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

Lrig1 Expression Defines a Distinct Population of Epidermal Cells in the Junctional Zone(A–H) Immunofluorescence labeling of sections of embryonic (A) and adult back (C) and tail (D) skin and whole mounts of embryonic (B) and adult (E–H) tail epidermis. Adult skin was in telogen (C–F and H) or early anagen (G). Skin was from wild-type (A, B, upper panel of C, D, E, G, and H) or Lrig1- mice (lower panel of C, F).Insert in (G) shows the bulb at a higher magnification. Color coding indicates antibody labeling. Dashed lines represent the boundary between dermis and epidermis (A and C) or demarcate hair follicles (B and G).epi, epidermis; de, dermis; IFE, interfollicular epidermis; SG, sebaceous gland; JZ, junctional zone; BU, bulge; BB, bulb; HFSC, developing hair follicle stem cell compartment; PL, hair follicle placode; HG, hair germ. (A) is shown at a higher magnification in Figures S1F–S1H. Scale bars, 25 μm (A and D) and 100 μm (B and E–H).(I) Diagram illustrating the different regions of adult epidermis. Red, junctional zone; green, bulge.
© Copyright Policy
Related In: Results  -  Collection

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

fig1: Lrig1 Expression Defines a Distinct Population of Epidermal Cells in the Junctional Zone(A–H) Immunofluorescence labeling of sections of embryonic (A) and adult back (C) and tail (D) skin and whole mounts of embryonic (B) and adult (E–H) tail epidermis. Adult skin was in telogen (C–F and H) or early anagen (G). Skin was from wild-type (A, B, upper panel of C, D, E, G, and H) or Lrig1- mice (lower panel of C, F).Insert in (G) shows the bulb at a higher magnification. Color coding indicates antibody labeling. Dashed lines represent the boundary between dermis and epidermis (A and C) or demarcate hair follicles (B and G).epi, epidermis; de, dermis; IFE, interfollicular epidermis; SG, sebaceous gland; JZ, junctional zone; BU, bulge; BB, bulb; HFSC, developing hair follicle stem cell compartment; PL, hair follicle placode; HG, hair germ. (A) is shown at a higher magnification in Figures S1F–S1H. Scale bars, 25 μm (A and D) and 100 μm (B and E–H).(I) Diagram illustrating the different regions of adult epidermis. Red, junctional zone; green, bulge.

Mentions: At E14.5, prior to HF placode formation, Lrig1 was expressed at low levels in dorsal epidermis and at higher levels by a subpopulation of dermal cells (Figure S1A available online). At E17.5 and E18.5, Lrig1 expression was upregulated in the P-cadherin dim population of multipotent stem cells in the developing HF (Nowak et al., 2008) and was absent from the P-cadherin bright cells at the base (Figures 1A, S1B, and S1F–S1H). Thus, during development, the presumptive bulge stem cell population expressed Lrig1. This expression pattern persisted at P1, except that from then onward, dermal expression was reduced (Figure S1C). Q-PCR of RNA isolated from back skin samples (Figure S1D) revealed that Lrig1 levels peaked at P1.


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)

Lrig1 Expression Defines a Distinct Population of Epidermal Cells in the Junctional Zone(A–H) Immunofluorescence labeling of sections of embryonic (A) and adult back (C) and tail (D) skin and whole mounts of embryonic (B) and adult (E–H) tail epidermis. Adult skin was in telogen (C–F and H) or early anagen (G). Skin was from wild-type (A, B, upper panel of C, D, E, G, and H) or Lrig1- mice (lower panel of C, F).Insert in (G) shows the bulb at a higher magnification. Color coding indicates antibody labeling. Dashed lines represent the boundary between dermis and epidermis (A and C) or demarcate hair follicles (B and G).epi, epidermis; de, dermis; IFE, interfollicular epidermis; SG, sebaceous gland; JZ, junctional zone; BU, bulge; BB, bulb; HFSC, developing hair follicle stem cell compartment; PL, hair follicle placode; HG, hair germ. (A) is shown at a higher magnification in Figures S1F–S1H. Scale bars, 25 μm (A and D) and 100 μm (B and E–H).(I) Diagram illustrating the different regions of adult epidermis. Red, junctional zone; green, bulge.
© Copyright Policy
Related In: Results  -  Collection

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

fig1: Lrig1 Expression Defines a Distinct Population of Epidermal Cells in the Junctional Zone(A–H) Immunofluorescence labeling of sections of embryonic (A) and adult back (C) and tail (D) skin and whole mounts of embryonic (B) and adult (E–H) tail epidermis. Adult skin was in telogen (C–F and H) or early anagen (G). Skin was from wild-type (A, B, upper panel of C, D, E, G, and H) or Lrig1- mice (lower panel of C, F).Insert in (G) shows the bulb at a higher magnification. Color coding indicates antibody labeling. Dashed lines represent the boundary between dermis and epidermis (A and C) or demarcate hair follicles (B and G).epi, epidermis; de, dermis; IFE, interfollicular epidermis; SG, sebaceous gland; JZ, junctional zone; BU, bulge; BB, bulb; HFSC, developing hair follicle stem cell compartment; PL, hair follicle placode; HG, hair germ. (A) is shown at a higher magnification in Figures S1F–S1H. Scale bars, 25 μm (A and D) and 100 μm (B and E–H).(I) Diagram illustrating the different regions of adult epidermis. Red, junctional zone; green, bulge.
Mentions: At E14.5, prior to HF placode formation, Lrig1 was expressed at low levels in dorsal epidermis and at higher levels by a subpopulation of dermal cells (Figure S1A available online). At E17.5 and E18.5, Lrig1 expression was upregulated in the P-cadherin dim population of multipotent stem cells in the developing HF (Nowak et al., 2008) and was absent from the P-cadherin bright cells at the base (Figures 1A, S1B, and S1F–S1H). Thus, during development, the presumptive bulge stem cell population expressed Lrig1. This expression pattern persisted at P1, except that from then onward, dermal expression was reduced (Figure S1C). Q-PCR of RNA isolated from back skin samples (Figure S1D) revealed that Lrig1 levels peaked at P1.

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