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Transcriptional profiling of hair follicle stem cells in the presence and absence of Regulatory T-cells

ABSTRACT: Purpose: The goals of this study were to identify Pathways that Tregs utilize in the skin to maintain tissue homesostasis in the context of hair follcile cycling. Methods: Hair follicle stem cells (HFSCs), in the presence and absence of Tregs, were induced into cycle through a model of depilation induced anagen. HFSCs were then purified by cell sorting at day 4 post depilation based on cell surface marker expression (CD45 negative, MHC Class II negative, Sca-1 negative, EpCAM negative, CD34 Positive, Integrin alpha6 High) to generate mRNA transcription profiles. Results: Transcriptional profiling revealed a significant reduction in proliferation/differentiation associated genes expressed in HFSCs isolated from Treg depleted mice Conclusion: Our study represents the first detailed analysis of Treg modulation of tissue stem cell behaviour

ORGANISM(S): Mus musculus

PROVIDER: GSE76102 | GEO | 2017/04/28

SECONDARY ACCESSION(S): PRJNA306229

REPOSITORIES: GEO

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Project description:Hair follicles undergo recurrent cycling of controlled growth (anagen), regression (catagen), and relative quiescence (telogen) with a defined periodicity. Taking a genomics approach to study gene expression during synchronized mouse hair follicle cycling, we discovered that, in addition to circadian fluctuation, CLOCK-regulated genes are also modulated in phase with the hair growth cycle. During telogen and early anagen, circadian clock genes are prominently expressed in the secondary hair germ, which contains precursor cells for the growing follicle. Analysis of Clock and Bmal1 mutant mice reveals a delay in anagen progression, and the secondary hair germ cells show decreased levels of phosphorylated Rb and lack mitotic cells, suggesting that circadian clock genes regulate anagen progression via their effect on the cell cycle. Consistent with a block at the G1 phase of the cell cycle, we show a significant upregulation of p21 in Bmal1 mutant skin. While circadian clock mechanisms have been implicated in a variety of diurnal biological processes, our findings indicate that circadian clock genes may be utilized to modulate the progression of non-diurnal cyclic processes. To investigate the molecular control of hair follicle cycling, we profiled mRNA expression in mouse dorsal skin at multiple representative time points in the synchronized second postnatal hair growth cycle and in a depilation-induced hair growth cycle. For profiling of second synchronized and depilation-induced hair growth cycle, the same upper-mid region of dorsal skin was excised from C57BL/6 mice at representative postnatal days (P). The time points for second hair growth cycle are classified into different phases of the hair growth cycle based on established morphological guidelines as follow: early anagen (P23, P25), mid anagen (P27), late anagen (P29, P34), early catagen (P37, P39), mid catagen (P41), and telogen (P44). Depilation-induced hair growth cycle by applying wax/rosin mixture on the dorsal skin of seven-week old mice (all follicles in telogen) was performed on mice. The corresponding phases of the hair growth cycle at number of days following depilation (D) is as follow: early anagen (D3), mid anagen (D5), late anagen (D8, D12), and early catagen (D17). For each time point, multiple biological replicates were profiled, with each mouse dorsal skin separately hybridized to an Affymetrix array.

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Transcriptional profiling of hair follicle stem cells in the presence and absence of Regulatory T-cells

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