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J Invest Dermatol. 2018 Jun;138(6):1409-1419. doi: 10.1016/j.jid.2017.12.030. Epub 2018 Jan 6.

Wound Regeneration Deficit in Rats Correlates with Low Morphogenetic Potential and Distinct Transcriptome Profile of Epidermis.

Author information

1
Department of Developmental and Cell Biology, University of California, Irvine, Irvine, California, USA; Sue and Bill Gross Stem Cell Research Center, University of California, Irvine, Irvine, California, USA; Center for Complex Biological Systems, University of California, Irvine, Irvine, California, USA.
2
Department of Medical Biology and Genetics, Grodna State Medical University, Grodna, Belarus.
3
Department of Developmental and Cell Biology, University of California, Irvine, Irvine, California, USA; Center for Complex Biological Systems, University of California, Irvine, Irvine, California, USA.
4
Department of Developmental and Cell Biology, University of California, Irvine, Irvine, California, USA; Sue and Bill Gross Stem Cell Research Center, University of California, Irvine, Irvine, California, USA.
5
The Ronald O. Perelman Department of Dermatology, Department of Cell Biology, New York University School of Medicine, New York, New York, USA.
6
Department of Developmental and Cell Biology, University of California, Irvine, Irvine, California, USA; Sue and Bill Gross Stem Cell Research Center, University of California, Irvine, Irvine, California, USA; Department of Anatomy, School of Medicine, Kyungpook National University, Daegu, Republic of Korea; Biomedical Research Institute, Kyungpook National University Hospital, Daegu, Republic of Korea; Hair Transplantation Center, Kyungpook National University Hospital, Daegu, Republic of Korea.
7
Department of Biology, Sonoma State University, Rohnert Park, California, USA.
8
Department of Developmental and Cell Biology, University of California, Irvine, Irvine, California, USA; Sue and Bill Gross Stem Cell Research Center, University of California, Irvine, Irvine, California, USA; Center for Complex Biological Systems, University of California, Irvine, Irvine, California, USA. Electronic address: plikus@uci.edu.

Abstract

Large excisional wounds in mice prominently regenerate new hair follicles (HFs) and fat, yet humans are deficient for this regenerative behavior. Currently, wound-induced regeneration remains a clinically desirable, but only partially understood phenomenon. We show that large excisional wounds in rats across seven strains fail to regenerate new HFs. We compared wound transcriptomes between mice and rats at the time of scab detachment, which coincides with the onset of HF regeneration in mice. In both species, wound dermis and epidermis share core dermal and epidermal transcriptional programs, respectively, yet prominent interspecies differences exist. Compared with mice, rat epidermis expresses distinct transcriptional and epigenetic factors, markers of epidermal repair, hyperplasia, and inflammation, and lower levels of WNT signaling effectors and regulators. When recombined on the surface of excisional wounds with vibrissa dermal papillae, partial-thickness skin grafts containing distal pelage HF segments, but not interfollicular epidermis, readily regenerated new vibrissa-like HFs. Together, our findings establish rats as a nonregenerating rodent model for excisional wound healing and suggest that low epidermal competence and associated transcriptional profile may contribute to its regenerative deficiency. Future comparison between rat and mouse may lend further insight into the mechanism of wounding-induced regeneration and causes for its deficit.

PMID:
29317265
PMCID:
PMC6059613
[Available on 2019-06-01]
DOI:
10.1016/j.jid.2017.12.030

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