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

TY - JOUR

T1 - Lrig1 expression defines a distinct multipotent stem cell population in mammalian epidermis

AU - Jensen, Kim B

AU - Collins, Charlotte A

AU - Nascimento, Elisabete

AU - Tan, David W

AU - Frye, Michaela

AU - Itami, Satoshi

AU - Watt, Fiona M

PY - 2009/5/8

Y1 - 2009/5/8

N2 - 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.

AB - 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.

KW - Animals

KW - Cell Differentiation

KW - Cell Lineage

KW - Cell Proliferation

KW - Epidermis

KW - Hair Follicle

KW - Mammals

KW - Membrane Glycoproteins

KW - Mice

KW - Mice, Transgenic

KW - Multipotent Stem Cells

KW - Nerve Tissue Proteins

KW - Proto-Oncogene Proteins c-myc

KW - beta Catenin

U2 - 10.1016/j.stem.2009.04.014

DO - 10.1016/j.stem.2009.04.014

M3 - Journal article

C2 - 19427292

SN - 1934-5909

VL - 4

SP - 427

EP - 439

JO - Cell Stem Cell

JF - Cell Stem Cell

IS - 5

ER -