Age-Associated Decrease of the Histone Methyltransferase SUV39H1 in HSC Perturbs Heterochromatin and B Lymphoid Differentiation
Summary: The capacity of hematopoietic stem cells (HSC) to generate B lymphocytes declines with age, contributing to impaired immune function in the elderly. Here we show that the histone methyltransferase SUV39H1 plays an important role in human B lymphoid differentiation and that expression of SUV...
| Main Authors: | , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2016-06-01
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| Series: | Stem Cell Reports |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2213671116300625 |
| _version_ | 1818256509246636032 |
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| author | Dounia Djeghloul Klaudia Kuranda Isabelle Kuzniak Daniela Barbieri Irina Naguibneva Caroline Choisy Jean-Christophe Bories Christine Dosquet Marika Pla Valérie Vanneaux Gérard Socié Françoise Porteu David Garrick Michele Goodhardt |
| author_facet | Dounia Djeghloul Klaudia Kuranda Isabelle Kuzniak Daniela Barbieri Irina Naguibneva Caroline Choisy Jean-Christophe Bories Christine Dosquet Marika Pla Valérie Vanneaux Gérard Socié Françoise Porteu David Garrick Michele Goodhardt |
| author_sort | Dounia Djeghloul |
| collection | DOAJ |
| description | Summary: The capacity of hematopoietic stem cells (HSC) to generate B lymphocytes declines with age, contributing to impaired immune function in the elderly. Here we show that the histone methyltransferase SUV39H1 plays an important role in human B lymphoid differentiation and that expression of SUV39H1 decreases with age in both human and mouse HSC, leading to a global reduction in H3K9 trimethylation and perturbed heterochromatin function. Further, we demonstrate that SUV39H1 is a target of microRNA miR-125b, a known regulator of HSC function, and that expression of miR-125b increases with age in human HSC. Overexpression of miR-125b and inhibition of SUV39H1 in young HSC induced loss of B cell potential. Conversely, both inhibition of miR-125 and enforced expression of SUV39H1 improved the capacity of HSC from elderly individuals to generate B cells. Our findings highlight the importance of heterochromatin regulation in HSC aging and B lymphopoiesis. : Aging is associated with a decline in the capacity of hematopoietic stem cells (HSC) to generate B lymphocytes. Goodhardt and colleaguesdemonstrate that an age-associated increase of the microRNA miR-125b in HSC targets the histone methyltransferase SUV39H1, leading to perturbed heterochromatin and a decline of B cell potential. This study suggests new targets to improve immune function in the elderly. |
| first_indexed | 2024-12-12T17:28:53Z |
| format | Article |
| id | doaj.art-2bfd3069f5604216847aab88774cdd80 |
| institution | Directory Open Access Journal |
| issn | 2213-6711 |
| language | English |
| last_indexed | 2024-12-12T17:28:53Z |
| publishDate | 2016-06-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Stem Cell Reports |
| spelling | doaj.art-2bfd3069f5604216847aab88774cdd802022-12-22T00:17:25ZengElsevierStem Cell Reports2213-67112016-06-0166970984Age-Associated Decrease of the Histone Methyltransferase SUV39H1 in HSC Perturbs Heterochromatin and B Lymphoid DifferentiationDounia Djeghloul0Klaudia Kuranda1Isabelle Kuzniak2Daniela Barbieri3Irina Naguibneva4Caroline Choisy5Jean-Christophe Bories6Christine Dosquet7Marika Pla8Valérie Vanneaux9Gérard Socié10Françoise Porteu11David Garrick12Michele Goodhardt13INSERM UMRS-1126, Institut Universitaire d’Hématologie, Université Paris Diderot, Paris, FranceINSERM UMRS-1126, Institut Universitaire d’Hématologie, Université Paris Diderot, Paris, FranceINSERM UMRS-1126, Institut Universitaire d’Hématologie, Université Paris Diderot, Paris, FranceINSERM UMRS-1170, Gustave Roussy Cancer Campus, Université Paris Sud - Université Paris-Saclay, Villejuif, FranceINSERM