Transit-amplifying progenitor with maturation-dependent behavior contributes to epidermal renewal

• DOI: 10.1101/2022.06.12.495812
• Publication Date: 2022-06-16T05:20:10Z
• Authors: Sangeeta Ghuwalewala; Kevin Jiang; Sara Ragi; David Shalloway; Tudorita Tumbar
• Keywords: 0301 basic medicine; 03 medical and health sciences

AbstractTransit-amplifying progenitor populations with phased behavior have long been postulated as essential to epidermal renewal, but not experimentally observed in vivo. Here we identify a population with bi-phasic behavior using CreER genetic cell-marking in mice for long-term lineage tracing and clonal analysis. Nascent, highly expressing Aspm cells undergo an amplification-phase followed by a timed transition into an extinction-phase, with near complete loss of descending cells from skin. Generalized birth-death modeling of Aspm-CreER and a Dlx1-CreER population that behaves like a stem cell demonstrates neutral competition for both populations, but neutral drift only for the stem cells. This work identifies a long-missing class of non-self-renewing epidermal progenitors with bi-phasic behavior that appears time-dependent as the lineage matures, indicative of a transit-amplifying cell. This has broad implications for understanding cell fate decisions and tissue renewal mechanisms.One-sentence summaryWe identify a long-missing class of non-self-renewing epidermal progenitors with bi-phasic and maturation-dependent behavior in vivo.