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Title:
Immune cells lacking Y chromosome show dysregulation of autosomal gene expression | Cellular and Molecular Life Sciences
Description:
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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Keywords {🔍}
loy, genes, cells, cell, pubmed, chromosome, article, expression, google, scholar, late, disease, cas, gene, blood, cancer, autosomal, immune, data, alzheimers, supplementary, loss, leukocytes, samples, patients, central, men, fig, analysis, types, identified, uppsala, rna, single, sorted, mosaic, university, msy, expressed, type, rnaseq, studied, dna, study, monocytes, performed, research, prostate, risk, kraków,
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cd45 + cd3 − cd4 − cd16 + cd56 + diapedesis-mediating receptor central article download pdf cd16 + /cd56 + nk cells compared age-related macular degeneration high-dimensional single-cell mapping common post-zygotic mutation confounding age-dependent process ficoll-paque gradient separation gamma-irradiated human fibroblasts gov/grc/human/data promote chromosome mis-segregation age-related cellular senescence perturbed cell-cycle processes turbo dna-free™ kit cd45 + cd3 + cd8 − cd4 + cd45 + cd3 + cd4 − cd8 + kidney cancer gm-ap protein–protein association networks variance-stabilizing transformation applied automated cell-type assignment single-cell rna sequencing life technology platform genome-wide experimental datasets chromosomes showing reduced y-loss-related pathogenesis privacy choices/manage cookies cd19 + b-lymphocytes missing snp&seq platform single-cell transcriptome analysis cd8 + t-cytotoxic lymphocytes tomasz grodzicki cray innovation ab snp-array probes located cd45 + cd3 − cd19 + edyta rychlicka-buniowska entrez gene ids viral life cycle thompson dj cdkn1c—genetically increased expression swedish research council full access hematopoietic stem cells article dumanski international lung cancer ugc technology platforms national genomics infrastructure caring sciences/geriatrics obtain permission directly immune cell activity
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headline:Immune cells lacking Y chromosome show dysregulation of autosomal gene expression
description: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.
datePublished:2021-04-10T00:00:00Z
dateModified:2021-04-10T00:00:00Z
pageStart:4019
pageEnd:4033
license:http://creativecommons.org/licenses/by/4.0/
sameAs:https://doi.org/10.1007/s00018-021-03822-w
keywords:
LOY
Mosaic loss of chromosome Y
Differential gene expression
LATE
LOY-associated transcriptional effects
Cell Biology
Biomedicine
general
Life Sciences
Biochemistry
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headline:Immune cells lacking Y chromosome show dysregulation of autosomal gene expression
description: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.
datePublished:2021-04-10T00:00:00Z
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pageStart:4019
pageEnd:4033
license:http://creativecommons.org/licenses/by/4.0/
sameAs:https://doi.org/10.1007/s00018-021-03822-w
keywords:
LOY
Mosaic loss of chromosome Y
Differential gene expression
LATE
LOY-associated transcriptional effects
Cell Biology
Biomedicine
general
Life Sciences
Biochemistry
image:
https://media.springernature.com/lw1200/springer-static/image/art%3A10.1007%2Fs00018-021-03822-w/MediaObjects/18_2021_3822_Fig1_HTML.png
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