TY - JOUR T1 - Gradual differentiation uncoupled from cell cycle exit generates heterogeneity in the epidermal stem cell layer JF - bioRxiv DO - 10.1101/2021.01.07.425777 SP - 2021.01.07.425777 AU - Katie Cockburn AU - Karl Annusver AU - Smirthy Ganesan AU - Kailin R. Mesa AU - Kyogo Kawaguchi AU - Maria Kasper AU - Valentina Greco Y1 - 2021/01/01 UR - http://biorxiv.org/content/early/2021/01/07/2021.01.07.425777.abstract N2 - High turnover tissues continually lose specialized cells that are replaced by stem cell activity. In the adult mammalian epidermis, it is unclear how molecularly heterogenous stem/progenitor cell populations fit into the complete trajectory of epidermal differentiation. We show that differentiation, from commitment to exit from the stem cell layer, is a multi-day process wherein cells transit through a continuum of transcriptional changes. Differentiation-committed cells remain capable of dividing to produce daughter cells fated to further differentiate, demonstrating that differentiation is uncoupled from cell cycle exit. These cell divisions are not required as part of an obligate transit amplifying program but instead protect density in the stem cell layer. Thus, instead of distinct contributions from multiple progenitors, a continuous gradual differentiation process fuels homeostatic epidermal turnover.One sentence summary Heterogeneity in the epidermal stem cell layer reflects a gradual differentiation program that is uncoupled from the loss of proliferative capacity.Competing Interest StatementThe authors have declared no competing interest. ER -