Unknown,Transcriptomics,Genomics,Proteomics

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Fgf18 regulates hair cycle

ABSTRACT: Fgf18 gene is strongly expressed in hair follicles of mouse dorsal skin during regressing (catagen) and resting (telogen) phases of hair cycle, but not in growth (anagen) phase. This study aims at identifying the function of Fgf18 in the regulation of hair cycle. To define target genes of Fgf18 during telogen phase of hair cycle, we generated mice in which Fgf18 gene is conditionally knocked out in keratin 5-positive epithelial cells (referred to as Fgf18 cKO below). We carried out microarray experiments with mouse back skin samples harboring telogen hair follicles obtained from three 42-d-old Fgf18 cKO male mice, or from three 42-d-old C57BL/6 male mice as control. Total RNA was isolated from each mouse and further purified to polyA RNA using oligo dT30 columns. The RNA samples were pooled for each group. Gene expression was analyzed by one-color analysis using duplicate arrays for each group.

ORGANISM(S): Mus musculus

SUBMITTER: Myco Umemura

PROVIDER: E-GEOD-29547 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Project description:Inner Mongolia Cashmere Goat is a local excellent breed of cashmere and meat dual-purpose, which is a typical heterogeneous indumentum. The hair follicles cycle through periods of vigorous growth (anagen), a regression caused by apoptosis (catagen), and relative rest (telogen). At present, it is not clear which genes affect the cycle transformation of hair follicles and unclear how proteins impact the creation and expansion of hair follicles. In this work, we investigated the possible pathways of transformation and apoptosis in goat hair follicles using multi-omics joint analysis methodologies. The results showed that 917 , 1187 and 716 proteins were specifically expressed in anagen, catagen and telogen. The result of gene ontology (GO) annotation showed that differentially expressed proteins（DEPs) are in different growth cycle periods, and enriched GO items are mostly related to the transformation of cells and proteins. The Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment result indicated that the apoptosis process has a great impact on hair follicle's growth cycle. The results of the protein interaction network of differential proteins showed that the Ribosomal Protein family ( RPL4, RPL8, RPS16, RPS18, RPS2, RPS27A, RPS3 ) was the core protein in the network. The results of combined transcriptome and proteomics analysis showed that there were 16,34, and 26 overlapped DEGs and DEPs in the comparison of anagen VS catagen, catagen VS telogen and anagen VS telogen, of which API5 plays an important role in regulating protein and gene expression levels. We focused on API5 and Ribosomal protein and found that API5 affected the apoptosis process of hair follicles, and Ribosomal Protein was highly expressed in the resting stage of hair follicles. They are both useful as molecular marker candidate genes to study hair follicle growth and apoptosis, and they both have an essential function in the cycle transition process of hair follicles. The results of this study may provide a theoretical basis for further research on the growth and development of hair follicles in Inner Mongolian Cashmere goats.

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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Fgf18 regulates hair cycle

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