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Träfflista för sökning "WFRF:(Danielsson Martin 1982 ) ;pers:(Kilander Lena)"

Sökning: WFRF:(Danielsson Martin 1982 ) > Kilander Lena

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1.
  • Dumanski, Jan P., et al. (författare)
  • Immune cells lacking Y chromosome show dysregulation of autosomal gene expression
  • 2021
  • Ingår i: Cellular and Molecular Life Sciences (CMLS). - : Springer. - 1420-682X .- 1420-9071. ; 78:8, s. 4019-4033
  • Tidskriftsartikel (refereegranskat)abstract
    • Epidemiological investigations show that mosaic loss of chromosome Y (LOY) in leukocytes is associated with earlier mortality and morbidity from many diseases in men. LOY is the most common acquired mutation and is associated with aberrant clonal expansion of cells, yet it remains unclear whether this mosaicism exerts a direct physiological effect. We studied DNA and RNA from leukocytes in sorted- and single-cells in vivo and in vitro. DNA analyses of sorted cells showed that men diagnosed with Alzheimer’s disease was primarily affected with LOY in NK cells whereas prostate cancer patients more frequently displayed LOY in CD4 + T cells and granulocytes. Moreover, bulk and single-cell RNA sequencing in leukocytes allowed scoring of LOY from mRNA data and confirmed considerable variation in the rate of LOY across individuals and cell types. LOY-associated transcriptional effect (LATE) was observed in ~ 500 autosomal genes showing dysregulation in leukocytes with LOY. The fraction of LATE genes within specific cell types was substantially larger than the fraction of LATE genes shared between different subsets of leukocytes, suggesting that LOY might have pleiotropic effects. LATE genes are involved in immune functions but also encode proteins with roles in other diverse biological processes. Our findings highlight a surprisingly broad role for chromosome Y, challenging the view of it as a “genetic wasteland”, and support the hypothesis that altered immune function in leukocytes could be a mechanism linking LOY to increased risk for disease.
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2.
  • Forsberg, Lars A., 1974-, et al. (författare)
  • Mosaic loss of chromosome Y in leukocytes matters
  • 2019
  • Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 51:1, s. 4-7
  • Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
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3.
  • Mattisson, Jonas, et al. (författare)
  • Leukocytes with chromosome Y loss have reduced abundance of the cell surface immunoprotein CD99
  • 2021
  • Ingår i: Scientific Reports. - : Springer Nature. - 2045-2322. ; 11:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Mosaic loss of chromosome Y (LOY) in immune cells is a male-specific mutation associated with increased risk for morbidity and mortality. The CD99 gene, positioned in the pseudoautosomal regions of chromosomes X and Y, encodes a cell surface protein essential for several key properties of leukocytes and immune system functions. Here we used CITE-seq for simultaneous quantification of CD99 derived mRNA and cell surface CD99 protein abundance in relation to LOY in single cells. The abundance of CD99 molecules was lower on the surfaces of LOY cells compared with cells without this aneuploidy in all six types of leukocytes studied, while the abundance of CD proteins encoded by genes located on autosomal chromosomes were independent from LOY. These results connect LOY in single cells with immune related cellular properties at the protein level, providing mechanistic insight regarding disease vulnerability in men affected with mosaic chromosome Y loss in blood leukocytes.
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