The core mission of the Driskell Laboratory is to investigate mechanisms that will induce regeneration in skin wounds utilizing fibroblast lineages.
The Story of Scar Formation in Skin and a Way to Achieve Scar-less Wound Repair
Picture:Young skin heals with minimal scarring. This is because young skin has the ability to regenerate hair follicles in the wounds (red arrows in the picture). Understanding how to reverse the effects of aging in older skin will lead to better skin repair.
The story of scar formation in the skin starts with an infliction of a wound, which is essentially a newly created hole in the tissue that becomes filled with many different cell types. This includes migrating blood, mesenchymal cells (fibroblasts), epithelial cells which interact to form new tissue which rebuilds new tissue within the hole. The spatial and temporal interactions during this process is critical for repairing the tissue, which normally results in the formation of a scar. Interestingly, it is possible to modulate the repair process, thereby influencing the quality of repair, by controlling epithelial cells and fibroblasts as they enter the blood clot.
We have recently discovered that, by controlling the nature of a fibroblasts before and after wounding in the skin, we can influence hair regeneration in the wound, which represents an essential part of skin regeneration (Driskell e al. 2013 – Nature). In addition, we found that the reason why scars normally lack hair is because adult skin lacks fibroblast subtypes that support hair follicle development. Furthermore, we have also found why young skin heals better than older skin. This is because the critical cells required for hair follicle neogenesis can be found in normal young (neonatal) dermis of mice or can be induced to replicate by increasing Wnt signalling in the epidermis before wounding (Driskell et al. 2013; Rognoni et al. 2016). Despite these advances, our findings revealed a need to investigate the mechanisms that control the type of hair follicle regeneration in the wound and its ability to function.
- Salz L, and Driskell RR. (2017) The Sox2: GFP+/- knock in mouse model does not faithfully recapitulate Sox2 expression in skin. Exp Dermatol. doi: 10.1111/exd.13396. PMID: PMCID:
- Salz L, and Driskell RR. (2017) A novel processing and imaging protocol for thick three-dimensional cross-sections of skin called “Horizontal Whole Mount”. Journal of Visualized Experiments In Press PMID: PMCID:
- Mastrogiannaki M, Lichtenberger BM, Reimer A, Collins CA, Driskell RR, and Watt FM. (2016) b-catenin stabilization in skin fibroblasts causes fibrotic lesions by preventing adipocyte differentiation of the reticular dermis. J. Invest. Dermatol. 136(6):1130-42. doi: 10.1016/j.jid2016.01.036. PMID: PMCID:
- Rognoni E, Gomez, Pisco AO, Rawlins EL, Watt FM, and Driskell RR. (2016) Inhibition of b-catenin signaling in dermal fibroblasts enhances hair follicle regeneration during wound healing. Development 143:2522-2535; doi 10.1242/dev.131797. PMID: PMCID:
- Kretzschmar K, Weber C, Driskell RR, Calonje E, Watt FM. (2016) Compartmentalized epidermal activation of beta-catenin differentially affects lineage reprogramming and underlies tumor heterogeneity. Cell Rep. 12;14(2):269-81 PMID: PMCID:
- Driskell RR, Watt FM. (2015) Understanding fibroblast heterogeneity in the skin. Trends Cell Biol. 25(2): 92-9. PMID: PMCID:
- Kaushal G, Rognoni E, Lichtenberger BM, Driskell RR, Kretzschmar K, Hoste E, and Watt FM. (2015) Fate of Prominin-1 expressing dermal papilla cells during homeostasis, wound healing and Wnt activation. J. Invest. Dermatol. 135(12):2926-34. Doi: 10.1038/jid.2015.319 PMID: PMCID:
