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Epidermal stem cells are retained in vivo throughout skin aging.

Giangreco A, Qin M, Pintar JE, Watt FM - Aging Cell (2008)

Bottom Line: In healthy individuals, skin integrity is maintained by epidermal stem cells which self-renew and generate daughter cells that undergo terminal differentiation.It is currently unknown whether epidermal stem cells influence or are affected by skin aging.We therefore compared young and aged skin stem cell abundance, organization, and proliferation.

View Article: PubMed Central - PubMed

Affiliation: Cancer Research UK, Cambridge Research Institute, Li Ka Shing Centre, Robinson Way, Cambridge CB2 0RE, UK. adam.giangreco@cancer.org.uk

ABSTRACT
In healthy individuals, skin integrity is maintained by epidermal stem cells which self-renew and generate daughter cells that undergo terminal differentiation. It is currently unknown whether epidermal stem cells influence or are affected by skin aging. We therefore compared young and aged skin stem cell abundance, organization, and proliferation. We discovered that despite age-associated differences in epidermal proliferation, dermal thickness, follicle patterning, and immune cell abundance, epidermal stem cells were maintained at normal levels throughout life. These findings, coupled with observed dermal gene expression changes, suggest that epidermal stem cells themselves are intrinsically aging resistant and that local environmental or systemic factors modulate skin aging.

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Epidermal stem cells are maintained during skin aging. (A, B) Representative epidermal whole mounts from young and old mice stained for keratin 14 (green) plus the stem cell marker keratin 15 (red) to identify hair follicle bulge stem cells. (C–E) Representative flow cytometry plots from 2-month-old (C), 6-month-old (D), and 22-month-old (E) murine epidermal skin preparations stained for CD34-PE and α6 integrin–FITC. Three distinct epidermal populations are shown: α6(+) basal cells (blue gate), α6(+)/CD34(+) stem cells (orange gate), and α6(dim)/CD34(+) cells (grey gate). (F) Quantification of the per cent of viable cells represented within the α6(+) gated population from epidermal preparations of n = 3 mice/age at each of 2 months, 6 months, 12 months, 18 months, or 22 months. (G) Quantification of the per cent of viable cells represented as α6(+)/CD34(+) stem cell (orange bars) or α6(dim)/CD34(+) stem cell (grey bars) populations. No significant differences in stem cell abundance were observed between 6 months and 22 months age. (H) Quantitative polymerase chain reaction analysis of whole-skin RNA for α6 (black bars) and keratin 15 (green bars) levels in 2-month-old, 6-month-old, 18-month-old, and 22-month-old mice. Scale bars = 100 µm (A, B). Asterisk (G, H) indicates significant difference versus 2-month sample; P < 0.05.
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fig02: Epidermal stem cells are maintained during skin aging. (A, B) Representative epidermal whole mounts from young and old mice stained for keratin 14 (green) plus the stem cell marker keratin 15 (red) to identify hair follicle bulge stem cells. (C–E) Representative flow cytometry plots from 2-month-old (C), 6-month-old (D), and 22-month-old (E) murine epidermal skin preparations stained for CD34-PE and α6 integrin–FITC. Three distinct epidermal populations are shown: α6(+) basal cells (blue gate), α6(+)/CD34(+) stem cells (orange gate), and α6(dim)/CD34(+) cells (grey gate). (F) Quantification of the per cent of viable cells represented within the α6(+) gated population from epidermal preparations of n = 3 mice/age at each of 2 months, 6 months, 12 months, 18 months, or 22 months. (G) Quantification of the per cent of viable cells represented as α6(+)/CD34(+) stem cell (orange bars) or α6(dim)/CD34(+) stem cell (grey bars) populations. No significant differences in stem cell abundance were observed between 6 months and 22 months age. (H) Quantitative polymerase chain reaction analysis of whole-skin RNA for α6 (black bars) and keratin 15 (green bars) levels in 2-month-old, 6-month-old, 18-month-old, and 22-month-old mice. Scale bars = 100 µm (A, B). Asterisk (G, H) indicates significant difference versus 2-month sample; P < 0.05.

Mentions: The observation that the ‘bulge’ region was retained prompted us to examine whether epidermal stem cell abundance was altered within aged skin. To determine this, we performed whole-mount immunostaining using antibodies directed against the bulge stem cell protein keratin 15 (Liu et al., 2003). Despite age-associated follicular morphological changes (first described in Fig. 1), we determined that keratin 15(+) bulge stem cells were retained in follicles of both young and old mice (Fig. 2A,B).


Epidermal stem cells are retained in vivo throughout skin aging.

