Wild-type and SAMP8 mice show age-dependent changes in distinct stem cell compartments of the interfollicular epidermis

Abstract

Delayed wound healing and reduced barrier function with an increased risk of cancer are characteristics of aged skin and one possible mechanism is misregulation or dysfunction of epidermal stem cells during aging. Recent studies have identified heterogeneous stem cell populations within the mouse interfollicular epidermis that are defined by territorial distribution and cell division frequency; however, it is unknown whether the individual stem cell populations undergo distinct aging processes. Here we provide comprehensive characterization of age-related changes in the mouse epidermis within the specific territories of slow-cycling and fast-dividing stem cells using old wild-type, senescence-accelerated mouse prone 1 (SAMP1) and SAMP8 mice. During aging, the epidermis exhibits structural changes such as irregular micro-undulations and overall thinning of the tissue. We also find that, in the old epidermis, proliferation is preferentially decreased in the region where fast-dividing stem cells reside whereas the lineage differentiation marker appears to be more affected in the slow-cycling stem cell region. Furthermore, SAMP8, but not SAMP1, exhibits precocious aging similar to that of aged wild-type mice, suggesting a potential use of this model for aging study of the epidermis and its stem cells. Taken together, our study reveals distinct aging processes governing the two epidermal stem cell populations and suggests a potential mechanism in differential responses of compartmentalized stem cells and their niches to aging.

Enhancement of elastin expression by transdermal administration of sialidase isozyme Neu2

“…SAMP8 strain is characterized by Alzheimer's disease-like neurodegenerative and cognitive deficit and a circadian rhythm disorder 30,31 . SAMP8 mice exhibit precocious aging similar to that of aged wild-type mice 32 .…”

Glycome profiling by lectin microarray reveals dynamic glycan alterations during epidermal stem cell aging

“…An age‐related decline in tissue regeneration and function could be attributed to an impaired stem cell function, a theory known as “stem cell aging” (López‐Otín, Blasco, Partridge, Serrano, & Kroemer, 2013); however, it remains elusive what are the crucial drivers for aging at cellular and molecular levels. An aged epidermis shows histological and functional changes, including a decreased proliferative capacity (Charruyer et al, 2009; Gilchrest, 1983) and lower success in epidermal engraftment (Piccin & Morshead, 2010), a decrease in epidermal thickness, flattening of epidermal–dermal junction (Changarathil, Ramirez, Isoda, Sada, & Yanagisawa, 2019; Giangreco, Goldie, Failla, Saintigny, & Watt, 2010; Langton, Halai, Griffiths, Sherratt, & Watson, 2016; Makrantonaki & Zouboulis, 2007), delayed wound healing (Keyes et al, 2016), decreased barrier function (Gonzales & Fuchs, 2017), increased risk of cancer (Adams, Jasper, & Rudolph, 2015; López‐Otín et al, 2013), impaired HF stem cell lineages (Matsumura et al, 2016), and interaction with their niche (Ge et al, 2020). Mutant mouse studies and transcriptome analyses have suggested that the age‐related epidermal dysfunction could be due to defects in IFE and HF stem cells to interact with other cell types or extracellular matrix in skin (Ge et al, 2020; Giangreco, Qin, Pintar, & Watt, 2008; Keyes et al, 2016; Liu et al, 2019; Matsumura et al, 2016; Watanabe et al, 2017).…”

The extracellular matrix fibulin 7 maintains epidermal stem cell heterogeneity during skin aging

“…Since basal cells in the scale proliferate less than those in the interscale (Changarathil et al ., 2019; Giangreco et al , 2008), separation by cell division frequency in the H2B-GFP system became more ambiguous in aged mice and may not exactly represent the same stem cell populations in the young mice. Furthermore, the loss of Slc1a3 CreER + fast-cycling stem cell clones during aging made it difficult to isolate the same stem cell population labeled at younger ages.…”