A functional role of RB-dependent pathway in the control of quiescence in adult epidermal stem cells revealed by genomic profiling.
Continuous cell renewal in mouse epidermis is at the expense of a pool of pluripotent cells that lie in a well defined niche in the hair follicle known as the bulge. To identify mechanisms controlling hair follicle stem cell homeostasis, we developed a strategy to isolate adult bulge stem cells in mice and to define their transcriptional profile. We observed that a large number of transcripts are underexpressed in hair follicle stem cells when compared to non-stem cells. Importantly, the majority of these downregulated genes are involved in cell cycle. Using bioinformatics tools, we identified the E2F transcription factor family as a potential element involved in the regulation of these transcripts. To determine their functional role, we used engineered mice lacking Rb gene in epidermis, which showed increased expression of most E2F family members and increased E2F transcriptional activity. Experiments designed to analyze epidermal stem cell functionality (i.e.: hair regrowth and wound healing) imply a role of the Rb-E2F axis in the control of stem cell quiescence in epidermis.
Lorz
Corina
C
Unidad de Oncología Molecular, División de Biomedicina Epitelial, Departamento de Investigación Básica, Centro de Investigaciones Energéticas, Medioambientales y Tecnológicas (CIEMAT), Edificio 70a, CIEMAT, Ave. Complutense 22, 28040, Madrid, Spain.
García-Escudero
Ramón
R
Segrelles
Carmen
C
Garín
Marina I
MI
Ariza
José M
JM
Santos
Mirentxu
M
Ruiz
Sergio
S
Lara
María F
MF
Martínez-Cruz
Ana B
AB
Costa
Clotilde
C
Buitrago-Pérez
Agueda
A
Saiz-Ladera
Cristina
C
Dueñas
Marta
M
Paramio
Jesús M
JM
D000818:Animals; D002478:Cells, Cultured; D020869:Gene Expression Profiling; D018859:Hair Follicle / Q000166:cytology*; D051379:Mice; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology*; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism*