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• Hasselbalch HC (2014) A role of NF-E2 in chronic inflammation and clonal evolution in essential thrombocythemia, polycythemia vera and myelofibrosis?

Schema {🗺️}

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         headline:DNA methylation patterns contribute to changes of cellular differentiation pathways in leukocytes with LOY from patients with Alzheimer´s disease
         description:Alzheimer’s disease (AD) is a common and increasing societal problem due to the extending human lifespan. In males, loss of chromosome Y (LOY) in leukocytes is strongly associated with AD. We studied here DNA methylation and RNA expression in sorted monocytes and granulocytes with and without LOY from male AD patients. Through multi-omic analysis, we identified new candidate genes along with those previously associated with AD. Global analyses of DNA methylation in samples with LOY vs. normal state showed that hypomethylation dominated both in granulocytes and monocytes. Our findings highlight LOY-related differences in DNA methylation that occur in gene regulatory regions. Specifically, we observed alterations in key genes involved in leukocyte differentiation: FLI1, involved in early hematopoiesis; RUNX1, essential for blood cell development; RARA, regulating gene expression in response to retinoic acid; CANX, crucial for protein folding; CEBPB, a transcription factor important for immune responses; and MYADM, implicated in cell adhesion and migration. Moreover, protein–protein interaction analysis in granulocytes identified that products of two of these genes, CANX and CEBPB, are key hub proteins. This research underscores the potential of multi-omic approach in pure hematopoietic cell populations to uncover the molecular underpinnings of AD. Finally, our results link previous analysis showing impact of LOY on leukocyte differentiation, LOY-associated transcriptional dysregulation and GWAS studies of LOY.
         datePublished:2025-02-25T00:00:00Z
         dateModified:2025-02-25T00:00:00Z
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            DNA methylation
            CpG dinucleotide methylation
            Loss of chromosome Y
            Alzheimer’s disease
            Gene expression regulation
            Cell Biology
            Biomedicine
            general
            Life Sciences
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      headline:DNA methylation patterns contribute to changes of cellular differentiation pathways in leukocytes with LOY from patients with Alzheimer´s disease
      description:Alzheimer’s disease (AD) is a common and increasing societal problem due to the extending human lifespan. In males, loss of chromosome Y (LOY) in leukocytes is strongly associated with AD. We studied here DNA methylation and RNA expression in sorted monocytes and granulocytes with and without LOY from male AD patients. Through multi-omic analysis, we identified new candidate genes along with those previously associated with AD. Global analyses of DNA methylation in samples with LOY vs. normal state showed that hypomethylation dominated both in granulocytes and monocytes. Our findings highlight LOY-related differences in DNA methylation that occur in gene regulatory regions. Specifically, we observed alterations in key genes involved in leukocyte differentiation: FLI1, involved in early hematopoiesis; RUNX1, essential for blood cell development; RARA, regulating gene expression in response to retinoic acid; CANX, crucial for protein folding; CEBPB, a transcription factor important for immune responses; and MYADM, implicated in cell adhesion and migration. Moreover, protein–protein interaction analysis in granulocytes identified that products of two of these genes, CANX and CEBPB, are key hub proteins. This research underscores the potential of multi-omic approach in pure hematopoietic cell populations to uncover the molecular underpinnings of AD. Finally, our results link previous analysis showing impact of LOY on leukocyte differentiation, LOY-associated transcriptional dysregulation and GWAS studies of LOY.