- Driskell RR, Jahoda CA, Chuong CM, Watt FM, and Horsley V. (2014) Defining dermal adipose tissue. Exp Dermatol. 23(9):629-31. doi: 10.1111/exd.12450. PMID: PMCID:
- Driskell RR, Lichtenberger BM, Hoste E, Kretzschmar K, Simons B, Charalambous M, Ferron SR, Herault G, Pavlovic G, Ferguson-Smith AC, and Watt FM. (2013) Distinct fibroblast lineages determine dermal architecture during skin development and repair. Nature. 12;504(7479):277-81. doi: 10.1038/nature12783. PMID: PMCID:
- Lesko M*, Driskell RR*, Kretzschmar K, Goldie S, Watt FM. (2013) Sox2 modulates the function of two distinct cell lineages in mouse skin. Dev Biol. 1;382(1):15-26. doi: 10.1016/j.ydbio.2013.08.004. Epub 2013 Aug 13. PMID: PMCID:
- Driskell RR*, Juneja VR*, Connelly JT, Kretzschmar K, Tan DW, Watt FM. (2011) Clonal growth of dermal papilla cells reveals intrinsic differences between Sox2-Positive and –Negative cells in vitro and in vivo. J. Invest. Dermatol. Doi:10.1038/jid2011.428 [Epub ahead of print] PMID: PMCID:
- Arwert EN, Mentink RA, Driskell RR, Hoste E, Goldie SJ, Quist S, Watt FM. (2011) Upregulation of CD26 expression in epithelial cells and stromal cells during wound-induced skin tumor formation. Oncogene. doi: 10.1038/onc.2011.293 [Epub ahead of print] PMID: PMCID:
- Driskell, R.R., Clavel C., Rendl, M., Watt F.M. (2011) Hair follicle dermal papilla cells at a glance. Journal of Cell Science 15; 124 (pt8) 1179-1182. PMID: PMCID:
- *Jensen, K.B. *Driskell, R.R Watt, F.M. (2010) Assaying proliferation and differentiation capacity of stem cells using disaggregated adult mouse epidermis. Nature Protocols. 5 (5): 898-911. PMID: PMCID:
- Watt F.M., Driskell R.R. (2010) The therapeutic potential of stem cells. Phil Trans Royal Society 365:1537 pg155-163 PMID: PMCID:
- Driskell, R.R., Giangreco, A., Jensen, K.B., Mulder, K.W., and Watt, F.M. (2009) Sox2-positive dermal papilla cells specify hair follicle type in mammalian epidermis. Development 136 (16): 2815-23. PMID: PMCID:
- Driskell, R.R. Goodheart, M. Neff, T., Liu, X., Moothart C.M., and Engelhardt, J.F. (2007) Wnt3a Regulates Lef-1 Expression During Airway Submucosal Gland Morphogenesis. Dev Bio. 1:305(3): 90-102 PMID: PMCID:
- Liu, X., Driskell, R.R. and Engelhardt J.F. (2006) Stem cells in the lung. Methods Enzymol. 419;285-321. PMID: PMCID:
- Liu, X., Driskell, R.R., Luo, M., Abbot, D., Filali, M., Cheng, N., Sigmund, C.D., and Engelhardt, J.F. (2004) Characterization of Lef-1 Promoter Segments that Facilitate Inductive Developmental Expression in Skin. J. Invest. Dermatol. 123(2):264-74. PMID: PMCID:
- Driskell, R.R., Liu, X., Luo, M., Filali, M., Abbott, D., Cheng, N., Moothart, C., Sigmund, C.D., and Engelhardt, J.F. (2004) Wnt-Responsive Element Controls Lef-1 Promoter Expression During Submucosal Gland Morphogenesis. American Journal of Physiology-LCMP. Am. J. Physiol. Lung Cell Mol. Physiol. 287:L752-63. PMID: PMCID:
- Liu, X., Driskell, R.R. and Engelhardt, J.F. (2004) Airway Glandular Development and Stem Cells. Current Topics in Developmental Biology Vol. 6, Elsevier, Inc. 64:33-56 PMID: PMCID:
- Driskell, R.R., and Engelhardt, J.F. (2004) Stem Cells in the Adult Lung. Handbook of Stem Cells PMID: PMCID:
- Liu, X., Yan, Z., Luo, M., Zak, R., Li, Z., Driskell, R.R., Huang, Y., Tran, N., and Engelhardt, J.F. (2004) Targeted correction of single-base-pair mutations with adeno-associated virus vectors under nonselective conditions. J. Virol. 78:4165-75. PMID: PMCID:
- Driskell, R.A., and Engelhardt, J.F. (2003) Current status of gene therapy for inherited lung diseases. Annu. Rev. Physiol. 65:585-612. PMID: PMCID: