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

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 and Jin-Tang Dong ()
Additional contact information
Baotong Zhang: Emory University
Xinpei Ci: Emory University
Ran Tao: Emory University
Jianping Jenny Ni: Emory University
Xiaoyan Xuan: Emory University
Jamie L. King: Emory University
Siyuan Xia: Emory University
Yixiang Li: Emory University
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
Jin-Tang Dong: Emory University

Nature Communications, 2020, vol. 11, issue 1, 1-16

Abstract: 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.

Date: 2020
References: Add references at CitEc
Citations: View citations in EconPapers (1)

Downloads: (external link)
https://www.nature.com/articles/s41467-020-14737-8 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-020-14737-8

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-020-14737-8

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().