Mus musculus
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA149219 | ENA |
REPOSITORIES: ENA
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Project description:PURPOSE: To provide a detailed gene expression profile of the normal postnatal mouse cornea. METHODS: Serial analysis of gene expression (SAGE) was performed on postnatal day (PN)9 and adult mouse (6 week) total corneas. The expression of selected genes was analyzed by in situ hybridization. RESULTS: A total of 64,272 PN9 and 62,206 adult tags were sequenced. Mouse corneal transcriptomes are composed of at least 19,544 and 18,509 unique mRNAs, respectively. One third of the unique tags were expressed at both stages, whereas a third was identified exclusively in PN9 or adult corneas. Three hundred thirty-four PN9 and 339 adult tags were enriched more than fivefold over other published nonocular libraries. Abundant transcripts were associated with metabolic functions, redox activities, and barrier integrity. Three members of the Ly-6/uPAR family whose functions are unknown in the cornea constitute more than 1% of the total mRNA. Aquaporin 5, epithelial membrane protein and glutathione-S-transferase (GST) omega-1, and GST alpha-4 mRNAs were preferentially expressed in distinct corneal epithelial layers, providing new markers for stratification. More than 200 tags were differentially expressed, of which 25 mediate transcription. CONCLUSIONS: In addition to providing a detailed profile of expressed genes in the PN9 and mature mouse cornea, the present SAGE data demonstrate dynamic changes in gene expression after eye opening and provide new probes for exploring corneal epithelial cell stratification, development, and function and for exploring the intricate relationship between programmed and environmentally induced gene expression in the cornea. Keywords: other
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Project description:Long non-coding RNAs (lncRNAs) are emerging as key molecules in regulating many biological processes and have been implicated in development and disease pathogenesis. Biomarkers of cancer and normal tissue response to treatment are of great interest in precision medicine and for public health and medical management of disasters such as assessing radiation injury following accidental or intentional exposure. Circulating and functional RNAs, including microRNAs (miRNAs) and lncRNAs, in whole blood and other body fluids represent potential valuable candidates as biomarkers. Early prediction of possible acute, intermediate, and delayed effects of radiation exposure will enable timely therapeutic interventions. To address whether lncRNAs could serve as biomarkers for radiation bio-dosimetry, we performed whole genome transcriptome analysis in a mouse model after whole body irradiation. Differential lncRNA expression patterns were evaluated at 16-, 24-, and 48-hour time points post irradiation in total RNA isolated from whole blood of mice exposed to 1, 2, 4, 8, and 12 Gy of gamma-rays. Sham irradiated animals served as controls. Significant alterations in the expression patterns of lncRNAs were observed after different radiation doses at the various timepoints. We identified several lncRNAs known for DNA damage response as well as immune response as radiation induced biomarkers. Long non-coding RNA targets of tumor protein 53 (P53), Trp53cor1, Dino, Pvt1 and Tug1 and an upstream regulator of p53, Meg3 were altered in response to radiation. Gm14005 (Morrbid) and Tmevpg1 were regulated by radiation across all time points and doses. These two lncRNAs have important potential as blood based radiation biomarkers; Gm14005 (Morrbid) has recently been shown to play a key role in inflammatory response while Tmevpg1 has been implicated in the regulation of interferon-gamma. Precise molecular biomarkers will not only enable the development and effective use of medical countermeasures but also may be used to detect and circumvent or mitigate normal tissue injury in cancer radiotherapy treatments.
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