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The cycling hair follicle as an ideal systems biology research model.

ABSTRACT: In the postgenomic era, systems biology has rapidly emerged as an exciting field predicted to enhance the molecular understanding of complex biological systems by the use of quantitative experimental and mathematical approaches. Systems biology studies how the components of a biological system (e.g. genes, transcripts, proteins, metabolites) interact to bring about defined biological function or dysfunction. Living systems may be divided into five dimensions of complexity: (i) molecular; (ii) structural; (iii) temporal; (iv) abstraction and emergence; and (v) algorithmic. Understanding the details of these dimensions in living systems is the challenge that systems biology aims to address. Here, we argue that the hair follicle (HF), one of the signature features of mammals, is a perfect and clinically relevant model for systems biology research. The HF represents a stem cell-rich, essentially autonomous mini-organ, whose cyclic transformations follow a hypothetical intrafollicular "hair cycle clock" (HCC). This prototypic neuroectodermal-mesodermal interaction system, at the cross-roads of systems and chronobiology, encompasses various levels of complexity as it is subject to both intrafollicular and extrafollicular inputs (e.g. intracutaneous timing mechanisms with neural and systemic stimuli). Exploring how the cycling HF addresses the five dimensions of living systems, we argue that a systems biology approach to the study of hair growth and cycling, in man and mice, has great translational medicine potential. Namely, the easily accessible human HF invites preclinical and clinical testing of novel hypotheses generated with this approach.

SUBMITTER: Al-Nuaimi Y

PROVIDER: S-EPMC4383261 | biostudies-literature | 2010 Aug

REPOSITORIES: biostudies-literature

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The cycling hair follicle as an ideal systems biology research model.

Al-Nuaimi Yusur Y Baier Gerold G Watson Rachel E B RE Chuong Cheng-Ming CM Paus Ralf R

Experimental dermatology 20100801 8

In the postgenomic era, systems biology has rapidly emerged as an exciting field predicted to enhance the molecular understanding of complex biological systems by the use of quantitative experimental and mathematical approaches. Systems biology studies how the components of a biological system (e.g. genes, transcripts, proteins, metabolites) interact to bring about defined biological function or dysfunction. Living systems may be divided into five dimensions of complexity: (i) molecular; (ii) st ...[more]

PMID: 20590819

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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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The cycling hair follicle as an ideal systems biology research model.

Publications

The cycling hair follicle as an ideal systems biology research model.

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