Immune cells lacking Y chromosome have widespread dysregulation of autosomal genes
Immune cells lacking Y chromosome have widespread dysregulation of autosomal genes
Abstract Mosaic loss of chromosome Y (LOY) in leukocytes has been associated with many diseases, yet it remains unclear whether this form of clonal mosaicism exerts a direct physiological effect. Here we perform single-cell and bulk RNA sequencing in leukocytes, observing considerable variation in the rate of LOY across individuals, cell types and disease state. Cells with LOY demonstrated a profound degree of transcriptional dysregulation impacting ～500 autosomal genes. These genes are preferentially 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”. Furthermore, they support the hypothesis that altered immune function in leukocytes is a mechanism directly linking LOY to disease.
Gyllensten Ulf、Dumanski Jan P.、Davies Hanna、Rychlicka-Buniowska Edyta、Nagy Noemi、Danielsson Marcus、Oerton Erin、Przewo?nik Marcin、Be?ch ?ukasz、Kilander Lena、Ameur Adam、Siedlar Maciej、Enroth Stefan、Baran Jaros?aw、Ingelsson Martin、Ry? Janusz、Klich-R?czka Alicja、Grodzicki Tomasz、Nordlund Jessica、J¨?zkowicz Alicja、Jaszczy¨?ski Janusz、Piotrowski Arkadiusz、W?glarczyk Kazimierz、Perry John R. B.、Bukowska-Strakova Karolina、Olszewski Pawe?、Halvardson Jonatan、Forsberg Lars A.、Mattisson Jonas、Giedraitis Vilmantas、Imreh Stefan、Ambicka Aleksandra、Moghadam Behrooz Torabi、Ch?osta Piotr L.、Johansson ?sa
Dept. of Immunology, Genetics and Pathology and Science for Life Laboratory, Uppsala UniversityDept. of Immunology, Genetics and Pathology and Science for Life Laboratory, Uppsala University||Faculty of Pharmacy and 3P Medicine Laboratory, International Research Agendas Programme, Medical University of Gda¨?skDept. of Immunology, Genetics and Pathology and Science for Life Laboratory, Uppsala UniversityInternational Research Agendas Programme, 3P Medicine Laboratory, Medical University of Gda¨?skDept. of Cell and Molecular Biology, Karolinska InstitutetDept. of Immunology, Genetics and Pathology and Science for Life Laboratory, Uppsala UniversityMRC Epidemiology Unit, School of Clinical Medicine, University of CambridgeDept. of Tumour Pathology, Maria Sk?odowska-Curie Memorial Cancer Centre and Institute of Oncology, Krak¨?w BranchDept. and Clinic of Urology, Jagiellonian University, Collegium MedicumDept. of Public Health and Caring Sciences/ Geriatrics, Uppsala UniversityDept. of Immunology, Genetics and Pathology and Science for Life Laboratory, Uppsala UniversityDept. of Clinical Immunology, Institute of Paediatrics, Jagiellonian University, Collegium MedicumDept. of Immunology, Genetics and Pathology and Science for Life Laboratory, Uppsala UniversityDept. of Clinical Immunology, Institute of Paediatrics, Jagiellonian University, Collegium MedicumDept. of Public Health and Caring Sciences/ Geriatrics, Uppsala UniversityDept. of Tumour Pathology, Maria Sk?odowska-Curie Memorial Cancer Centre and Institute of Oncology, Krak¨?w BranchDept. and Clinic of Internal Medicine and Gerontology, Jagiellonian University, Collegium MedicumDept. and Clinic of Internal Medicine and Gerontology, Jagiellonian University, Collegium MedicumDept. of Medical Sciences, Uppsala UniversityDept. of Medical Biotechnology, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian UniversityDept. of Urology, Maria Sk?odowska-Curie Memorial Cancer Centre and Institute of Oncology, Krak¨?w BranchFaculty of Pharmacy and 3P Medicine Laboratory, International Research Agendas Programme, Medical University of Gda¨?skDept. of Clinical Immunology, Institute of Paediatrics, Jagiellonian University, Collegium MedicumMRC Epidemiology Unit, School of Clinical Medicine, University of CambridgeDept. of Clinical Immunology, Institute of Paediatrics, Jagiellonian University, Collegium MedicumInternational Research Agendas Programme, 3P Medicine Laboratory, Medical University of Gda¨?skDept. of Immunology, Genetics and Pathology and Science for Life Laboratory, Uppsala UniversityDept. of Immunology, Genetics and Pathology and Science for Life Laboratory, Uppsala University||The Beijer Laboratory, Uppsala UniversityDept. of Immunology, Genetics and Pathology and Science for Life Laboratory, Uppsala UniversityDept. of Public Health and Caring Sciences/ Geriatrics, Uppsala UniversityDept. Oncology-Pathology, Karolinska InstitutetDept. of Tumour Pathology, Maria Sk?odowska-Curie Memorial Cancer Centre and Institute of Oncology, Krak¨?w BranchDept. of Immunology, Genetics and Pathology and Science for Life Laboratory, Uppsala UniversityDept. and Clinic of Urology, Jagiellonian University, Collegium MedicumDept. of Immunology, Genetics and Pathology and Science for Life Laboratory, Uppsala University
基础医学遗传学细胞生物学
Gyllensten Ulf,Dumanski Jan P.,Davies Hanna,Rychlicka-Buniowska Edyta,Nagy Noemi,Danielsson Marcus,Oerton Erin,Przewo?nik Marcin,Be?ch ?ukasz,Kilander Lena,Ameur Adam,Siedlar Maciej,Enroth Stefan,Baran Jaros?aw,Ingelsson Martin,Ry? Janusz,Klich-R?czka Alicja,Grodzicki Tomasz,Nordlund Jessica,J¨?zkowicz Alicja,Jaszczy¨?ski Janusz,Piotrowski Arkadiusz,W?glarczyk Kazimierz,Perry John R. B.,Bukowska-Strakova Karolina,Olszewski Pawe?,Halvardson Jonatan,Forsberg Lars A.,Mattisson Jonas,Giedraitis Vilmantas,Imreh Stefan,Ambicka Aleksandra,Moghadam Behrooz Torabi,Ch?osta Piotr L.,Johansson ?sa.Immune cells lacking Y chromosome have widespread dysregulation of autosomal genes[EB/OL].(2025-03-28)[2025-05-01].https://www.biorxiv.org/content/10.1101/673459.点此复制
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