      datePublished:2025-02-25T00:00:00Z
      dateModified:2025-02-25T00:00:00Z
      pageStart:1
      pageEnd:18
      license:http://creativecommons.org/licenses/by/4.0/
      sameAs:https://doi.org/10.1007/s00018-025-05618-8
      keywords:
         DNA methylation
         CpG dinucleotide methylation
         Loss of chromosome Y
         Alzheimer’s disease
         Gene expression regulation
         Cell Biology
         Biomedicine
         general
         Life Sciences
         Biochemistry
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      author:
            name:Marcin Jąkalski
            url:http://orcid.org/0000-0002-5481-9148
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         name:Department of Immunology, Genetics and Pathology and Science for Life Laboratory, Uppsala University, Uppsala, Sweden
         type:PostalAddress
ImageObject:
      url:https://www.springernature.com/app-sn/public/images/logo-springernature.png
Person:
      name:Marcin Jąkalski
      url:http://orcid.org/0000-0002-5481-9148
      affiliation:
            name:Medical University of Gdańsk
            address:
               name:3P-Medicine Laboratory, Medical University of Gdańsk, Gdańsk, Poland
               type:PostalAddress
            type:Organization
      email:[email protected]
      name:Bożena Bruhn-Olszewska
      url:http://orcid.org/0000-0003-2141-0247
      affiliation:
            name:Uppsala University
            address:
               name:Department of Immunology, Genetics and Pathology and Science for Life Laboratory, Uppsala University, Uppsala, Sweden
               type:PostalAddress
            type:Organization
      email:[email protected]
      name:Edyta Rychlicka-Buniowska
      affiliation:
            name:Medical University of Gdańsk
            address:
               name:3P-Medicine Laboratory, Medical University of Gdańsk, Gdańsk, Poland
               type:PostalAddress
            type:Organization
      name:Hanna Davies
      affiliation:
            name:Uppsala University
            address:
               name:Department of Immunology, Genetics and Pathology and Science for Life Laboratory, Uppsala University, Uppsala, Sweden
               type:PostalAddress
            type:Organization
      name:Daniil Sarkisyan
      affiliation:
            name:Uppsala University
            address:
               name:Department of Immunology, Genetics and Pathology and Science for Life Laboratory, Uppsala University, Uppsala, Sweden
               type:PostalAddress
            type:Organization
      name:Maciej Siedlar
      affiliation:
            name:Jagiellonian University, Collegium Medicum
            address:
               name:Department of Clinical Immunology, Institute of Paediatrics, Jagiellonian University, Collegium Medicum, Kraków, Poland
               type:PostalAddress
            type:Organization
      name:Jarosław Baran
      affiliation:
            name:Jagiellonian University, Collegium Medicum
            address:
               name:Department of Clinical Immunology, Institute of Paediatrics, Jagiellonian University, Collegium Medicum, Kraków, Poland
               type:PostalAddress
            type:Organization
      name:Kazimierz Węglarczyk
      affiliation:
            name:Jagiellonian University, Collegium Medicum
            address:
               name:Department of Clinical Immunology, Institute of Paediatrics, Jagiellonian University, Collegium Medicum, Kraków, Poland
               type:PostalAddress
            type:Organization
      name:Janusz Jaszczynski
      affiliation:
            name:Maria Skłodowska-Curie National Research Institute of Oncology
            address:
               name:Department of Urology, Maria Skłodowska-Curie National Research Institute of Oncology, Kraków, Poland
               type:PostalAddress
            type:Organization
      name:Janusz Ryś
      affiliation:
            name:Maria Skłodowska-Curie National Research Institute of Oncology
            address:
               name:Department of Tumor Pathology, Maria Skłodowska-Curie National Research Institute of Oncology, Kraków, Poland
               type:PostalAddress
            type:Organization
      name:Vilmantas Gedraitis
      affiliation:
            name:Uppsala University
            address:
               name:Department of Public Health and Caring Sciences/Geriatrics, Uppsala University, Uppsala, Sweden
               type:PostalAddress
