Limits...
Lrig1 expression defines a distinct multipotent stem cell population in mammalian epidermis.

Jensen KB, Collins CA, Nascimento E, Tan DW, Frye M, Itami S, Watt FM - Cell Stem Cell (2009)

Bottom Line: Lrig1 is a marker of human interfollicular epidermal stem cells and helps maintain stem cell quiescence.Lrig1 is a Myc target gene; loss of Lrig1 increases the proliferative capacity of stem cells in culture and results in epidermal hyperproliferation in vivo.Lrig1-expressing cells can give rise to all of the adult epidermal lineages in skin reconstitution assays.

View Article: PubMed Central - PubMed

Affiliation: Laboratory for Epidermal Stem Cell Biology, Wellcome Trust Centre for Stem Cell Research, University of Cambridge, Cambridge, UK.

ABSTRACT
Lrig1 is a marker of human interfollicular epidermal stem cells and helps maintain stem cell quiescence. We show that, in mouse epidermis, Lrig1 defines the hair follicle junctional zone adjacent to the sebaceous glands and infundibulum. Lrig1 is a Myc target gene; loss of Lrig1 increases the proliferative capacity of stem cells in culture and results in epidermal hyperproliferation in vivo. Lrig1-expressing cells can give rise to all of the adult epidermal lineages in skin reconstitution assays. However, during homeostasis and on retinoic acid stimulation, they are bipotent, contributing to the sebaceous gland and interfollicular epidermis. beta-catenin activation increases the size of the junctional zone compartment, and loss of Lrig1 causes a selective increase in beta-catenin-induced ectopic hair follicle formation in the interfollicular epidermis. Our results suggest that Lrig1-positive cells constitute a previously unidentified reservoir of adult mouse interfollicular epidermal stem cells.

Show MeSH

Related in: MedlinePlus

Characterization of Lrig1-Expressing Cells in Adult Epidermis(A–D) Immunofluorescence labeling of tail epidermal whole mounts from wild-type mice. Skin was in anagen (A) or telogen (B–D). Color coding indicates antibody labeling. Scale bars, 100 μm.(E) Flow cytometry of telogen epidermis from wild-type (WT) and Lrig1- (KO) epidermis disaggregated with thermolysin and labeled with antibodies to α6 integrin, Lrig1, CD34, and Sca1. Colored gates in top-right panel correspond to populations in lower-right panel and in (F) and (G).(F) Colony-forming efficiency of wild-type primary keratinocytes isolated as in (E).(G) Q-PCR of RNA from 105 wild-type epidermal cells isolated as in (E).(F and G) Data are means ± SEM (n = 4).
© Copyright Policy
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC2698066&req=5

fig2: Characterization of Lrig1-Expressing Cells in Adult Epidermis(A–D) Immunofluorescence labeling of tail epidermal whole mounts from wild-type mice. Skin was in anagen (A) or telogen (B–D). Color coding indicates antibody labeling. Scale bars, 100 μm.(E) Flow cytometry of telogen epidermis from wild-type (WT) and Lrig1- (KO) epidermis disaggregated with thermolysin and labeled with antibodies to α6 integrin, Lrig1, CD34, and Sca1. Colored gates in top-right panel correspond to populations in lower-right panel and in (F) and (G).(F) Colony-forming efficiency of wild-type primary keratinocytes isolated as in (E).(G) Q-PCR of RNA from 105 wild-type epidermal cells isolated as in (E).(F and G) Data are means ± SEM (n = 4).

Mentions: Lrig1-expressing cells in adult mouse epidermis were largely quiescent. In anagen, the zone of Lrig1 expression above the bulb separated the highly proliferative bulb cells from the rest of the outer-root sheath (Figure 1G). In the junctional zone of Lrig1-positive cells, there were fewer Ki67-positive cells than in the adjacent SGs (Figure 1H). In late anagen, the Lrig1-positive cells below the level of the SGs included DNA label-retaining cells, another indicator of quiescence (Braun et al., 2003; Figure 2A).


