Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

Transcription profiling of mouse skin after acute withdrawal of TERT

ABSTRACT: TERT is an essential protein component of telomerase, a ribonuclearprotein complex that protects chromosomal ends. Ectopic expression of TERT in mouse skin activates hair follicle stem cells and induces active growth phase of hair cycles, called anagen. This activity of TERT is independent of its reverse transcriptase function, indicating that this is a non-telomeric function of TERT. We performed time-course microarray analysis using conditional bi-transgenic mice (iK5-TERT) to understand the mechanism of this novel non-telomeric function of TERT. Experiment Overall Design: Hair follicles of iK5-TERT mice at postnatal day 60 is in TERT-induced anagen. To those mice, we injected either PBS, to maintain TERT transgene expression, or doxycycline, to rapidly extinguish transgene expression. We then took time-course dorsal skin biopsies (0,6,12,24 hr) of these mice and analyzed differential gene expressions using Affymetrix Genechips and various bioinformatic tools, including SAM, to discover TERT-regulated genes.

ORGANISM(S): Mus musculus

SUBMITTER: Jinkuk Choi

PROVIDER: E-GEOD-9725 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

TERT promotes epithelial proliferation through transcriptional control of a Myc- and Wnt-related developmental program.

Choi Jinkuk J Southworth Lucinda K LK Sarin Kavita Y KY Venteicher Andrew S AS Ma Wenxiu W Chang Woody W Cheung Peggie P Jun Sohee S Artandi Maja K MK Shah Naman N Kim Stuart K SK Artandi Steven E SE

PLoS genetics 20071213 1

Telomerase serves a critical role in stem cell function and tissue homeostasis. This role depends on its ability to synthesize telomere repeats in a manner dependent on the reverse transcriptase (RT) function of its protein component telomerase RT (TERT), as well as on a novel pathway whose mechanism is poorly understood. Here, we use a TERT mutant lacking RT function (TERT(ci)) to study the mechanism of TERT action in mammalian skin, an ideal tissue for studying progenitor cell biology. We show ...[more]

PMID: 18208333

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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.

Dataset Information

Transcription profiling of mouse skin after acute withdrawal of TERT

Publications

TERT promotes epithelial proliferation through transcriptional control of a Myc- and Wnt-related developmental program.

Similar Datasets

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