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Fibroblast heterogeneity: implications for human disease
Magnus D. Lynch, Fiona M. Watt
Magnus D. Lynch, Fiona M. Watt
Published January 2, 2018
Citation Information: J Clin Invest. 2018;128(1):26-35. https://doi.org/10.1172/JCI93555.
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Review Series

Fibroblast heterogeneity: implications for human disease

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Abstract

Fibroblasts synthesize the extracellular matrix of connective tissue and play an essential role in maintaining the structural integrity of most tissues. Researchers have long suspected that fibroblasts exhibit functional specialization according to their organ of origin, body site, and spatial location. In recent years, a number of approaches have revealed the existence of fibroblast subtypes in mice. Here, we discuss fibroblast heterogeneity with a focus on the mammalian dermis, which has proven an accessible and tractable system for the dissection of these relationships. We begin by considering differences in fibroblast identity according to anatomical site of origin. Subsequently, we discuss new results relating to the existence of multiple fibroblast subtypes within the mouse dermis. We consider the developmental origin of fibroblasts and how this influences heterogeneity and lineage restriction. We discuss the mechanisms by which fibroblast heterogeneity arises, including intrinsic specification by transcriptional regulatory networks and epigenetic factors in combination with extrinsic effects of the spatial context within tissue. Finally, we discuss how fibroblast heterogeneity may provide insights into pathological states including wound healing, fibrotic diseases, and aging. Our evolving understanding suggests that ex vivo expansion or in vivo inhibition of specific fibroblast subtypes may have important therapeutic applications.

Authors

Magnus D. Lynch, Fiona M. Watt

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Figure 1

Structure of murine dorsal skin.

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Structure of murine dorsal skin.
The skin has two layers, the epidermis ...
The skin has two layers, the epidermis and the dermis. The epidermis is a stratified squamous epithelium with associated adnexal structures such as hair follicles and sebaceous glands. It is separated from the underlying connective tissue, the dermis, by a basement membrane (red). The three dermal layers are the papillary dermis (PD), reticular dermis (RD), and hypodermis/white adipose tissue. The dermal papilla and arrector pili muscle constitute two specialized populations of dermal mesenchymal cells. Adapted with permission from Science (143).
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