The Post-Apoptotic Fate of RNAs Identified Through High-Throughput Sequencing of Human Hair

Stem Cell Program, Division of Dermatology, Department of Medicine, Institute for Genomic Medicine, University of California San Diego, San Diego, California, United States of America.
PLoS ONE (Impact Factor: 3.53). 11/2011; 6(11):e27603. DOI: 10.1371/journal.pone.0027603
Source: PubMed

ABSTRACT The hair of all mammals consists of terminally differentiated cells that undergo a specialized form of apoptosis called cornification. While DNA is destroyed during cornification, the extent to which RNA is lost is unknown. Here we find that multiple types of RNA are incompletely degraded after hair shaft formation in both mouse and human. Notably, mRNAs and short regulatory microRNAs (miRNAs) are stable in the hair as far as 10 cm from the scalp. To better characterize the post-apoptotic RNAs that escape degradation in the hair, we performed sequencing (RNA-seq) on RNA isolated from hair shafts pooled from several individuals. This hair shaft RNA library, which encompasses different hair types, genders, and populations, revealed 7,193 mRNAs, 449 miRNAs and thousands of unannotated transcripts that remain in the post-apoptotic hair. A comparison of the hair shaft RNA library to that of viable keratinocytes revealed surprisingly similar patterns of gene coverage and indicates that degradation of RNA is highly inefficient during apoptosis of hair lineages. The generation of a hair shaft RNA library could be used as months of accumulated transcriptional history useful for retrospective detection of disease, drug response and environmental exposure.

  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: In the present study, we evaluated the possibility that we can utilize hair shaft miR-29a levels as disease marker of scleroderma. Hair samples were obtained from 20 scleroderma patients, 5 dermatomyositis patients and 13 controls. microRNAs were purified from hairs as well as skins or sera, and miR-29a levels were measured with quantitative real-time polymerase chain reaction Mean hair miR-29a levels in scleroderma patients were significantly lower than those in control subjects or dermatomyositis, while expression levels of hair shaft marker keratin 34 were similar among them. There was no strong correlation among the miR-29a levels in the hair, skin and serum of each patient, suggesting that hair microRNAs can be independent biomarkers. We found scleroderma patients with decreased miR-29a levels had contracture of the phalanges at a significantly higher prevalence than those without. To confirm the clinical usefulness of hair microRNAs, large-scale researches are needed in the future. This article is protected by copyright. All rights reserved.
    Experimental Dermatology 09/2013; 22(12). DOI:10.1111/exd.12245 · 4.12 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Objective diagnostic markers have not been in clinical use for psoriasis. In this study, we investigated the levels of miR-424 in hair roots and hair shafts in psoriatic patients, and evaluated the possibility that miR-424 can be a biomarker of the disease. A single hair root and five pieces of hair shafts (~5 cm in length) were obtained from the non-lesional occiput of each individual of 26 psoriatic patients. Control hair samples were collected from nine normal subjects. Samples from 10 atopic dermatitis patients were also included as the disease control. miR-424 levels were determined by quantitative real-time polymerase chain reaction. Hair shaft miR-424 levels were significantly upregulated only in patients with psoriasis compared with normal controls and those with atopic dermatitis. By receiver-operator curve analysis of hair shaft miR-424 to distinguish psoriatic patients from normal subjects, the area under the curve was 0.77. However, relative miR-424 levels were not correlated with disease activity markers including disease duration, body surface area and Psoriasis Area and Severity Index. Hair root miR-424 was not useful for evaluating both diagnosis and severity of the disease. Our results indicated hair shaft miR-424 levels may be useful as a diagnostic marker of psoriasis.
    The Journal of Dermatology 03/2014; 41(5). DOI:10.1111/1346-8138.12460 · 2.35 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: microRNA (miRNA) is a family of non-coding RNAs, which consists of 19-25 nucleotides and regulates the expression of approximately 30% of human protein-coding mRNAs. miRNAs can bind to complementary sequences of the three prime untranslated regions of target mRNAs, leading to the modulation of gene expression. By altering target expression, miRNAs can affect various cellular activities including cell proliferation and cell development in vitro or carcinogenesis and immune response in vivo. A lot of researches have paid attention to the possibility that miRNAs play a role in the pathogenesis of various human disorders including skin diseases. For example, miR-29a down-regulation is thought to mediate the posttranscriptional up-regulation of collagens, which contributes to the tissue fibrosis in scleroderma. In addition, recent studies indicate that extracellular miRNA levels may be useful for the diagnosis and/or the estimation of disease activity of skin diseases. miR-150 levels were significantly decreased in sera of scleroderma patients, and were inversely correlated with the prevalence of pitting scars/ulcers and the incidence of anti-topoisomerase I antibody. Currently, the therapeutic value of miRNAs for the treatment of human diseases is under evaluation in animal models. let-7a can be overexpressed in the mouse skin by intermittent intraperitoneal miRNA injection, and skin fibrosis induced by bleomycin in mice can be improved by the supplementation of let-7a. This paper discusses the possible applications of miRNAs in the clarification of pathogenesis, diagnosis, evaluation of disease activity and treatment of skin diseases.
    Journal of dermatological science 01/2014; DOI:10.1016/j.jdermsci.2014.01.004 · 3.71 Impact Factor

Full-text (3 Sources)

Available from
Sep 8, 2014