Zfp521 is essential for the quiescence and maintenance of adult hematopoietic stem cells under stress
Summary: Zinc finger protein 521 (Zfp521), a quiescent hematopoietic stem cell (HSC)-enriched transcription factor, is involved in the self-renewal and differentiation of fetal liver HSC. However, its role in adult hematopoiesis remains elusive. Here, we found that Zfp521 deletion did not inhibit ad...
| Main Authors: | , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2021-02-01
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| Series: | iScience |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2589004221000079 |
| _version_ | 1818329387069603840 |
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| author | Zhigang Li Xuemei Fu Weiru Wu Zhilong Liu Zhe Chen Chengfang Zhou Yuanyuan Liu Mei Kuang Fangfang Sun Feifei Xiao Yongxiu Huang Xiaojun Zhang Shijun Fan Xingqin Huang Guangling Zheng Jieping Chen Yu Hou |
| author_facet | Zhigang Li Xuemei Fu Weiru Wu Zhilong Liu Zhe Chen Chengfang Zhou Yuanyuan Liu Mei Kuang Fangfang Sun Feifei Xiao Yongxiu Huang Xiaojun Zhang Shijun Fan Xingqin Huang Guangling Zheng Jieping Chen Yu Hou |
| author_sort | Zhigang Li |
| collection | DOAJ |
| description | Summary: Zinc finger protein 521 (Zfp521), a quiescent hematopoietic stem cell (HSC)-enriched transcription factor, is involved in the self-renewal and differentiation of fetal liver HSC. However, its role in adult hematopoiesis remains elusive. Here, we found that Zfp521 deletion did not inhibit adult hematopoiesis under homeostatic conditions. In contrast, Zfp521-null chimeric mice showed significantly reduced pool size of HSC and hematopoietic progenitor cells associated with increased apoptosis and loss of quiescence. Competitive serial transplantation assays revealed that Zfp521 regulates HSC self-renewal and differentiation under regenerative stress. Mechanistically, Zfp521 transcriptionally repressed Rela expression by increasing H3K9ac and decreasing H3K9me3 levels in its promoter. Knockdown of Rela inhibited the hyper-activated NF-κB pathway and reversed the loss of quiescence in Zfp521-null HSC under stress. Thus, our results reveal a previously unrecognized role for Zfp521 as critical regulator of quiescence and self-renewal of HSC in adult hematopoiesis mediated at least partly by controlling Rela expression. |
| first_indexed | 2024-12-13T12:47:15Z |
| format | Article |
| id | doaj.art-8449ac46897549d2aa74847336daf02e |
| institution | Directory Open Access Journal |
| issn | 2589-0042 |
| language | English |
| last_indexed | 2024-12-13T12:47:15Z |
| publishDate | 2021-02-01 |
| publisher | Elsevier |
| record_format | Article |
| series | iScience |
| spelling | doaj.art-8449ac46897549d2aa74847336daf02e2022-12-21T23:45:27ZengElsevieriScience2589-00422021-02-01242102039Zfp521 is essential for the quiescence and maintenance of adult hematopoietic stem cells under stressZhigang Li0Xuemei Fu1Weiru Wu2Zhilong Liu3Zhe Chen4Chengfang Zhou5Yuanyuan Liu6Mei Kuang7Fangfang Sun8Feifei Xiao9Yongxiu Huang10Xiaojun Zhang11Shijun Fan12Xingqin Huang13Guangling Zheng14Jieping Chen15Yu Hou16Department of Hematology, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing 400038, ChinaDepartment of Hematology, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing 400038, ChinaDepartment of Hematology, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing 400038, ChinaDepartment of Hematology, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing 400038, ChinaDepartment of Hematology, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing 400038, ChinaDepartment of Hematology, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing 400038, ChinaDepartment of Hematology, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing 400038, ChinaDepartment of Hematology, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing 400038, ChinaDepartment of Hematology, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing 400038, ChinaDepartment of Hematology, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing 400038, ChinaDepartment of Hematology, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing 400038, ChinaDepartment of Hematology, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing 400038, ChinaMedical Research Center, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing 400038, ChinaDepartment of Hematology, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing 400038, ChinaDepartment of Radiology, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing 400038, ChinaDepartment of Hematology, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing 400038, China; Corresponding authorDepartment of Hematology, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing 400038, China; Corresponding authorSummary: Zinc finger protein 521 (Zfp521), a quiescent hematopoietic stem cell (HSC)-enriched transcription factor, is involved in the self-renewal and differentiation of fetal liver HSC. However, its role in adult hematopoiesis remains elusive. Here, we found that Zfp521 deletion did not inhibit adult hematopoiesis under homeostatic conditions. In contrast, Zfp521-null chimeric mice showed significantly reduced pool size of HSC and hematopoietic progenitor cells associated with increased apoptosis and loss of quiescence. Competitive serial transplantation assays revealed that Zfp521 regulates HSC self-renewal and differentiation under regenerative stress. Mechanistically, Zfp521 transcriptionally repressed Rela expression by increasing H3K9ac and decreasing H3K9me3 levels in its promoter. Knockdown of Rela inhibited the hyper-activated NF-κB pathway and reversed the loss of quiescence in Zfp521-null HSC under stress. Thus, our results reveal a previously unrecognized role for Zfp521 as critical regulator of quiescence and self-renewal of HSC in adult hematopoiesis mediated at least partly by controlling Rela expression.http://www.sciencedirect.com/science/article/pii/S2589004221000079Molecular BiologyCell BiologyStem Cell ResearchTranscriptomics |
| spellingShingle | Zhigang Li Xuemei Fu Weiru Wu Zhilong Liu Zhe Chen Chengfang Zhou Yuanyuan Liu Mei Kuang Fangfang Sun Feifei Xiao Yongxiu Huang Xiaojun Zhang Shijun Fan Xingqin Huang Guangling Zheng Jieping Chen Yu Hou Zfp521 is essential for the quiescence and maintenance of adult hematopoietic stem cells under stress iScience Molecular Biology Cell Biology Stem Cell Research Transcriptomics |
| title | Zfp521 is essential for the quiescence and maintenance of adult hematopoietic stem cells under stress |
| title_full | Zfp521 is essential for the quiescence and maintenance of adult hematopoietic stem cells under stress |
| title_fullStr | Zfp521 is essential for the quiescence and maintenance of adult hematopoietic stem cells under stress |
| title_full_unstemmed | Zfp521 is essential for the quiescence and maintenance of adult hematopoietic stem cells under stress |
| title_short | Zfp521 is essential for the quiescence and maintenance of adult hematopoietic stem cells under stress |
| title_sort | zfp521 is essential for the quiescence and maintenance of adult hematopoietic stem cells under stress |
| topic | Molecular Biology Cell Biology Stem Cell Research Transcriptomics |
| url | http://www.sciencedirect.com/science/article/pii/S2589004221000079 |
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