Spindle checkpoint deficiency is tolerated by murine epidermal cells but not hair follicle stem cells

Floris Foijer, Tia Marie Ditommaso, Giacomo Donati, Katta Hautaviita, Stephanie Z Xie, Emma Heath, Ian Macleod Smyth, Fiona M Watt, Peter K Sorger, Allan Bradley

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36 Citations (Scopus)

Abstract

The spindle assembly checkpoint (SAC) ensures correct chromosome segregation during mitosis by preventing aneuploidy, an event that is detrimental to the fitness and survival of normal cells but oncogenic in tumor cells. Deletion of SAC genes is incompatible with early mouse development, and RNAi-mediated depletion of SAC components in cultured cells results in rapid death. Here we describe the use of a conditional KO of mouse Mad2, an essential component of the SAC signaling cascade, as a means to selectively induce chromosome instability and aneuploidy in the epidermis of the skin. We observe that SAC inactivation is tolerated by interfollicular epidermal cells but results in depletion of hair follicle bulge stem cells. Eventually, a histologically normal epidermis develops within approximately 1 mo after birth, albeit without any hair. Mad2-deficient cells in this epidermis exhibited abnormal transcription of metabolic genes, consistent with aneuploid cell state. Hair follicle bulge stem cells were completely absent, despite the continued presence of rudimentary hair follicles. These data demonstrate that different cell lineages within a single tissue respond differently to chromosome instability: some proliferating cell lineages can survive, but stem cells are highly sensitive.
Original languageEnglish
Pages (from-to)2928 - 2933
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume110
Issue number8
DOIs
Publication statusPublished - 2013

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