Alkbh5 plays indispensable roles in maintaining self-renewal of hematopoietic stem cells
Alkbh5 is one of the primary demethylases responsible for reversing N6-methyladenosine (m6A) modifications on mRNAs, and it plays a crucial role in many physiological and pathological processes. Previous studies have shown that Alkbh5 is required for maintaining the function of leukemia stem cells b...
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Format: | Article |
Language: | English |
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De Gruyter
2023-08-01
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Series: | Open Medicine |
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Online Access: | https://doi.org/10.1515/med-2023-0766 |
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author | Yang Bijie Liu Yuanyuan Xiao Feifei Liu Zhilong Chen Zhe Li Zhigang Zhou Chengfang Kuang Mei Shu Yi Liu Shan Zou Lin |
author_facet | Yang Bijie Liu Yuanyuan Xiao Feifei Liu Zhilong Chen Zhe Li Zhigang Zhou Chengfang Kuang Mei Shu Yi Liu Shan Zou Lin |
author_sort | Yang Bijie |
collection | DOAJ |
description | Alkbh5 is one of the primary demethylases responsible for reversing N6-methyladenosine (m6A) modifications on mRNAs, and it plays a crucial role in many physiological and pathological processes. Previous studies have shown that Alkbh5 is required for maintaining the function of leukemia stem cells but is dispensable for normal hematopoiesis. In this study, we found that Alkbh5 deletion led to a moderate increase in the number of multiple progenitor cell populations while compromising the long-term self-renewal capacity of hematopoietic stem cells (HSCs). Here, we used RNA-seq and m6A-seq strategies to explore the underlying molecular mechanism. At the molecular level, Alkbh5 may regulate hematopoiesis by reducing m6A modification of Cebpa and maintaining gene expression levels. Overall, our study unveiled an essential role for Alkbh5 in regulating HSC homeostasis and provides a reference for future research in this area. |
first_indexed | 2024-03-12T15:00:32Z |
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id | doaj.art-803aef4507f44c05be115bf66e52ba07 |
institution | Directory Open Access Journal |
issn | 2391-5463 |
language | English |
last_indexed | 2024-03-12T15:00:32Z |
publishDate | 2023-08-01 |
publisher | De Gruyter |
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spelling | doaj.art-803aef4507f44c05be115bf66e52ba072023-08-14T07:06:42ZengDe GruyterOpen Medicine2391-54632023-08-0118147786.e610.1515/med-2023-0766Alkbh5 plays indispensable roles in maintaining self-renewal of hematopoietic stem cellsYang Bijie0Liu Yuanyuan1Xiao Feifei2Liu Zhilong3Chen Zhe4Li Zhigang5Zhou Chengfang6Kuang Mei7Shu Yi8Liu Shan9Zou Lin10Center for Clinical Molecular Medicine & Newborn Screening, Children’s Hospital of Chongqing Medical University, National Clinical Research Center for Child Health and Disorders, Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing Engineering Research Center of Stem Cell Therapy, 400014, Chongqing, PR ChinaInstitute of Life Sciences, Chongqing Medical University, Chongqing, ChinaDepartment of Hematology, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, ChinaDepartment of Hematology, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, ChinaInstitute of Life Sciences, Chongqing Medical University, Chongqing, ChinaInstitute of Life Sciences, Chongqing Medical University, Chongqing, ChinaInstitute of Life Sciences, Chongqing Medical University, Chongqing, ChinaDepartment of Hematology, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, ChinaCenter for Clinical Molecular Medicine & Newborn Screening, Children’s Hospital of Chongqing Medical University, National Clinical Research Center for Child Health and Disorders, Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing Engineering Research Center of Stem Cell Therapy, 400014, Chongqing, PR ChinaCenter for Clinical Molecular Medicine & Newborn Screening, Children’s Hospital of Chongqing Medical University, National Clinical Research Center for Child Health and Disorders, Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing Engineering Research Center of Stem Cell Therapy, 400014, Chongqing, PR ChinaCenter for Clinical Molecular Medicine & Newborn Screening, Children’s Hospital of Chongqing Medical University, National Clinical Research Center for Child Health and Disorders, Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing Engineering Research Center of Stem Cell Therapy, 400014, Chongqing, PR ChinaAlkbh5 is one of the primary demethylases responsible for reversing N6-methyladenosine (m6A) modifications on mRNAs, and it plays a crucial role in many physiological and pathological processes. Previous studies have shown that Alkbh5 is required for maintaining the function of leukemia stem cells but is dispensable for normal hematopoiesis. In this study, we found that Alkbh5 deletion led to a moderate increase in the number of multiple progenitor cell populations while compromising the long-term self-renewal capacity of hematopoietic stem cells (HSCs). Here, we used RNA-seq and m6A-seq strategies to explore the underlying molecular mechanism. At the molecular level, Alkbh5 may regulate hematopoiesis by reducing m6A modification of Cebpa and maintaining gene expression levels. Overall, our study unveiled an essential role for Alkbh5 in regulating HSC homeostasis and provides a reference for future research in this area.https://doi.org/10.1515/med-2023-0766hematopoietic stem cellsself-renewaldemethylation |
spellingShingle | Yang Bijie Liu Yuanyuan Xiao Feifei Liu Zhilong Chen Zhe Li Zhigang Zhou Chengfang Kuang Mei Shu Yi Liu Shan Zou Lin Alkbh5 plays indispensable roles in maintaining self-renewal of hematopoietic stem cells Open Medicine hematopoietic stem cells self-renewal demethylation |
title | Alkbh5 plays indispensable roles in maintaining self-renewal of hematopoietic stem cells |
title_full | Alkbh5 plays indispensable roles in maintaining self-renewal of hematopoietic stem cells |
title_fullStr | Alkbh5 plays indispensable roles in maintaining self-renewal of hematopoietic stem cells |
title_full_unstemmed | Alkbh5 plays indispensable roles in maintaining self-renewal of hematopoietic stem cells |
title_short | Alkbh5 plays indispensable roles in maintaining self-renewal of hematopoietic stem cells |
title_sort | alkbh5 plays indispensable roles in maintaining self renewal of hematopoietic stem cells |
topic | hematopoietic stem cells self-renewal demethylation |
url | https://doi.org/10.1515/med-2023-0766 |
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