| 1. |
- Aevarsson, Arnthór, et al.
(author)
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Going to extremes - a metagenomic journey into the dark matter of life
- 2021
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In: FEMS Microbiology Letters. - : Oxford University Press (OUP). - 1574-6968. ; 368:12
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Research review (peer-reviewed)abstract
- The Virus-X-Viral Metagenomics for Innovation Value-project was a scientific expedition to explore and exploit uncharted territory of genetic diversity in extreme natural environments such as geothermal hot springs and deep-sea ocean ecosystems. Specifically, the project was set to analyse and exploit viral metagenomes with the ultimate goal of developing new gene products with high innovation value for applications in biotechnology, pharmaceutical, medical, and the life science sectors. Viral gene pool analysis is also essential to obtain fundamental insight into ecosystem dynamics and to investigate how viruses influence the evolution of microbes and multicellular organisms. The Virus-X Consortium, established in 2016, included experts from eight European countries. The unique approach based on high throughput bioinformatics technologies combined with structural and functional studies resulted in the development of a biodiscovery pipeline of significant capacity and scale. The activities within the Virus-X consortium cover the entire range from bioprospecting and methods development in bioinformatics to protein production and characterisation, with the final goal of translating our results into new products for the bioeconomy. The significant impact the consortium made in all of these areas was possible due to the successful cooperation between expert teams that worked together to solve a complex scientific problem using state-of-the-art technologies as well as developing novel tools to explore the virosphere, widely considered as the last great frontier of life.
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| 2. |
- Kurek, Magdalena
(author)
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Laminins in stemness and germ cell development in human
- 2019
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Doctoral thesis (other academic/artistic)abstract
- Stem cell niches regulate the fine balance between self-renewal and differentiation of various stem cells. Although crucial hallmarks of stem cell niches, such as the mechanical signalling, neural inputs communicating distant cues, the proximity to blood vessels and the structural support by the surrounding basement membrane (BM), have been evaluated in different niches, little much attention has been directed to the specific composition of the BM. As a crucial component of the BM, laminins have shown major importance for physiological development, with lack of laminin α (LAMA) 1 and 5 resulting in major developmental disruptions. Although, the importance of laminin 521 (LN521) in the embryonic inner cell mass (ICM) from which pluripotent stem cells (PSCs) are derived and in tissues such as the pancreas, nervous and muscular system and vasculature has been established, recent mass spectrometry studies of decellularized adult testicular tissue have suggested the presence of LN521 as well as LN121 in the testis. Hence, we aimed to investigate the role of LN521 in stemness behaviour of human embryonic stem cells (hESCs) and human induced pluripotent stem cells (hiPSCs) as well as the potential role of LN521 and 121 in the testicular stem cell niche. Utilizing five human foreskin fibroblast cultured hESC lines, pluripotency after short-term culture on LN521, LN121 and Matrigel was evaluated. We found that LN521, not only supports cell adhesion and stem cell maintenance but further homogenises the pluripotency expression pattern between the cell lines. Further, by applying LN521 as a culture substrate for derivation of Klinefelter syndrome (KS) hiPSCs, we demonstrated the beneficial effect of LN521 on fibroblast reprogramming efficiency. By utilizing LN521 as culture substrate of KS derived hiPSCs we additionally revealed a similar X chromosome inactivation (XCI) behaviour to female cultured PSCs, observed by either the maintenance of XCI with one inactive X chromosome or erosion of XCI. Finally, testicular laminin composition was evaluated during gonadal development and its importance for spermatogonial stem cell maintenance evaluated. We found LAMA 5 to be restricted to the vasculature while LAMA 1 was the sole α laminin chain of prenatal and preand peripubertal seminiferous cords and tubules. LAMA 1 was further restricted to the innermost basal lamina of the adult seminiferous tubules. Interestingly, LAMA 1 loss, as a result of inadequate culture conditions, correlated with a loss of germ cells. In conclusion we demonstrated the importance of LN521 in stem cell maintenance of hESCs and hiPSCs and revealed a correlation between germ cell maintenance and presence of LN121.
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| 3. |
- Kurek, Magdalena, et al.
(author)
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Spermatogonia Loss Correlates with LAMA 1 Expression in Human Prepubertal Testes Stored for Fertility Preservation
- 2021
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In: Cells. - : MDPI AG. - 2073-4409. ; 10:2
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Journal article (peer-reviewed)abstract
- Fertility preservation for male childhood cancer survivors not yet capable of producing mature spermatozoa, relies on experimental approaches such as testicular explant culture. Although the first steps in somatic maturation can be observed in human testicular explant cultures, germ cell depletion is a common obstacle. Hence, understanding the spermatogonial stem cell (SSC) niche environment and in particular, specific components such as the seminiferous basement membrane (BM) will allow progression of testicular explant cultures. Here, we revealed that the seminiferous BM is established from 6 weeks post conception with the expression of laminin alpha 1 (LAMA 1) and type IV collagen, which persist as key components throughout development. With prepubertal testicular explant culture we found that seminiferous LAMA 1 expression is disrupted and depleted with culture time correlating with germ cell loss. These findings highlight the importance of LAMA 1 for the human SSC niche and its sensitivity to culture conditions.
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