & Matthew R. Paul & Christian Pacheco & Michelle Mitchener & Yekaterina Perez & Yan Fang & Alexey A. Soshnev & Douglas Barrows & Thomas Carroll & Nicholas D. Socci & S, 2024. "Cancer-associated Histone H3 N-terminal arginine mutations disrupt PRC2 activity and impair differentiation," Nature Communications, Nature, vol. 15(1), pages 1-17, December.
    4. Beatriz del Blanco & Sergio Niñerola & Ana M. Martín-González & Juan Paraíso-Luna & Minji Kim & Rafael Muñoz-Viana & Carina Racovac & Jose V. Sanchez-Mut & Yijun Ruan & Ángel Barco, 2024. "Kdm1a safeguards the topological boundaries of PRC2-repressed genes and prevents aging-related euchromatinization in neurons," Nature Communications, Nature, vol. 15(1), pages 1-20, December.
    5. Lihu Gong & Xiuli Liu & Lianying Jiao & Xin Yang & Andrew Lemoff & Xin Liu, 2022. "CK2-mediated phosphorylation of SUZ12 promotes PRC2 function by stabilizing enzyme active site," Nature Communications, Nature, vol. 13(1), pages 1-15, December.
    6. Kentaro Mochizuki & Jafar Sharif & Kenjiro Shirane & Kousuke Uranishi & Aaron B. Bogutz & Sanne M. Janssen & Ayumu Suzuki & Akihiko Okuda & Haruhiko Koseki & Matthew C. Lorincz, 2021. "Repression of germline genes by PRC1.6 and SETDB1 in the early embryo precedes DNA methylation-mediated silencing," Nature Communications, Nature, vol. 12(1), pages 1-15, December.

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-32295-z. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    If CitEc recognized a bibliographic reference but did not link an item in RePEc to it, you can help with this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.