A transit-amplifying progenitor with biphasic behavior contributes to epidermal renewal

Area of Science:

• Dermatology
• Developmental Biology
• Stem Cell Biology

Background:

• Transit-amplifying (TA) cells are progenitors with a defined amplification phase before extinction.
• A biphasic epidermal TA progenitor, exhibiting both amplification and extinction, has been long postulated but not experimentally observed in vivo.
• Understanding progenitor cell dynamics is crucial for tissue renewal and repair mechanisms.

Purpose of the Study:

• To experimentally identify and characterize a biphasic transit-amplifying progenitor population in the adult epidermis in vivo.
• To investigate the proliferative behavior and lineage dynamics of this newly identified TA progenitor population.
• To develop and apply a novel modeling approach for analyzing progenitor cell behavior with age-dependent changes.

Main Methods:

• Clonal analysis using Aspm-CreER genetic cell-marking in mice for lineage tracing.
• Comparison of cell division rates between Aspm-CreER-marked TA cells and Dlx1-CreER-marked stem cells.
• Development and application of generalized birth-death modeling for long-term lineage tracing data analysis.

Main Results:

• Identification of a novel TA progenitor population in adult mouse skin contributing to both homeostasis and injury repair.
• This TA population exhibits more frequent cell division compared to long-term self-renewing stem cells.
• Birth-death modeling revealed neutral competition in both TA progenitors and stem cells, with neutral drift observed only in stem cells.
• Quantitative analysis demonstrated that TA progenitors amplify the basal layer before transitioning, with the homeostatic TA population predominantly in the extinction phase.

Conclusions:

• This study identifies a long-sought class of non-self-renewing, biphasic epidermal TA progenitors.
• The findings provide experimental evidence for biphasic behavior in epidermal progenitors in vivo.
• The developed modeling framework is broadly applicable to analyzing progenitor cells with age-dependent behavioral changes, advancing the understanding of tissue renewal.