IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v11y2020i1d10.1038_s41467-020-14737-8.html
   My bibliography  Save this article

Klf5 acetylation regulates luminal differentiation of basal progenitors in prostate development and regeneration

Author

Listed:
  • Baotong Zhang

    (Emory University
    Emory University School of Medicine)

  • Xinpei Ci

    (Emory University
    Emory University School of Medicine
    University of British Columbia)

  • Ran Tao

    (Emory University
    Emory University School of Medicine
    Central South University)

  • Jianping Jenny Ni

    (Emory University
    Emory University School of Medicine)

  • Xiaoyan Xuan

    (Emory University
    University of Virginia Health System
    Zhengzhou University)

  • Jamie L. King

    (Emory University
    Emory University School of Medicine)

  • Siyuan Xia

    (Emory University
    Emory University School of Medicine)

  • Yixiang Li

    (Emory University
    Emory University School of Medicine)

  • Henry F. Frierson

    (University of Virginia Health System)

  • Dong-Kee Lee

    (Baylor College of Medicine)

  • Jianming Xu

    (Baylor College of Medicine)

  • Adeboye O. Osunkoya

    (Emory University
    Emory University School of Medicine
    Emory University School of Medicine)

  • Jin-Tang Dong

    (Emory University
    Emory University School of Medicine)

Abstract

Prostate development depends on balanced cell proliferation and differentiation, and acetylated KLF5 is known to alter epithelial proliferation. It remains elusive whether post-translational modifications of transcription factors can differentially determine adult stem/progenitor cell fate. Here we report that, in human and mouse prostates, Klf5 is expressed in both basal and luminal cells, with basal cells preferentially expressing acetylated Klf5. Functionally, Klf5 is indispensable for maintaining basal progenitors, their luminal differentiation, and the proliferation of their basal and luminal progenies. Acetylated Klf5 is also essential for basal progenitors’ maintenance and proper luminal differentiation, as deacetylation of Klf5 causes excess basal-to-luminal differentiation; attenuates androgen-mediated organoid organization; and retards postnatal prostate development. In basal progenitor-derived luminal cells, Klf5 deacetylation increases their proliferation and attenuates their survival and regeneration following castration and subsequent androgen restoration. Mechanistically, Klf5 deacetylation activates Notch signaling. Klf5 and its acetylation thus contribute to postnatal prostate development and regeneration by controlling basal progenitor cell fate.

Suggested Citation

  • Baotong Zhang & Xinpei Ci & Ran Tao & Jianping Jenny Ni & Xiaoyan Xuan & Jamie L. King & Siyuan Xia & Yixiang Li & Henry F. Frierson & Dong-Kee Lee & Jianming Xu & Adeboye O. Osunkoya & Jin-Tang Dong, 2020. "Klf5 acetylation regulates luminal differentiation of basal progenitors in prostate development and regeneration," Nature Communications, Nature, vol. 11(1), pages 1-16, December.
    • Handle: RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-020-14737-8
    DOI: 10.1038/s41467-020-14737-8
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-020-14737-8
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-020-14737-8?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
    ---><---

    Citations

    Citations are extracted by the CitEc Project, subscribe to its RSS feed for this item.
    as


    Cited by:

    1. Meixia Che & Aashi Chaturvedi & Sarah A. Munro & Samuel P. Pitzen & Alex Ling & Weijie Zhang & Josh Mentzer & Sheng-Yu Ku & Loredana Puca & Yanyun Zhu & Andries M. Bergman & Tesa M. Severson & Colleen, 2021. "Opposing transcriptional programs of KLF5 and AR emerge during therapy for advanced prostate cancer," 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:11:y:2020:i:1:d:10.1038_s41467-020-14737-8. 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.

    We have no bibliographic references for this item. You can help adding them by using 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.