TY - JOUR
T1 - The basement membrane of hair follicle stem cells is a muscle cell niche
AU - Fujiwara, Hironobu
AU - Ferreira, Manuela
AU - Donati, Giacomo
AU - Marciano, Denise K.
AU - Linton, James M.
AU - Sato, Yuya
AU - Hartner, Andrea
AU - Sekiguchi, Kiyotoshi
AU - Reichardt, Louis F.
AU - Watt, Fiona M.
N1 - Funding Information:
We thank Vladimir Botchkarev for K14-Noggin skin and Takako Sasaki for Fibulin-1 antibody. We gratefully acknowledge the technical assistance of the core resources of the CRUK Cambridge Research Institute. We thank the entire Watt lab for valuable reagents, suggestions, and advice. This work was funded by Cancer Research UK and supported by the University of Cambridge and Hutchison Whampoa Ltd. We also gratefully acknowledge financial support from the NIH (NS19090 to L.F.R.), from the Uehara Memorial Foundation (H.F.), and from EU FP7 (Optistem).
PY - 2011/2/18
Y1 - 2011/2/18
N2 - The hair follicle bulge in the epidermis associates with the arrector pili muscle (APM) that is responsible for piloerection ("goosebumps"). We show that stem cells in the bulge deposit nephronectin into the underlying basement membrane, thus regulating the adhesion of mesenchymal cells expressing the nephronectin receptor, α8β1 integrin, to the bulge. Nephronectin induces α8 integrin-positive mesenchymal cells to upregulate smooth muscle markers. In nephronectin knockout mice, fewer arrector pili muscles form in the skin, and they attach to the follicle above the bulge, where there is compensatory upregulation of the nephronectin family member EGFL6. Deletion of α8 integrin also abolishes selective APM anchorage to the bulge. Nephronectin is a Wnt target; epidermal β-catenin activation upregulates epidermal nephronectin and dermal α8 integrin expression. Thus, bulge stem cells, via nephronectin expression, create a smooth muscle cell niche and act as tendon cells for the APM. Our results reveal a functional role for basement membrane heterogeneity in tissue patterning.
AB - The hair follicle bulge in the epidermis associates with the arrector pili muscle (APM) that is responsible for piloerection ("goosebumps"). We show that stem cells in the bulge deposit nephronectin into the underlying basement membrane, thus regulating the adhesion of mesenchymal cells expressing the nephronectin receptor, α8β1 integrin, to the bulge. Nephronectin induces α8 integrin-positive mesenchymal cells to upregulate smooth muscle markers. In nephronectin knockout mice, fewer arrector pili muscles form in the skin, and they attach to the follicle above the bulge, where there is compensatory upregulation of the nephronectin family member EGFL6. Deletion of α8 integrin also abolishes selective APM anchorage to the bulge. Nephronectin is a Wnt target; epidermal β-catenin activation upregulates epidermal nephronectin and dermal α8 integrin expression. Thus, bulge stem cells, via nephronectin expression, create a smooth muscle cell niche and act as tendon cells for the APM. Our results reveal a functional role for basement membrane heterogeneity in tissue patterning.
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U2 - 10.1016/j.cell.2011.01.014
DO - 10.1016/j.cell.2011.01.014
M3 - Article
C2 - 21335239
AN - SCOPUS:79951716389
SN - 0092-8674
VL - 144
SP - 577
EP - 589
JO - Cell
JF - Cell
IS - 4
ER -