Hepatic Leukemia Factor Maintains Quiescence of Hematopoietic Stem Cells and Protects the Stem Cell Pool during Regeneration
Summary: The transcription factor hepatic leukemia factor (HLF) is strongly expressed in hematopoietic stem cells (HSCs) and is thought to influence both HSC self-renewal and leukemogenesis. However, the physiological role of HLF in hematopoiesis and HSC function is unclear. Here, we report that mic...
| Main Authors: | , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2017-12-01
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| Series: | Cell Reports |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124717317515 |
| _version_ | 1818218107923070976 |
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| author | Karolina Komorowska Alexander Doyle Martin Wahlestedt Agatheeswaran Subramaniam Shubhranshu Debnath Jun Chen Shamit Soneji Ben Van Handel Hanna K.A. Mikkola Kenichi Miharada David Bryder Jonas Larsson Mattias Magnusson |
| author_facet | Karolina Komorowska Alexander Doyle Martin Wahlestedt Agatheeswaran Subramaniam Shubhranshu Debnath Jun Chen Shamit Soneji Ben Van Handel Hanna K.A. Mikkola Kenichi Miharada David Bryder Jonas Larsson Mattias Magnusson |
| author_sort | Karolina Komorowska |
| collection | DOAJ |
| description | Summary: The transcription factor hepatic leukemia factor (HLF) is strongly expressed in hematopoietic stem cells (HSCs) and is thought to influence both HSC self-renewal and leukemogenesis. However, the physiological role of HLF in hematopoiesis and HSC function is unclear. Here, we report that mice lacking Hlf are viable with essentially normal hematopoietic parameters, including an intact HSC pool during steady-state hematopoiesis. In contrast, when challenged through transplantation, Hlf-deficient HSCs showed an impaired ability to reconstitute hematopoiesis and became gradually exhausted upon serial transplantation. Transcriptional profiling of Hlf-deficient HSCs revealed changes associated with enhanced cellular activation, and cell-cycle analysis demonstrated a significant reduction of quiescent HSCs. Accordingly, toxic insults targeting dividing cells completely eradicated the HSC pool in Hlf-deficient mice. In summary, our findings point to HLF as a critical regulator of HSC quiescence and as an essential factor for maintaining the HSC pool during regeneration. : Komorowska et al. report that the transcription factor HLF is required to maintain hematopoietic stem cell (HSC) function during regeneration. Moreover, Hlf-deficient HSCs are less quiescent. In accordance with this, toxic insults targeting dividing cells completely eradicate the HSC pool in Hlf-deficient mice. Keywords: HSC, transcription factor, HLF, quiescence, self-renewal, cell cycle, reconstitution, transplantation, 5FU, stress |
| first_indexed | 2024-12-12T07:18:31Z |
| format | Article |
| id | doaj.art-93653e5e1b494a609acf2a52b536dffe |
| institution | Directory Open Access Journal |
| issn | 2211-1247 |
| language | English |
| last_indexed | 2024-12-12T07:18:31Z |
| publishDate | 2017-12-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cell Reports |
| spelling | doaj.art-93653e5e1b494a609acf2a52b536dffe2022-12-22T00:33:26ZengElsevierCell Reports2211-12472017-12-01211235143523Hepatic Leukemia Factor Maintains Quiescence of Hematopoietic Stem Cells and Protects the Stem Cell Pool during RegenerationKarolina Komorowska0Alexander Doyle1Martin Wahlestedt2Agatheeswaran Subramaniam3Shubhranshu Debnath4Jun Chen5Shamit Soneji6Ben Van Handel7Hanna K.A. Mikkola8Kenichi Miharada9David Bryder10Jonas Larsson11Mattias Magnusson12Molecular Medicine and Gene Therapy, Lund Stem Cell Center, Lund University, BMC A12, 221 84, Lund, SwedenMolecular Medicine and Gene Therapy, Lund Stem Cell Center, Lund University, BMC A12, 221 84, Lund, SwedenMolecular Hematology, Lund Stem Cell Center, Lund University, BMC A12, 221 84, Lund, SwedenMolecular Medicine and Gene Therapy, Lund Stem Cell Center, Lund