EED, a member of the polycomb group, is required for nephron differentiation and the maintenance of nephron progenitor cells

Le Zhang, Sandrine Ettou, Myda Khalid, Mary Taglienti, Dhawal Jain, Youngsook L. Jung, Catherine Seager, Yongqing Liu, Kar Hui Ng, Peter J. Park, Jordan A. Kreidberg*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

9 Scopus citations

Abstract

Epigenetic regulation of gene expression has a crucial role allowing for the self-renewal and differentiation of stem and progenitor populations during organogenesis. The mammalian kidney maintains a population of self-renewing stem cells that differentiate to give rise to thousands of nephrons, which are the functional units that carry out filtration to maintain physiological homeostasis. The polycomb repressive complex 2 (PRC2) epigenetically represses gene expression during development by placing the H3K27me3 mark on histone H3 at promoter and enhancer sites, resulting in gene silencing. To understand the role of PRC2 in nephron differentiation, we conditionally inactivated the Eed gene, which encodes a nonredundant component of the PRC2 complex, in nephron progenitor cells. Resultant kidneys were smaller and showed premature loss of progenitor cells. The progenitors in Eed mutant mice that were induced to differentiate did not develop into properly formed nephrons. Lhx1, normally expressed in the renal vesicle,was overexpressed in kidneys of Eedmutantmice. Thus,PRC2 has a crucial role in suppressing the expression of genes that maintain the progenitor state, allowing nephron differentiation to proceed.

Original languageEnglish (US)
Article numberdev157149
JournalDevelopment (Cambridge)
Volume145
Issue number14
DOIs
StatePublished - Jul 15 2018

Keywords

  • Epigenetics
  • Histone methylation
  • Kidney development
  • Nephron
  • Stem cell

ASJC Scopus subject areas

  • Molecular Biology
  • Developmental Biology

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