Gene Expression Architecture of Mouse Dorsal and Tail Skin Reveals Functional Differences in Inflammation and Cancer

Quigley, David A.; Kandyba, Eve; Huang, Pamela; Halliwill, Kyle; Sjölund, Jonas; Pelorosso, Facundo Germán; Wong, Cynthia M.; Hirst, Gillian L.; Wu, Di; Delrosario, Reyno; Kumar, Atul; Balmain, Allan

doi:10.1016/j.celrep.2016.06.061

Cited by 21 publications

(25 citation statements)

References 81 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…To confirm these shifts in K79 expression, we generated mice in which a lacZ cassette, encoding β-galactosidase (β-gal), was inserted into the endogenous K79 locus, thereby inactivating the allele but also serving as a reporter for K79 promoter activity ( K79 tm2a mice) (Figure 2H). K79 tm2a/+ mice did not display any overt abnormalities, while β-gal activity recapitulated the expression pattern for K79 in the skin (Quigley et al, 2016; Veniaminova et al, 2013). This included strong activity in columns extending out from hair germs; in the sebaceous glands and suprabasal cells of the infundibulum in adult follicles; and in the early CL (Figure 2I–J).…”

Section: Resultsmentioning

confidence: 67%

Hair Follicle Terminal Differentiation Is Orchestrated by Distinct Early and Late Matrix Progenitors

et al. 2017

View full text Add to dashboard Cite

SUMMARY During development and regeneration, matrix progenitors undergo terminal differentiation to form the concentric layers of the hair follicle. These differentiation events are thought to require signals from the mesenchymal dermal papilla (DP); however, it remains unclear how DP-progenitor cell interactions govern specific cell fate decisions. Here, we show that the hair follicle differentiated layers are specified asynchronously, with early matrix progenitors initiating differentiation prior to surrounding the DP. Furthermore, these early matrix cells can undergo terminal differentiation in the absence of Shh, BMP signaling, and DP maturation. Whereas early matrix progenitors form the hair follicle companion layer, later matrix populations progressively form the inner root sheath and hair shaft. Together, our findings characterize some of the earliest terminal differentiation events in the hair follicle, and reveal that the matrix progenitor pool can be divided into early and late phases based on distinct temporal, molecular and functional characteristics.

show abstract

Section: Resultsmentioning

confidence: 67%

Hair Follicle Terminal Differentiation Is Orchestrated by Distinct Early and Late Matrix Progenitors

et al. 2017

View full text Add to dashboard Cite

show abstract

“…Given that this is a systemically‐induced disease model, it should be expected that all skin areas would be affected; however, differences in magnitude and kinetics were evident. Contributing to the observed differences may be that skin properties including thickness, cell architecture, protective properties of hair/fur and sensitivity to inflammation are not uniform throughout the body . Based on the observed differences in disease severity across skin sites, we focused on the ear as the primary readout.…”

Section: Discussionmentioning

confidence: 99%

“…Contributing to the observed differences may be that skin properties including thickness, cell architecture, protective properties of hair/fur and sensitivity to inflammation are not uniform throughout the body. [32][33][34] Based on the observed differences in disease severity across skin sites, we focused on the ear as the primary readout.…”

Section: Discussionmentioning

confidence: 99%

Characterization of psoriasiform dermatitis induced by systemic injection of interleukin‐23 minicircles in mice