Lrig1 expression defines a distinct multipotent stem cell population in mammalian epidermis.

Jensen KB, Collins CA, Nascimento E, Tan DW, Frye M, Itami S, Watt FM - Cell Stem Cell (2009)

Characterization of Lrig1-Expressing Cells in Adult Epidermis(A–D) Immunofluorescence labeling of tail epidermal whole mounts from wild-type mice. Skin was in anagen (A) or telogen (B–D). Color coding indicates antibody labeling. Scale bars, 100 μm.(E) Flow cytometry of telogen epidermis from wild-type (WT) and Lrig1- (KO) epidermis disaggregated with thermolysin and labeled with antibodies to α6 integrin, Lrig1, CD34, and Sca1. Colored gates in top-right panel correspond to populations in lower-right panel and in (F) and (G).(F) Colony-forming efficiency of wild-type primary keratinocytes isolated as in (E).(G) Q-PCR of RNA from 105 wild-type epidermal cells isolated as in (E).(F and G) Data are means ± SEM (n = 4).
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2698066&req=5

fig2: Characterization of Lrig1-Expressing Cells in Adult Epidermis(A–D) Immunofluorescence labeling of tail epidermal whole mounts from wild-type mice. Skin was in anagen (A) or telogen (B–D). Color coding indicates antibody labeling. Scale bars, 100 μm.(E) Flow cytometry of telogen epidermis from wild-type (WT) and Lrig1- (KO) epidermis disaggregated with thermolysin and labeled with antibodies to α6 integrin, Lrig1, CD34, and Sca1. Colored gates in top-right panel correspond to populations in lower-right panel and in (F) and (G).(F) Colony-forming efficiency of wild-type primary keratinocytes isolated as in (E).(G) Q-PCR of RNA from 105 wild-type epidermal cells isolated as in (E).(F and G) Data are means ± SEM (n = 4).
Mentions: Lrig1-expressing cells in adult mouse epidermis were largely quiescent. In anagen, the zone of Lrig1 expression above the bulb separated the highly proliferative bulb cells from the rest of the outer-root sheath (Figure 1G). In the junctional zone of Lrig1-positive cells, there were fewer Ki67-positive cells than in the adjacent SGs (Figure 1H). In late anagen, the Lrig1-positive cells below the level of the SGs included DNA label-retaining cells, another indicator of quiescence (Braun et al., 2003; Figure 2A).

Bottom Line: Lrig1 is a marker of human interfollicular epidermal stem cells and helps maintain stem cell quiescence.Lrig1 is a Myc target gene; loss of Lrig1 increases the proliferative capacity of stem cells in culture and results in epidermal hyperproliferation in vivo.Lrig1-expressing cells can give rise to all of the adult epidermal lineages in skin reconstitution assays.

View Article: PubMed Central - PubMed

Affiliation: Laboratory for Epidermal Stem Cell Biology, Wellcome Trust Centre for Stem Cell Research, University of Cambridge, Cambridge, UK.

ABSTRACT
Lrig1 is a marker of human interfollicular epidermal stem cells and helps maintain stem cell quiescence. We show that, in mouse epidermis, Lrig1 defines the hair follicle junctional zone adjacent to the sebaceous glands and infundibulum. Lrig1 is a Myc target gene; loss of Lrig1 increases the proliferative capacity of stem cells in culture and results in epidermal hyperproliferation in vivo. Lrig1-expressing cells can give rise to all of the adult epidermal lineages in skin reconstitution assays. However, during homeostasis and on retinoic acid stimulation, they are bipotent, contributing to the sebaceous gland and interfollicular epidermis. beta-catenin activation increases the size of the junctional zone compartment, and loss of Lrig1 causes a selective increase in beta-catenin-induced ectopic hair follicle formation in the interfollicular epidermis. Our results suggest that Lrig1-positive cells constitute a previously unidentified reservoir of adult mouse interfollicular epidermal stem cells.

Show MeSH
Related in: MedlinePlus