UMRS-967, Institut de Radiobiologie Cellulaire et Moléculaire, Commissariat à l'Energie Atomique, Fontenay-aux-Roses, FranceINSERM UMRS-1126, Institut Universitaire d’Hématologie, Université Paris Diderot, Paris, FranceINSERM UMRS-1126, Institut Universitaire d’Hématologie, Université Paris Diderot, Paris, FranceINSERM UMRS-1131, Institut Universitaire d’Hématologie, Université Paris Diderot, Paris, FranceINSERM UMRS-1131, Institut Universitaire d’Hématologie, Université Paris Diderot, Paris, FranceAP-HP Unité de Thérapie Cellulaire, Centre d’Investigation Clinique en Biothérapie Cellulaire and INSERM UMRS-1160, Université Paris Diderot, Paris, FranceAP-HP Hematology Transplantation and INSERM UMRS-1160, Université Paris Diderot, Paris, FranceINSERM UMRS-1170, Gustave Roussy Cancer Campus, Université Paris Sud - Université Paris-Saclay, Villejuif, FranceINSERM UMRS-1126, Institut Universitaire d’Hématologie, Université Paris Diderot, Paris, FranceINSERM UMRS-1126, Institut Universitaire d’Hématologie, Université Paris Diderot, Paris, France; Corresponding authorSummary: The capacity of hematopoietic stem cells (HSC) to generate B lymphocytes declines with age, contributing to impaired immune function in the elderly. Here we show that the histone methyltransferase SUV39H1 plays an important role in human B lymphoid differentiation and that expression of SUV39H1 decreases with age in both human and mouse HSC, leading to a global reduction in H3K9 trimethylation and perturbed heterochromatin function. Further, we demonstrate that SUV39H1 is a target of microRNA miR-125b, a known regulator of HSC function, and that expression of miR-125b increases with age in human HSC. Overexpression of miR-125b and inhibition of SUV39H1 in young HSC induced loss of B cell potential. Conversely, both inhibition of miR-125 and enforced expression of SUV39H1 improved the capacity of HSC from elderly individuals to generate B cells. Our findings highlight the importance of heterochromatin regulation in HSC aging and B lymphopoiesis. : Aging is associated with a decline in the capacity of hematopoietic stem cells (HSC) to generate B lymphocytes. Goodhardt and colleaguesdemonstrate that an age-associated increase of the microRNA miR-125b in HSC targets the histone methyltransferase SUV39H1, leading to perturbed heterochromatin and a decline of B cell potential. This study suggests new targets to improve immune function in the elderly.http://www.sciencedirect.com/science/article/pii/S2213671116300625 |
| spellingShingle | Dounia Djeghloul Klaudia Kuranda Isabelle Kuzniak Daniela Barbieri Irina Naguibneva Caroline Choisy Jean-Christophe Bories Christine Dosquet Marika Pla Valérie Vanneaux Gérard Socié Françoise Porteu David Garrick Michele Goodhardt Age-Associated Decrease of the Histone Methyltransferase SUV39H1 in HSC Perturbs Heterochromatin and B Lymphoid Differentiation Stem Cell Reports |
| title | Age-Associated Decrease of the Histone Methyltransferase SUV39H1 in HSC Perturbs Heterochromatin and B Lymphoid Differentiation |
| title_full | Age-Associated Decrease of the Histone Methyltransferase SUV39H1 in HSC Perturbs Heterochromatin and B Lymphoid Differentiation |
| title_fullStr | Age-Associated Decrease of the Histone Methyltransferase SUV39H1 in HSC Perturbs Heterochromatin and B Lymphoid Differentiation |
| title_full_unstemmed | Age-Associated Decrease of the Histone Methyltransferase SUV39H1 in HSC Perturbs Heterochromatin and B Lymphoid Differentiation |
| title_short | Age-Associated Decrease of the Histone Methyltransferase SUV39H1 in HSC Perturbs Heterochromatin and B Lymphoid Differentiation |
| title_sort | age associated decrease of the histone methyltransferase suv39h1 in hsc perturbs heterochromatin and b lymphoid differentiation |
| url | http://www.sciencedirect.com/science/article/pii/S2213671116300625 |
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