• Aiko Sada

SAM mouse model for epidermal stem cell aging (Changarathil G et al., PLoS One, 2019)

Our new paper is now available online.

Changarathil G, Ramirez K, Isoda H, Sada A*, Yanagisawa H: Wild-type and SAMP8 mice show age-dependent changes in distinct stem cell compartments of the interfollicular epidermis. 

* Corresponding author

PLoS One 14(5): e0215908​, 2019 [PubMed] [Full Text]

This work is mainly done by Gopu Changarathil, a Ph.D. student in Graduate School of Comprehensive Human Sciences, University of Tsukuba. Congrats!

Karina Ramirez, a Ph.D. student in Ph.D. Program in Human Biology, also contributed greatly to this work.

I would like to thank my collaborator Dr. Isoda and my mentor Dr. Yanagisawa, for their intellectual input and continued support!

For me, this is my first paper as a corresponding author, and also a first paper after coming back to Japan. I will keep going!

Summary of this work

The aged skin shows reduced wound healing and barrier function, with an increased risk of cancer, which may be caused by dysfunction or misregulation of epidermal stem cells during aging. A classical model predicts that tissue stem cells divide less frequently than their immediate daughter cells to protect themselves from accumulating genetic mutations, telomere-shortening or aging. Contradicting to this model, our recent study proposed the co-existence of two distinct stem cell populations – slow-cycling and fast-dividing stem cells – in the mouse epidermis, which possess self-renewal and differentiation capacities with distinct molecular profiles and spatial territories (Sada et al, Nat. Cell. Biol.2016). However, it remains largely unknown how aging affects these two stem cell populations and how these changes contribute to age-associated tissue dysfunction.

In this manuscript, we provide comprehensive characterization of age-related changes of the mouse epidermis and suggest that distinct stem cell populations may react differently to aging. Fast-dividing stem cells show a significant decrease in proliferation along with structural changes, including irregular undulations and overall thinning of the epidermis. In contrast, differentiation process is more affected in the slow-cycling stem cell lineage. Moreover, we find that SAMP8 (senescence-accelerated mouse prone 8) exhibit premature age-dependent epidermal phenotypessimilar to aged wild-type mice, suggesting the potential use of this mouse as a new tool for understanding the aging process of the epidermis and its stem cells.

Aiko Sada