Gene Expression in Rat Dermal Papilla Cells: Analysis of 2529 ESTs

Sleeman, Matthew A.; Murison, J. Greg; Strachan, Lorna; Kumble, Krishnanand D.; Glenn, M.; McGrath, Annette; Grierson, A.W.; Havukkala, Ilkka; Tan, Paul; Watson, James D.

doi:10.1006/geno.2000.6300

Cited by 13 publications

(18 citation statements)

References 43 publications

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“…Importantly, 38 of these genes are reportedly overrepresented in mouse DP cells (Fig. 2C) (Sleeman et al, 2000;Botchkarev and Kishimoto, 2003;Panteleyev et al, 2003;O'Shaughnessy et al, 2004;Rendl et al, 2005;Driskell et al, 2009). Most of them were established DP signature genes (Botchkarev and Kishimoto, 2003;Rendl et al, 2005;Ito et al, 2007;Osada et al, 2007;Driskell et al, 2009;Ohyama et al, 2010), including those encoding key molecules that enhance [e.g.…”

Section: Resultsmentioning

confidence: 94%

Restoration of the intrinsic properties of human dermal papilla in vitro

Ohyama

Kobayashi

Sasaki

et al. 2012

Journal of Cell Science

129

189

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SummaryThe dermal papilla (DP) plays pivotal roles in hair follicle morphogenesis and cycling. However, characterization and/or propagation of human DPs have been unsatisfactory because of the lack of efficient isolation methods and the loss of innate characteristics in vitro. We hypothesized that culture conditions sustaining the intrinsic molecular signature of the human DP could facilitate expansion of functional DP cells. To test this, we first characterized the global gene expression profile of microdissected, non-cultured human DPs. We performed a 'two-step' microarray analysis to exclude the influence of unwanted contaminants in isolated DPs and successfully identified 118 human DP signature genes, including 38 genes listed in the mouse DP signature. The bioinformatics analysis of the DP gene list revealed that WNT, BMP and FGF signaling pathways were upregulated in intact DPs and addition of 6-bromoindirubin-39-oxime, recombinant BMP2 and basic FGF to stimulate these respective signaling pathways resulted in maintained expression of in situ DP signature genes in primarily cultured human DP cells. More importantly, the exposure to these stimulants restored normally reduced DP biomarker expression in conventionally cultured DP cells. Cell growth was moderate in the newly developed culture medium. However, rapid DP cell expansion by conventional culture followed by the restoration by defined activators provided a sufficient number of DP cells that demonstrated characteristic DP activities in functional assays. The study reported here revealed previously unreported molecular mechanisms contributing to human DP properties and describes a useful technique for the investigation of human DP biology and hair follicle bioengineering.

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Section: Resultsmentioning

confidence: 94%

Restoration of the intrinsic properties of human dermal papilla in vitro

Ohyama

Kobayashi

Sasaki

et al. 2012

Journal of Cell Science

129

189

View full text Add to dashboard Cite

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“…Gene expression changes in cultured DP cells Compared with other gene expression analyses on the DP (Sleeman et al, 2000) many of the same genes were expressed in the DP and cultured DP cells. Although differences between the two analyses were reflected by the fact that there were differences in methodology (EST sequencing vs array hybridization), there were still clear differences in the biology of the in vivo DP and cultured DP cells, even after a single passage.…”

Section: Discussionmentioning

confidence: 94%

“…Recent attempts to characterize gene expression in the DP have relied upon the expansion of cell number by repeated passages in culture (Sleeman et al, 2000). According to the above postulate, many important genes expressed in anagen would not be present in DP cells in culture, and therefore they do not accurately model the in vivo status of the DP in an anagen hair follicle.…”

mentioning

confidence: 99%

The WNT Signalling Modulator, Wise, is Expressed in an Interaction-Dependent Manner During Hair-Follicle Cycling

O'Shaughnessy

Yeo

Gautier

et al. 2004

Journal of Investigative Dermatology

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We used microarray hybridization to identify genes induced in the dermal papilla (DP) during anagen as a result of the interaction with epithelial matrix cells. We identified inhibitors of the bone morphogenetic protein (BMP) and transforming growth factor beta (TGFbeta)-signalling pathway, as well as the rat homologue of the Xenopus-secreted WNT modulator Wise. A large number of genes previously determined to be expressed in the DP were shown to be expressed in both the DP and dermal sheath (DS). Genes induced in the DP during anagen included modulators of genes expressed additionally in the DS as well as specialized extracellular matrix components. Expression of some of these genes were lost when the DP cells were cultured, suggesting that their expression was interaction dependent. One such gene, the WNT-signalling modulator Wise, was expressed in the DP and not in the non-inductive DS and was additionally expressed at high levels in the precortex and in the putative bulge region. In addition to the reported WNT-signalling modulation role, we show that Wise reduced both BMP and TGFbeta signalling in transformed fibroblasts. We speculate that loss of gene expression in cultured cells is a model for the loss of gene expression observed at catagen.

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“…Because the DP resides in the center of a diverse cellular niche, comprised of surrounding Mx and ORS cells, Mc, and dermal sheath cells, its relative inaccessibility, coupled with its loss of potential in vitro, have posed major technical hurdles in cleanly isolating populations of these cells. Thus, although microarray and cDNA library analyses have been conducted on microdissected and/or cultured whisker DP [10–12], the array data have yielded only a handful of the known DP markers, making it difficult to evaluate the potential significance of unexpectedly expressed genes from these arrays.…”

Section: Introductionmentioning

confidence: 99%

Molecular Dissection of Mesenchymal–Epithelial Interactions in the Hair Follicle

2005

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De novo hair follicle formation in embryonic skin and new hair growth in adult skin are initiated when specialized mesenchymal dermal papilla (DP) cells send cues to multipotent epithelial stem cells. Subsequently, DP cells are enveloped by epithelial stem cell progeny and other cell types to form a niche orchestrating hair growth. Understanding the general biological principles that govern the mesenchymal–epithelial interactions within the DP niche, however, has been hampered so far by the lack of systematic approaches to dissect the complete molecular make-up of this complex tissue. Here, we take a novel multicolor labeling approach, using cell type–specific transgenic expression of red and green fluorescent proteins in combination with immunolabeling of specific antigens, to isolate pure populations of DP and four of its surrounding cell types: dermal fibroblasts, melanocytes, and two different populations of epithelial progenitors (matrix and outer root sheath cells). By defining their transcriptional profiles, we develop molecular signatures characteristic for the DP and its niche. Validating the functional importance of these signatures is a group of genes linked to hair disorders that have been largely unexplored. Additionally, the DP signature reveals novel signaling and transcription regulators that distinguish them from other cell types. The mesenchymal–epithelial signatures include key factors previously implicated in ectodermal-neural fate determination, as well as a myriad of regulators of bone morphogenetic protein signaling. These findings establish a foundation for future functional analyses of the roles of these genes in hair development. Overall, our strategy illustrates how knowledge of the genes uniquely expressed by each cell type residing in a complex niche can reveal important new insights into the biology of the tissue and its associated disease states.

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Gene Expression in Rat Dermal Papilla Cells: Analysis of 2529 ESTs

Cited by 13 publications

References 43 publications

Restoration of the intrinsic properties of human dermal papilla in vitro

Restoration of the intrinsic properties of human dermal papilla in vitro

The WNT Signalling Modulator, Wise, is Expressed in an Interaction-Dependent Manner During Hair-Follicle Cycling

Molecular Dissection of Mesenchymal–Epithelial Interactions in the Hair Follicle

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