Nipped-A regulates intestinal stem cell proliferation in Drosophila

Development. 2017 Feb 15;144(4):612-623. doi: 10.1242/dev.142703.

Abstract

Adult stem cells uphold a delicate balance between quiescent and active states, a deregulation of which can lead to age-associated diseases such as cancer. In Drosophila, intestinal stem cell (ISC) proliferation is tightly regulated and mis-regulation is detrimental to intestinal homeostasis. Various factors are known to govern ISC behavior; however, transcriptional changes in ISCs during aging are still unclear. RNA sequencing of young and old ISCs newly identified Nipped-A, a subunit of histone acetyltransferase complexes, as a regulator of ISC proliferation that is upregulated in old ISCs. We show that Nipped-A is required for maintaining the proliferative capacity of ISCs during aging and in response to tissue-damaging or tumorigenic stimuli. Interestingly, Drosophila Myc cannot compensate for the effect of the loss of Nipped-A on ISC proliferation. Nipped-A seems to be a superordinate regulator of ISC proliferation, possibly by coordinating different processes including modifying the chromatin landscape of ISCs and progenitors.

Keywords: Aging; Chromatin; Intestine; Myc; Stem cell; TRRAP.

MeSH terms

  • Adult Stem Cells / cytology*
  • Aging
  • Animals
  • Cell Cycle
  • Cell Differentiation
  • Cell Proliferation
  • Cell Separation
  • Chromatin / metabolism
  • Drosophila Proteins / physiology*
  • Drosophila melanogaster / physiology*
  • Flow Cytometry
  • Gene Expression Regulation, Developmental*
  • Green Fluorescent Proteins / metabolism
  • Histones / metabolism
  • Homeostasis
  • Intestines / cytology*
  • Phenotype
  • Proto-Oncogene Proteins c-myc / metabolism
  • RNA Interference
  • Sequence Analysis, RNA
  • Signal Transduction
  • Transcription Factors / physiology*

Substances

  • Chromatin
  • Drosophila Proteins
  • Histones
  • NIPPED-A protein, Drosophila
  • Proto-Oncogene Proteins c-myc
  • Transcription Factors
  • Green Fluorescent Proteins