Leys

Wang

Paulsboe

et al. 2019

The Journal of Dermatology

View full text Add to dashboard Cite

The interleukin (IL)‐23/IL‐17 axis plays a central role in the pathogenesis of psoriasis and is elevated in lesional psoriatic skin. Different murine models have been developed to mimic this pathophysiology each carrying specific merits and limitations. In an attempt to address some of these limitations, B10.RIII mice received a single hydrodynamic injection of IL‐23 minicircles (MC) to induce hepatic transcription and the endogenous production of IL‐23. Plasma and ear IL‐23 levels were dose‐dependently (0.3–3 μg) increased in MC injected mice and were sustained over the 14‐day study duration. Beginning on day 7 post‐injection, mice developed dose‐related ear inflammation, histologically confirmed increases in epidermal and dermal area, as well as enhanced neutrophil and macrophage content. Flow cytometry demonstrated increased levels of granulocytes, T cells and monocytes/macrophages in the ear skin, with T cells identified as the main cellular source of IL‐17A. Evaluation of mRNA and protein showed time‐dependent, increased levels of the IL‐23/IL‐17 pathway and inflammatory/microbial cytokines/chemokines in the ear which differed kinetically from circulating levels. An anti‐IL‐23p40 antibody was assessed following both prophylactic administration and administration once the disease was established. Prophylactic dosing completely prevented the development of the ear phenotype across endpoints. Treatment administration showed a dose‐related response, with a maximum inhibition of 64–94%, depending on endpoint. These data demonstrate that the IL‐23 MC model is a useful approach to study IL‐23/IL‐17‐driven skin inflammation and may facilitate preclinical assessment of novel therapies.

show abstract

“…The location of SCCs in Mastomys coucha also contrasts with the MmuPV1 mouse system where lesions preferentially develop at the tail, muzzle or ear, while the back skin was less predisposed or even resistant [ 19 , 72 ]. The putative underlying reason was recently addressed in an elegant study using quantitative trait loci network analysis in mice [ 78 ]. According to this report, dorsal and tail skin is not only dissimilar by different keratin networks and transcription factors, but also due to their lower expression of markers for tissue-resident Langerhans cells and MHC expression.…”

Section: Discussionmentioning

confidence: 99%

The interplay of UV and cutaneous papillomavirus infection in skin cancer development

et al. 2017

View full text Add to dashboard Cite

Cutaneous human papillomaviruses (HPVs) are considered as cofactors for non-melanoma skin cancer (NMSC) development, especially in association with UVB. Extensively studied transgenic mouse models failed to mimic all aspects of virus-host interactions starting from primary infection to the appearance of a tumor. Using the natural model Mastomys coucha, which reflects the human situation in many aspects, we provide the first evidence that only UVB and Mastomys natalensis papillomavirus (MnPV) infection strongly promote NMSC formation. Using UVB exposures that correspond to UV indices of different geographical regions, irradiated animals developed either well-differentiated keratinizing squamous cell carcinomas (SCCs), still supporting productive infections with high viral loads and transcriptional activity, or poorly differentiated non-keratinizing SCCs almost lacking MnPV DNA and in turn, early and late viral transcription. Intriguingly, animals with the latter phenotype, however, still showed strong seropositivity, clearly verifying a preceding MnPV infection. Of note, the mere presence of MnPV could induce γH2AX foci, indicating that viral infection without prior UVB exposure can already perturb genome stability of the host cell. Moreover, as shown both under in vitro and in vivo conditions, MnPV E6/E7 expression also attenuates the excision repair of cyclobutane pyrimidine dimers upon UVB irradiation, suggesting a viral impact on the DNA damage response. While mutations of Ras family members (e.g. Hras, Kras, and Nras) were absent, the majority of SCCs harbored—like in humans—Trp53 mutations especially at two hot-spots in the DNA-binding domain, resulting in a loss of function that favored tumor dedifferentiation, counter-selective for viral maintenance. Such a constellation provides a reasonable explanation for making continuous viral presence dispensable during skin carcinogenesis as observed in patients with NMSC.

show abstract

Gene Expression Architecture of Mouse Dorsal and Tail Skin Reveals Functional Differences in Inflammation and Cancer

Cited by 21 publications

References 81 publications

Hair Follicle Terminal Differentiation Is Orchestrated by Distinct Early and Late Matrix Progenitors

Hair Follicle Terminal Differentiation Is Orchestrated by Distinct Early and Late Matrix Progenitors

Characterization of psoriasiform dermatitis induced by systemic injection of interleukin‐23 minicircles in mice

The interplay of UV and cutaneous papillomavirus infection in skin cancer development

Contact Info

Product

Resources

About