Comparison of endogenous retroviral RNA profiles from blood cells and plasma, between nonagenarians and young controls
Autio, Arttu (2018)
2018
Master's Degree Programme in Bioinformatics
Lääketieteen ja biotieteiden tiedekunta - Faculty of Medicine and Life Sciences
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Hyväksymispäivämäärä
2018-12-18
Julkaisun pysyvä osoite on
https://urn.fi/URN:NBN:fi:uta-201812313053
https://urn.fi/URN:NBN:fi:uta-201812313053
Tiivistelmä
Background: An estimated 8% of the human genome consists of integrated virus genomes that have been left over from past retroviral infections. These human endogenous retroviruses (HERV) have been ravaged by mutational decay, often over millions of years, and most have been rendered inactive. However, some still contain open reading frames and may even code for functional protein products. Upregulation of these retroelements has been observed in certain disease states and in aging mice.
Materials and Methods: PBMC and plasma samples were previously obtained from nonagenarians (n=7, age 90) and young controls (n=7, age 26-32, median age 28). RNA-sequencing of the samples was performed and the expression of endogenous human genes and HERV proviruses of the families HERV-K (HML-2) and HERV-W was quantified. This thesis work focused on the characterization and comparison of proviral expression values between the biological sources and across age groups.
Results: Proviral expression differed greatly between PBMCs and plasma. Age-associated significant differential expression of three HERV-K (HML-2) and one HERV-W provirus was found in PBMCs. Furthermore, hierarchical clustering of samples indicated aging-associated differences in proviral expression patterns. No age-associated differences in proviral expression could be found in plasma samples.
Conclusion: There are age-associated differences in the expression of HERV-K (HML-2) and HERV-W in PBMCs. Between sample differences in proviral expressions in plasma were too great to determine differences between age groups. The differing proviral expression between PBMC and plasma supports the hypothesis of enriched proviral cargo of extracellular vesicles (EV). It was not possible to determine with confidence the origin of the EVs in the plasma samples. Investigation of proviral expression using the same approach with larger datasets of RNA-sequencing data, potentially from external databases, could offer further insights.
Materials and Methods: PBMC and plasma samples were previously obtained from nonagenarians (n=7, age 90) and young controls (n=7, age 26-32, median age 28). RNA-sequencing of the samples was performed and the expression of endogenous human genes and HERV proviruses of the families HERV-K (HML-2) and HERV-W was quantified. This thesis work focused on the characterization and comparison of proviral expression values between the biological sources and across age groups.
Results: Proviral expression differed greatly between PBMCs and plasma. Age-associated significant differential expression of three HERV-K (HML-2) and one HERV-W provirus was found in PBMCs. Furthermore, hierarchical clustering of samples indicated aging-associated differences in proviral expression patterns. No age-associated differences in proviral expression could be found in plasma samples.
Conclusion: There are age-associated differences in the expression of HERV-K (HML-2) and HERV-W in PBMCs. Between sample differences in proviral expressions in plasma were too great to determine differences between age groups. The differing proviral expression between PBMC and plasma supports the hypothesis of enriched proviral cargo of extracellular vesicles (EV). It was not possible to determine with confidence the origin of the EVs in the plasma samples. Investigation of proviral expression using the same approach with larger datasets of RNA-sequencing data, potentially from external databases, could offer further insights.