Immune cells lacking Y chromosome show dysregulation of autosomal gene expression
| Autor: | Behrooz Torabi Moghadam, Noémi Nagy, Karolina Bukowska-Strakova, Ulf Gyllensten, Vilmantas Giedraitis, Erin Oerton, Edyta Rychlicka-Buniowska, Łukasz Bełch, Lars Forsberg, Hanna Davies, Jarosław Baran, Jessica Nordlund, Stefan Enroth, Åsa Johansson, Maciej Siedlar, Tomasz Grodzicki, Kazimierz Weglarczyk, Alicja Klich-Rączka, Lena Kilander, Jan P. Dumanski, Alicja Jozkowicz, Marcus Danielsson, John R. B. Perry, Janusz Ryś, Arkadiusz Piotrowski, Stefan Imreh, Janusz Jaszczyński, Jonas Mattisson, Martin Ingelsson, Adam Ameur, Paweł Olszewski, Piotr Chlosta, Jonatan Halvardson, Aleksandra Ambicka, Marcin Przewoźnik |
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| Přispěvatelé: | Dumanski, Jan P [0000-0002-1489-1452], Forsberg, Lars A [0000-0002-1701-755X], Apollo - University of Cambridge Repository, Dumanski, Jan P. [0000-0002-1489-1452], Forsberg, Lars A. [0000-0002-1701-755X] |
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
CD4-Positive T-Lymphocytes Male Cell type Biology medicine.disease_cause Y chromosome 03 medical and health sciences Cellular and Molecular Neuroscience 0302 clinical medicine Immune system Alzheimer Disease Gene expression medicine Leukocytes Humans LATE Molecular Biology Gene Differential gene expression Medicinsk genetik Pharmacology Genetics Mutation Chromosomes Human Y Mosaicism Mosaic loss of chromosome Y RNA Chromosome Prostatic Neoplasms LOY Cell Biology Killer Cells Natural 030104 developmental biology LOY-associated transcriptional effects Gene Expression Regulation Molecular Medicine Original Article Medical Genetics 030217 neurology & neurosurgery |
| Zdroj: | Cellular and Molecular Life Sciences |
| Popis: | Funder: Kjell och Märta Beijers Stiftelse (SE) Funder: Hjärnfonden; doi: http://dx.doi.org/10.13039/501100003792 Funder: Cancerfonden; doi: http://dx.doi.org/10.13039/501100002794 Funder: Vetenskapsrådet; doi: http://dx.doi.org/10.13039/501100004359 Funder: Alzheimerfonden; doi: http://dx.doi.org/10.13039/501100008599 Funder: Konung Gustaf V:s och Drottning Victorias Frimurarestiftelse (SE) Funder: Science for Life Laboratory (SE) Funder: Fundacja na rzecz Nauki Polskiej (PL) Funder: Uppsala University 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. |
| Databáze: | OpenAIRE |
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