title: FoxO is a critical regulator of stem cell maintenance in immortal Hydra.
abstract: Hydra's unlimited life span has long attracted attention from natural scientists. The reason for that phenomenon is the indefinite self-renewal capacity of its stem cells. The underlying molecular mechanisms have yet to be explored. Here, by comparing the transcriptomes of Hydra's stem cells followed by functional analysis using transgenic polyps, we identified the transcription factor forkhead box O (FoxO) as one of the critical drivers of this continuous self-renewal. foxO overexpression increased interstitial stem cell and progenitor cell proliferation and activated stem cell genes in terminally differentiated somatic cells. foxO down-regulation led to an increase in the number of terminally differentiated cells, resulting in a drastically reduced population growth rate. In addition, it caused down-regulation of stem cell genes and antimicrobial peptide (AMP) expression. These findings contribute to a molecular understanding of Hydra's immortality, indicate an evolutionarily conserved role of FoxO in controlling longevity from Hydra to humans, and have implications for understanding cellular aging.
authors.affiliation: Zoological Institute,  Christian-Albrechts-University, 24098 Kiel,  Germany.
authors.forename: Anna-Marei
authors.initials: AM
authors.lastname: Boehm
authors.forename: Konstantin
authors.initials: K
authors.lastname: Khalturin
authors.forename: Friederike
authors.initials: F
authors.lastname: Anton-Erxleben
authors.forename: Georg
authors.initials: G
authors.lastname: Hemmrich
authors.forename: Ulrich C
authors.initials: UC
authors.lastname: Klostermeier
authors.forename: Javier A
authors.initials: JA
authors.lastname: Lopez-Quintero
authors.forename: Hans-Heinrich
authors.initials: HH
authors.lastname: Oberg
authors.forename: Malte
authors.initials: M
authors.lastname: Puchert
authors.forename: Philip
authors.initials: P
authors.lastname: Rosenstiel
authors.forename: Jörg
authors.initials: J
authors.lastname: Wittlieb
authors.forename: Thomas C G
authors.initials: TC
authors.lastname: Bosch
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D019070:Cell Lineage; D051858:Forkhead Transcription Factors / Q000235:genetics / Q000502:physiology*; D020868:Gene Silencing; D006829:Hydra / Q000166:cytology* / Q000276:immunology / Q000378:metabolism; D007113:Immunity, Innate; D008969:Molecular Sequence Data; D013234:Stem Cells / Q000378:metabolism*
chemical_list: D051858:Forkhead Transcription Factors