Progenitor Function in Self-Renewing Human Epidermis is Maintained by the Exosome

Stem and progenitor cells maintain the tissue they reside in for life by regulating the balance between proliferation and differentiation. How this is done is not well understood. Here, we report that the human exosome maintains progenitor cell function. The expression of several subunits of the exosome were found to be enriched in epidermal progenitor cells, which were required to retain proliferative capacity and to prevent premature differentiation. Loss of PM/Scl-75 also known as EXOSC9, a key subunit of the exosome complex, resulted in loss of cells from the progenitor cell compartment, premature differentiation, and loss of epidermal tissue. EXOSC9 promotes self-renewal and prevents premature differentiation by maintaining transcript levels of a transcription factor necessary for epidermal differentiation, GRHL3, at low levels through mRNA degradation. These data demonstrate that control of differentiation specific transcription factors through mRNA degradation is required for progenitor cell maintenance in mammalian tissue. [Display omitted] ► EXOSC9 expression is high in progenitors but decreases upon differentiation ► EXOSC9 is necessary for the maintenance of epidermal progenitor cells ► Exosome function regulates gene expression and self-renewal ► The underlying mechanism involves degradation of GHRL3 transcripts mRNA degradation by the exosome complex plays an important role in the maintenance of self renewal and progenitor function in the human epidermis.