Distinct fibroblast lineages determine dermal architecture in skin development and repair

By R. Driskell, B. Lichtenberger, E. Hoste, Kai Kretzschmar, Benjamin D. Simons, M. Charalambous, S. Ferrón, Y. Hérault, G. Pavlovic, Anne Ferguson-Smith and 1 more. Nature, 2013

1,112 citations recorded by the source corpus.

Fibroblasts are the major mesenchymal cell type in connective tissue and deposit the collagen and elastic fibres of the extracellular matrix (ECM). 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 β-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. They also form a platform for discovering fibroblast lineages in other tissues and for examining fibroblast changes in ageing and disease.

Subfields: Molecular Biology, Rehabilitation, Urology

View Paper: https://www.semanticscholar.org/paper/2877288874d179727baa5532b488ef2474123aab

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Molecular Biology

1. M. Tomic‐Canic
2. Paul Martin
3. Qingxiang Zeng
4. G. Gurtner
5. Junjiang Liu
6. Jin Yang
7. J. Mu
8. Shuzhi Deng

In Rehabilitation

1. Paul Martin
2. S. Eming
3. M. Tomic‐Canic
4. Nadia A. Rosenthal
5. J. Biernaskie
6. V. Horsley

In Urology

1. Paul Martin
2. V. Horsley

Citations in the corpus

• Cellular and molecular mechanisms of skin wound healing (2024, positive): “Although mouse skin is very different from human skin, many recent insights about what might be driving scarring have been derived from mouse studies and some of these insights may be indicative of the underlying mechanisms in human skin following wounding 124,125 .”
• The molecular anatomy of mouse skin during hair growth and rest (2019, background): “Although a variety of fibroblast subtypes have been defined in embryonic and adult skin, the full extent of fibroblast heterogeneity in the skin is not resolved (Driskell et al., 2013; Korosec et al., 2019; Philippeos et al., 2018; Rinkevich et al., 2015, Tabib et al., 2018).”
• Fibroblasts: origins, definitions, and functions in health and disease (2021, background): “As skin morphogenesis completes in early postnatal time and adult homeostasis ensues, fibroblasts undergo maturation and change their marker expression patterns (Driskell et al., 2013; Rognoni et al., 2016).”
• Wound Healing: A Cellular Perspective. (2019, methodology): “Lineage tracing studies have revealed that initial dermal repair is attributed to the lower lineage fibroblasts that express myofibroblast markers such as -SMA (92).”
• Wound healing: cellular mechanisms and pathological outcomes (2020, background): “[66] demonstrated that skin fibroblasts originate from two distinct lineages, where the upper lineage aids re-epithelialization while the lower lineage contributes to ECM deposition.”
• Signaling pathways in cancer-associated fibroblasts and targeted therapy for cancer (2021, background): “Recently, single-cell RNA-sequencing and conventional RNA-sequencing of human tissues have allowed better unbiased assessment of heterogeneous CAFs.(20,58,59) By analyzing a combination of classical markers, such as FAP and PDGFRβ, CAFs in breast cancer were distinguished by levels of marker express”
• Wound healing and skin regeneration. (2015, background): “This study illustrates the importance of the dermal contribution to not only wound healing, but also to appendage regeneration (Driskell et al. 2013).”
• Wound repair and regeneration: Mechanisms, signaling, and translation (2014, positive): “For cell therapy, timing may also be important, as a recent study in mice showed that two populations of stem cells exist in the wound: one superficially, critical for hair development, and one deeper, forming the lower dermis, and possibly an early source of locally derived wound fibroblasts (98).”