Disruption of erythroid nuclear opening and histone release in myelodysplastic syndromes
Abstract Mammalian terminal erythropoiesis involves several characteristic phenomena including chromatin condensation and enucleation. One of the newly identified features of terminal erythropoiesis in mouse is a dynamic nuclear opening and histone release process, which is required for chromatin co...
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| Format: | Article |
| Language: | English |
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Wiley
2019-03-01
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| Series: | Cancer Medicine |
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| Online Access: | https://doi.org/10.1002/cam4.1969 |
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| author | Baobing Zhao Hui Liu Yang Mei Yijie Liu Xu Han Jing Yang Amittha Wickrema Peng Ji |
| author_facet | Baobing Zhao Hui Liu Yang Mei Yijie Liu Xu Han Jing Yang Amittha Wickrema Peng Ji |
| author_sort | Baobing Zhao |
| collection | DOAJ |
| description | Abstract Mammalian terminal erythropoiesis involves several characteristic phenomena including chromatin condensation and enucleation. One of the newly identified features of terminal erythropoiesis in mouse is a dynamic nuclear opening and histone release process, which is required for chromatin condensation. However, it is unclear whether the same feature is present in human. Here, we use an in vitro human CD34‐positive hematopoietic stem and progenitor cell culture system and reveal that nuclear openings and histone release are also identified during human terminal erythropoiesis. In contrast to mouse in which each erythroblast contains a single opening, multiple nuclear openings are present in human erythroblast, particularly during the late‐stage differentiation. The nuclear opening and histone release process is mediated by caspase‐3. Inhibition of caspase‐3 blocks nuclear opening, histone release, chromatin condensation, and terminal differentiation. We confirm the finding of histone cytosolic release in paraffin‐embedded human bone marrow in vivo. Importantly, we find that patients with myelodysplastic syndrome (MDS) exhibit significant defects in histone release in the dysplastic erythroblasts. Our results reveal developmentally conserved nuclear envelop and histone dynamic changes in human terminal erythropoiesis and indicate that disruption of the histone release process plays a critical role in the pathogenesis of dyserythropoiesis in MDS. |
| format | Article |
| id | doaj-art-09ec23ad0c4941faa8cd2cc73078a213 |
| institution | Kabale University |
| issn | 2045-7634 |
| language | English |
| publishDate | 2019-03-01 |
| publisher | Wiley |
| record_format | Article |
| series | Cancer Medicine |
| spelling | doaj-art-09ec23ad0c4941faa8cd2cc73078a2132025-01-31T08:47:43ZengWileyCancer Medicine2045-76342019-03-01831169117410.1002/cam4.1969Disruption of erythroid nuclear opening and histone release in myelodysplastic syndromesBaobing Zhao0Hui Liu1Yang Mei2Yijie Liu3Xu Han4Jing Yang5Amittha Wickrema6Peng Ji7Department of Pathology, Feinberg School of Medicine Northwestern University Chicago IllinoisSection of Hematology/Oncology, Department of Medicine The University of Chicago Chicago IllinoisDepartment of Pathology, Feinberg School of Medicine Northwestern University Chicago IllinoisDepartment of Pathology, Feinberg School of Medicine Northwestern University Chicago IllinoisDepartment of Pathology, Feinberg School of Medicine Northwestern University Chicago IllinoisDepartment of Pathology, Feinberg School of Medicine Northwestern University Chicago IllinoisSection of Hematology/Oncology, Department of Medicine The University of Chicago Chicago IllinoisDepartment of Pathology, Feinberg School of Medicine Northwestern University Chicago IllinoisAbstract Mammalian terminal erythropoiesis involves several characteristic phenomena including chromatin condensation and enucleation. One of the newly identified features of terminal erythropoiesis in mouse is a dynamic nuclear opening and histone release process, which is required for chromatin condensation. However, it is unclear whether the same feature is present in human. Here, we use an in vitro human CD34‐positive hematopoietic stem and progenitor cell culture system and reveal that nuclear openings and histone release are also identified during human terminal erythropoiesis. In contrast to mouse in which each erythroblast contains a single opening, multiple nuclear openings are present in human erythroblast, particularly during the late‐stage differentiation. The nuclear opening and histone release process is mediated by caspase‐3. Inhibition of caspase‐3 blocks nuclear opening, histone release, chromatin condensation, and terminal differentiation. We confirm the finding of histone cytosolic release in paraffin‐embedded human bone marrow in vivo. Importantly, we find that patients with myelodysplastic syndrome (MDS) exhibit significant defects in histone release in the dysplastic erythroblasts. Our results reveal developmentally conserved nuclear envelop and histone dynamic changes in human terminal erythropoiesis and indicate that disruption of the histone release process plays a critical role in the pathogenesis of dyserythropoiesis in MDS.https://doi.org/10.1002/cam4.1969chromatin condensationenucleationerythropoiesismyelodysplastic syndromes |
| spellingShingle | Baobing Zhao Hui Liu Yang Mei Yijie Liu Xu Han Jing Yang Amittha Wickrema Peng Ji Disruption of erythroid nuclear opening and histone release in myelodysplastic syndromes Cancer Medicine chromatin condensation enucleation erythropoiesis myelodysplastic syndromes |
| title | Disruption of erythroid nuclear opening and histone release in myelodysplastic syndromes |
| title_full | Disruption of erythroid nuclear opening and histone release in myelodysplastic syndromes |
| title_fullStr | Disruption of erythroid nuclear opening and histone release in myelodysplastic syndromes |
| title_full_unstemmed | Disruption of erythroid nuclear opening and histone release in myelodysplastic syndromes |
| title_short | Disruption of erythroid nuclear opening and histone release in myelodysplastic syndromes |
| title_sort | disruption of erythroid nuclear opening and histone release in myelodysplastic syndromes |
| topic | chromatin condensation enucleation erythropoiesis myelodysplastic syndromes |
| url | https://doi.org/10.1002/cam4.1969 |
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