Giangreco A, Qin M, Pintar JE, Watt FM - Aging Cell (2008)

Epidermal stem cells are maintained during skin aging. (A, B) Representative epidermal whole mounts from young and old mice stained for keratin 14 (green) plus the stem cell marker keratin 15 (red) to identify hair follicle bulge stem cells. (C–E) Representative flow cytometry plots from 2-month-old (C), 6-month-old (D), and 22-month-old (E) murine epidermal skin preparations stained for CD34-PE and α6 integrin–FITC. Three distinct epidermal populations are shown: α6(+) basal cells (blue gate), α6(+)/CD34(+) stem cells (orange gate), and α6(dim)/CD34(+) cells (grey gate). (F) Quantification of the per cent of viable cells represented within the α6(+) gated population from epidermal preparations of n = 3 mice/age at each of 2 months, 6 months, 12 months, 18 months, or 22 months. (G) Quantification of the per cent of viable cells represented as α6(+)/CD34(+) stem cell (orange bars) or α6(dim)/CD34(+) stem cell (grey bars) populations. No significant differences in stem cell abundance were observed between 6 months and 22 months age. (H) Quantitative polymerase chain reaction analysis of whole-skin RNA for α6 (black bars) and keratin 15 (green bars) levels in 2-month-old, 6-month-old, 18-month-old, and 22-month-old mice. Scale bars = 100 µm (A, B). Asterisk (G, H) indicates significant difference versus 2-month sample; P < 0.05.
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Related In: Results  -  Collection

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fig02: Epidermal stem cells are maintained during skin aging. (A, B) Representative epidermal whole mounts from young and old mice stained for keratin 14 (green) plus the stem cell marker keratin 15 (red) to identify hair follicle bulge stem cells. (C–E) Representative flow cytometry plots from 2-month-old (C), 6-month-old (D), and 22-month-old (E) murine epidermal skin preparations stained for CD34-PE and α6 integrin–FITC. Three distinct epidermal populations are shown: α6(+) basal cells (blue gate), α6(+)/CD34(+) stem cells (orange gate), and α6(dim)/CD34(+) cells (grey gate). (F) Quantification of the per cent of viable cells represented within the α6(+) gated population from epidermal preparations of n = 3 mice/age at each of 2 months, 6 months, 12 months, 18 months, or 22 months. (G) Quantification of the per cent of viable cells represented as α6(+)/CD34(+) stem cell (orange bars) or α6(dim)/CD34(+) stem cell (grey bars) populations. No significant differences in stem cell abundance were observed between 6 months and 22 months age. (H) Quantitative polymerase chain reaction analysis of whole-skin RNA for α6 (black bars) and keratin 15 (green bars) levels in 2-month-old, 6-month-old, 18-month-old, and 22-month-old mice. Scale bars = 100 µm (A, B). Asterisk (G, H) indicates significant difference versus 2-month sample; P < 0.05.
Mentions: The observation that the ‘bulge’ region was retained prompted us to examine whether epidermal stem cell abundance was altered within aged skin. To determine this, we performed whole-mount immunostaining using antibodies directed against the bulge stem cell protein keratin 15 (Liu et al., 2003). Despite age-associated follicular morphological changes (first described in Fig. 1), we determined that keratin 15(+) bulge stem cells were retained in follicles of both young and old mice (Fig. 2A,B).

Bottom Line: In healthy individuals, skin integrity is maintained by epidermal stem cells which self-renew and generate daughter cells that undergo terminal differentiation.It is currently unknown whether epidermal stem cells influence or are affected by skin aging.We therefore compared young and aged skin stem cell abundance, organization, and proliferation.

View Article: PubMed Central - PubMed

Affiliation: Cancer Research UK, Cambridge Research Institute, Li Ka Shing Centre, Robinson Way, Cambridge CB2 0RE, UK. adam.giangreco@cancer.org.uk

ABSTRACT
In healthy individuals, skin integrity is maintained by epidermal stem cells which self-renew and generate daughter cells that undergo terminal differentiation. It is currently unknown whether epidermal stem cells influence or are affected by skin aging. We therefore compared young and aged skin stem cell abundance, organization, and proliferation. We discovered that despite age-associated differences in epidermal proliferation, dermal thickness, follicle patterning, and immune cell abundance, epidermal stem cells were maintained at normal levels throughout life. These findings, coupled with observed dermal gene expression changes, suggest that epidermal stem cells themselves are intrinsically aging resistant and that local environmental or systemic factors modulate skin aging.

Show MeSH
Related in: MedlinePlus