Amitosis of Polyploid Cells Regenerates Functional Stem Cells in the Drosophila Intestine

Elena M. Lucchetta, Benjamin Ohlstein

Research output: Contribution to journalArticlepeer-review

37 Scopus citations

Abstract

Organ fitness depends on appropriate maintenance of stem cell populations, and aberrations in functional stem cell numbers are associated with malignancies and aging. Symmetrical division is the best characterized mechanism of stem cell replacement, but other mechanisms could also be deployed, particularly in situations of high stress. Here, we show that after severe depletion, intestinal stem cells (ISCs) in the Drosophila midgut are replaced by spindle-independent ploidy reduction of cells in the enterocyte lineage through a process known as amitosis. Amitosis is also induced by the functional loss of ISCs coupled with tissue demand and in aging flies, underscoring the generality of this mechanism. However, we also found that random homologous chromosome segregation during ploidy reduction can expose deleterious mutations through loss of heterozygosity. Together, our results highlight amitosis as an unappreciated mechanism for restoring stem cell homeostasis, but one with some associated risk in animals carrying mutations.

Original languageEnglish (US)
Pages (from-to)609-620.e6
JournalCell Stem Cell
Volume20
Issue number5
DOIs
StatePublished - May 4 2017
Externally publishedYes

Keywords

  • Drosophila
  • aging
  • amitosis
  • dedifferentiation
  • depolyploidization
  • injury
  • intestinal stem cell
  • midgut
  • regeneration
  • starvation

ASJC Scopus subject areas

  • Molecular Medicine
  • Genetics
  • Cell Biology

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