Distinct fibroblast lineages determine dermal architecture in skin development and repair
Top Cited Papers
Open Access
- 11 December 2013
- journal article
- research article
- Published by Springer Science and Business Media LLC in Nature
- Vol. 504 (7479), 277-+
- https://doi.org/10.1038/nature12783
Abstract
Fibroblasts are the major mesenchymal cell type in connective tissue and deposit the collagen and elastic fibres of the extracellular matrix (ECM)(1). Even within a single tissue, fibroblasts exhibit considerable functional diversity, but it is not known whether this reflects the existence of a differentiation hierarchy or is a response to different environmental factors. Here we show, using transplantation assays and lineage tracing in mice, that the fibroblasts of skin connective tissue arise from two distinct lineages. One forms the upper dermis, including the dermal papilla that regulates hair growth and the arrector pili muscle, which controls piloerection. The other forms the lower dermis, including the reticular fibroblasts that synthesize the bulk of the fibrillar ECM, and the preadipocytes and adipocytes of the hypodermis. The upper lineage is required for hair follicle formation. In wounded adult skin, the initial wave of dermal repair is mediated by the lower lineage and upper dermal fibroblasts are recruited only during re-epithelialization. Epidermal beta-catenin activation stimulates the expansion of the upper dermal lineage, rendering wounds permissive for hair follicle formation. Our findings explain why wounding is linked to formation of ECM-rich scar tissue that lacks hair follicles(2-4). They also forma platform for discovering fibroblast lineages in other tissues and for examining fibroblast changes in ageing and disease.Keywords
This publication has 30 references indexed in Scilit:
- Sox2 modulates the function of two distinct cell lineages in mouse skinDevelopmental Biology, 2013
- The Epidermis Comprises Autonomous Compartments Maintained by Distinct Stem Cell PopulationsCell Stem Cell, 2013
- The Interfollicular Epidermis of Adult Mouse Tail Comprises Two Distinct Cell Lineages that Are Differentially Regulated by Wnt, Edaradd, and Lrig1Stem Cell Reports, 2013
- Clonal Growth of Dermal Papilla Cells in Hydrogels Reveals Intrinsic Differences between Sox2-Positive and -Negative Cells In Vitro and In VivoJournal of Investigative Dermatology, 2012
- Adipocyte Lineage Cells Contribute to the Skin Stem Cell Niche to Drive Hair CyclingCell, 2011
- Tumor formation initiated by nondividing epidermal cells via an inflammatory infiltrateProceedings of the National Academy of Sciences of the United States of America, 2010
- Cyclic dermal BMP signalling regulates stem cell activation during hair regenerationNature, 2008
- Epidermal terminal differentiation depends on B lymphocyte-induced maturation protein-1Proceedings of the National Academy of Sciences of the United States of America, 2007
- Blimp1 Defines a Progenitor Population that Governs Cellular Input to the Sebaceous GlandCell, 2006
- Fibroblasts in cancerNature Reviews Cancer, 2006