            type:Organization
      name:Natalia Filipowicz
      affiliation:
            name:Medical University of Gdańsk
            address:
               name:3P-Medicine Laboratory, Medical University of Gdańsk, Gdańsk, Poland
               type:PostalAddress
            type:Organization
      name:Alicja Klich-Rączka
      affiliation:
            name:Jagiellonian University, Collegium Medicum
            address:
               name:Department and Clinic of Internal Medicine and Gerontology, Jagiellonian University, Collegium Medicum, Kraków, Poland
               type:PostalAddress
            type:Organization
      name:Lena Kilander
      affiliation:
            name:Uppsala University
            address:
               name:Department of Public Health and Caring Sciences/Geriatrics, Uppsala University, Uppsala, Sweden
               type:PostalAddress
            type:Organization
      name:Martin Ingelsson
      affiliation:
            name:Uppsala University
            address:
               name:Department of Public Health and Caring Sciences/Geriatrics, Uppsala University, Uppsala, Sweden
               type:PostalAddress
            type:Organization
            name:University Health Network
            address:
               name:Krembil Brain Institute, University Health Network, Toronto, Canada
               type:PostalAddress
            type:Organization
            name:University of Toronto
            address:
               name:Tanz Centre for Research in Neurodegenerative Diseases, Departments of Medicine and Laboratory Medicine & Pathobiology, University of Toronto, Toronto, Canada
               type:PostalAddress
            type:Organization
      name:Jan P. Dumanski
      url:http://orcid.org/0000-0002-1489-1452
      affiliation:
            name:Medical University of Gdańsk
            address:
               name:3P-Medicine Laboratory, Medical University of Gdańsk, Gdańsk, Poland
               type:PostalAddress
            type:Organization
            name:Uppsala University
            address:
               name:Department of Immunology, Genetics and Pathology and Science for Life Laboratory, Uppsala University, Uppsala, Sweden
               type:PostalAddress
            type:Organization
      email:[email protected]
PostalAddress:
      name:3P-Medicine Laboratory, Medical University of Gdańsk, Gdańsk, Poland
      name:Department of Immunology, Genetics and Pathology and Science for Life Laboratory, Uppsala University, Uppsala, Sweden
      name:3P-Medicine Laboratory, Medical University of Gdańsk, Gdańsk, Poland
      name:Department of Immunology, Genetics and Pathology and Science for Life Laboratory, Uppsala University, Uppsala, Sweden
      name:Department of Immunology, Genetics and Pathology and Science for Life Laboratory, Uppsala University, Uppsala, Sweden
      name:Department of Clinical Immunology, Institute of Paediatrics, Jagiellonian University, Collegium Medicum, Kraków, Poland
      name:Department of Clinical Immunology, Institute of Paediatrics, Jagiellonian University, Collegium Medicum, Kraków, Poland
      name:Department of Clinical Immunology, Institute of Paediatrics, Jagiellonian University, Collegium Medicum, Kraków, Poland
      name:Department of Urology, Maria Skłodowska-Curie National Research Institute of Oncology, Kraków, Poland
      name:Department of Tumor Pathology, Maria Skłodowska-Curie National Research Institute of Oncology, Kraków, Poland
      name:Department of Public Health and Caring Sciences/Geriatrics, Uppsala University, Uppsala, Sweden
      name:3P-Medicine Laboratory, Medical University of Gdańsk, Gdańsk, Poland
      name:Department and Clinic of Internal Medicine and Gerontology, Jagiellonian University, Collegium Medicum, Kraków, Poland
      name:Department of Public Health and Caring Sciences/Geriatrics, Uppsala University, Uppsala, Sweden
      name:Department of Public Health and Caring Sciences/Geriatrics, Uppsala University, Uppsala, Sweden
      name:Krembil Brain Institute, University Health Network, Toronto, Canada
      name:Tanz Centre for Research in Neurodegenerative Diseases, Departments of Medicine and Laboratory Medicine & Pathobiology, University of Toronto, Toronto, Canada
      name:3P-Medicine Laboratory, Medical University of Gdańsk, Gdańsk, Poland
      name:Department of Immunology, Genetics and Pathology and Science for Life Laboratory, Uppsala University, Uppsala, Sweden

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