Chromatin accessibility and cell cycle progression are controlled by the HDAC-associated Sin3B protein in murine hematopoietic stem cells
Abstract Background Blood homeostasis requires the daily production of millions of terminally differentiated effector cells that all originate from hematopoietic stem cells (HSCs). HSCs are rare and exhibit unique self-renewal and multipotent properties, which depend on their ability to maintain qui...
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| Language: | English |
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BMC
2024-01-01
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| Series: | Epigenetics & Chromatin |
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| Online Access: | https://doi.org/10.1186/s13072-024-00526-w |
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| author | Alexander Calderon Tamara Mestvirishvili Francesco Boccalatte Kelly V. Ruggles Gregory David |
| author_facet | Alexander Calderon Tamara Mestvirishvili Francesco Boccalatte Kelly V. Ruggles Gregory David |
| author_sort | Alexander Calderon |
| collection | DOAJ |
| description | Abstract Background Blood homeostasis requires the daily production of millions of terminally differentiated effector cells that all originate from hematopoietic stem cells (HSCs). HSCs are rare and exhibit unique self-renewal and multipotent properties, which depend on their ability to maintain quiescence through ill-defined processes. Defective control of cell cycle progression can eventually lead to bone marrow failure or malignancy. In particular, the molecular mechanisms tying cell cycle re-entry to cell fate commitment in HSCs remain elusive. Previous studies have identified chromatin coordination as a key regulator of differentiation in embryonic stem cells. Results Here, we utilized genetic inactivation of the chromatin-associated Sin3B protein to manipulate cell cycle control and found dysregulated chromatin accessibility and cell cycle progression in HSCs. Single cell transcriptional profiling of hematopoietic stem and progenitor cells (HSPCs) inactivated for Sin3B reveals aberrant progression through the G1 phase of the cell cycle, which correlates with the engagement of specific signaling pathways, including aberrant expression of cell adhesion molecules and the interferon signaling program in LT-HSCs. In addition, we uncover the Sin3B-dependent accessibility of genomic elements controlling HSC differentiation, which points to cell cycle progression possibly dictating the priming of HSCs for differentiation. Conclusions Our findings provide new insights into controlled cell cycle progression as a potential regulator of HSC lineage commitment through the modulation of chromatin features. |
| format | Article |
| id | doaj-art-8515337339434df2b9638b0d93aa5cfe |
| institution | DOAJ |
| issn | 1756-8935 |
| language | English |
| publishDate | 2024-01-01 |
| publisher | BMC |
| record_format | Article |
| series | Epigenetics & Chromatin |
| spelling | doaj-art-8515337339434df2b9638b0d93aa5cfe2025-08-20T03:06:05ZengBMCEpigenetics & Chromatin1756-89352024-01-0117111810.1186/s13072-024-00526-wChromatin accessibility and cell cycle progression are controlled by the HDAC-associated Sin3B protein in murine hematopoietic stem cellsAlexander Calderon0Tamara Mestvirishvili1Francesco Boccalatte2Kelly V. Ruggles3Gregory David4Department of Biochemistry and Molecular Pharmacology, New York University Grossman School of Medicine, NYU Langone HealthDepartment of Medicine, New York University Grossman School of Medicine, NYU Langone HealthDepartment of Pathology, New York University Grossman School of Medicine, NYU Langone HealthDepartment of Medicine, New York University Grossman School of Medicine, NYU Langone HealthDepartment of Biochemistry and Molecular Pharmacology, New York University Grossman School of Medicine, NYU Langone HealthAbstract Background Blood homeostasis requires the daily production of millions of terminally differentiated effector cells that all originate from hematopoietic stem cells (HSCs). HSCs are rare and exhibit unique self-renewal and multipotent properties, which depend on their ability to maintain quiescence through ill-defined processes. Defective control of cell cycle progression can eventually lead to bone marrow failure or malignancy. In particular, the molecular mechanisms tying cell cycle re-entry to cell fate commitment in HSCs remain elusive. Previous studies have identified chromatin coordination as a key regulator of differentiation in embryonic stem cells. Results Here, we utilized genetic inactivation of the chromatin-associated Sin3B protein to manipulate cell cycle control and found dysregulated chromatin accessibility and cell cycle progression in HSCs. Single cell transcriptional profiling of hematopoietic stem and progenitor cells (HSPCs) inactivated for Sin3B reveals aberrant progression through the G1 phase of the cell cycle, which correlates with the engagement of specific signaling pathways, including aberrant expression of cell adhesion molecules and the interferon signaling program in LT-HSCs. In addition, we uncover the Sin3B-dependent accessibility of genomic elements controlling HSC differentiation, which points to cell cycle progression possibly dictating the priming of HSCs for differentiation. Conclusions Our findings provide new insights into controlled cell cycle progression as a potential regulator of HSC lineage commitment through the modulation of chromatin features.https://doi.org/10.1186/s13072-024-00526-wHematopoiesisCell cycleDifferentiationStem cellsChromatin |
| spellingShingle | Alexander Calderon Tamara Mestvirishvili Francesco Boccalatte Kelly V. Ruggles Gregory David Chromatin accessibility and cell cycle progression are controlled by the HDAC-associated Sin3B protein in murine hematopoietic stem cells Epigenetics & Chromatin Hematopoiesis Cell cycle Differentiation Stem cells Chromatin |
| title | Chromatin accessibility and cell cycle progression are controlled by the HDAC-associated Sin3B protein in murine hematopoietic stem cells |
| title_full | Chromatin accessibility and cell cycle progression are controlled by the HDAC-associated Sin3B protein in murine hematopoietic stem cells |
| title_fullStr | Chromatin accessibility and cell cycle progression are controlled by the HDAC-associated Sin3B protein in murine hematopoietic stem cells |
| title_full_unstemmed | Chromatin accessibility and cell cycle progression are controlled by the HDAC-associated Sin3B protein in murine hematopoietic stem cells |
| title_short | Chromatin accessibility and cell cycle progression are controlled by the HDAC-associated Sin3B protein in murine hematopoietic stem cells |
| title_sort | chromatin accessibility and cell cycle progression are controlled by the hdac associated sin3b protein in murine hematopoietic stem cells |
| topic | Hematopoiesis Cell cycle Differentiation Stem cells Chromatin |
| url | https://doi.org/10.1186/s13072-024-00526-w |
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