University, BMC A12, 221 84, Lund, SwedenMolecular Medicine and Gene Therapy, Lund Stem Cell Center, Lund University, BMC A12, 221 84, Lund, SwedenMolecular Medicine and Gene Therapy, Lund Stem Cell Center, Lund University, BMC A12, 221 84, Lund, SwedenMolecular Hematology, Lund Stem Cell Center, Lund University, BMC A12, 221 84, Lund, SwedenDepartment of Stem Cell Biology and Regenerative Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, USA; CarthroniX, Inc., Tarzana, CA 91356, USADepartment of Molecular, Cell and Developmental Biology, University of California, Los Angeles, Los Angeles, CA 90095, USAMolecular Medicine and Gene Therapy, Lund Stem Cell Center, Lund University, BMC A12, 221 84, Lund, SwedenMolecular Hematology, Lund Stem Cell Center, Lund University, BMC A12, 221 84, Lund, SwedenMolecular Medicine and Gene Therapy, Lund Stem Cell Center, Lund University, BMC A12, 221 84, Lund, SwedenMolecular Medicine and Gene Therapy, Lund Stem Cell Center, Lund University, BMC A12, 221 84, Lund, Sweden; Corresponding authorSummary: The transcription factor hepatic leukemia factor (HLF) is strongly expressed in hematopoietic stem cells (HSCs) and is thought to influence both HSC self-renewal and leukemogenesis. However, the physiological role of HLF in hematopoiesis and HSC function is unclear. Here, we report that mice lacking Hlf are viable with essentially normal hematopoietic parameters, including an intact HSC pool during steady-state hematopoiesis. In contrast, when challenged through transplantation, Hlf-deficient HSCs showed an impaired ability to reconstitute hematopoiesis and became gradually exhausted upon serial transplantation. Transcriptional profiling of Hlf-deficient HSCs revealed changes associated with enhanced cellular activation, and cell-cycle analysis demonstrated a significant reduction of quiescent HSCs. Accordingly, toxic insults targeting dividing cells completely eradicated the HSC pool in Hlf-deficient mice. In summary, our findings point to HLF as a critical regulator of HSC quiescence and as an essential factor for maintaining the HSC pool during regeneration. : Komorowska et al. report that the transcription factor HLF is required to maintain hematopoietic stem cell (HSC) function during regeneration. Moreover, Hlf-deficient HSCs are less quiescent. In accordance with this, toxic insults targeting dividing cells completely eradicate the HSC pool in Hlf-deficient mice. Keywords: HSC, transcription factor, HLF, quiescence, self-renewal, cell cycle, reconstitution, transplantation, 5FU, stresshttp://www.sciencedirect.com/science/article/pii/S2211124717317515 |
| spellingShingle | Karolina Komorowska Alexander Doyle Martin Wahlestedt Agatheeswaran Subramaniam Shubhranshu Debnath Jun Chen Shamit Soneji Ben Van Handel Hanna K.A. Mikkola Kenichi Miharada David Bryder Jonas Larsson Mattias Magnusson Hepatic Leukemia Factor Maintains Quiescence of Hematopoietic Stem Cells and Protects the Stem Cell Pool during Regeneration Cell Reports |
| title | Hepatic Leukemia Factor Maintains Quiescence of Hematopoietic Stem Cells and Protects the Stem Cell Pool during Regeneration |
| title_full | Hepatic Leukemia Factor Maintains Quiescence of Hematopoietic Stem Cells and Protects the Stem Cell Pool during Regeneration |
| title_fullStr | Hepatic Leukemia Factor Maintains Quiescence of Hematopoietic Stem Cells and Protects the Stem Cell Pool during Regeneration |
| title_full_unstemmed | Hepatic Leukemia Factor Maintains Quiescence of Hematopoietic Stem Cells and Protects the Stem Cell Pool during Regeneration |
| title_short | Hepatic Leukemia Factor Maintains Quiescence of Hematopoietic Stem Cells and Protects the Stem Cell Pool during Regeneration |
| title_sort | hepatic leukemia factor maintains quiescence of hematopoietic stem cells and protects the stem cell pool during regeneration |
| url | http://www.sciencedirect.com/science/article/pii/S2211124717317515 |
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