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在维持造血干细胞自我更新方面发挥着不可或缺的作用。

plays indispensable roles in maintaining self-renewal of hematopoietic stem cells.

作者信息

Yang Bijie, Liu Yuanyuan, Xiao Feifei, Liu Zhilong, Chen Zhe, Li Zhigang, Zhou Chengfang, Kuang Mei, Shu Yi, Liu Shan, Zou Lin

机构信息

Center 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 China.

Institute of Life Sciences, Chongqing Medical University, Chongqing, China.

出版信息

Open Med (Wars). 2023 Aug 9;18(1):20230766. doi: 10.1515/med-2023-0766. eCollection 2023.

DOI:10.1515/med-2023-0766
PMID:37588656
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10426271/
Abstract

is one of the primary demethylases responsible for reversing N6-methyladenosine (mA) modifications on mRNAs, and it plays a crucial role in many physiological and pathological processes. Previous studies have shown that is required for maintaining the function of leukemia stem cells but is dispensable for normal hematopoiesis. In this study, we found that 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 mA-seq strategies to explore the underlying molecular mechanism. At the molecular level, may regulate hematopoiesis by reducing mA modification of and maintaining gene expression levels. Overall, our study unveiled an essential role for in regulating HSC homeostasis and provides a reference for future research in this area.

摘要

是负责逆转mRNA上N6-甲基腺苷(mA)修饰的主要去甲基化酶之一,并且在许多生理和病理过程中发挥关键作用。先前的研究表明,对于维持白血病干细胞的功能是必需的,但对于正常造血是可有可无的。在本研究中,我们发现缺失导致多个祖细胞群体数量适度增加,同时损害造血干细胞(HSC)的长期自我更新能力。在这里,我们使用RNA测序和mA测序策略来探索潜在的分子机制。在分子水平上,可能通过减少的mA修饰并维持基因表达水平来调节造血。总体而言,我们的研究揭示了在调节HSC稳态中的重要作用,并为该领域的未来研究提供了参考。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f0a0/10426271/773725319026/j_med-2023-0766-fig005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f0a0/10426271/57c22729775a/j_med-2023-0766-fig001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f0a0/10426271/71190eb2ec77/j_med-2023-0766-fig002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f0a0/10426271/63490547ad8e/j_med-2023-0766-fig003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f0a0/10426271/8706ddb11f14/j_med-2023-0766-fig004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f0a0/10426271/773725319026/j_med-2023-0766-fig005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f0a0/10426271/57c22729775a/j_med-2023-0766-fig001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f0a0/10426271/71190eb2ec77/j_med-2023-0766-fig002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f0a0/10426271/63490547ad8e/j_med-2023-0766-fig003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f0a0/10426271/8706ddb11f14/j_med-2023-0766-fig004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f0a0/10426271/773725319026/j_med-2023-0766-fig005.jpg

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本文引用的文献

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Cell Stem Cell. 2022 Jan 6;29(1):149-159.e7. doi: 10.1016/j.stem.2021.09.014. Epub 2021 Oct 21.
2
Chronic interleukin-1 exposure triggers selection for Cebpa-knockout multipotent hematopoietic progenitors.慢性白细胞介素-1 暴露会引发 Cebpa 基因敲除多能造血祖细胞的选择。
J Exp Med. 2021 Jun 7;218(6). doi: 10.1084/jem.20200560.
3
The mRNA m6A reader YTHDF2 suppresses proinflammatory pathways and sustains hematopoietic stem cell function.
血液系统恶性肿瘤的新视角:免疫微环境中的m6A修饰
Front Immunol. 2024 May 28;15:1374390. doi: 10.3389/fimmu.2024.1374390. eCollection 2024.
mRNA m6A 阅读器 YTHDF2 抑制促炎途径并维持造血干细胞功能。
J Exp Med. 2021 Mar 1;218(3). doi: 10.1084/jem.20200829.
4
Leukemogenic Chromatin Alterations Promote AML Leukemia Stem Cells via a KDM4C-ALKBH5-AXL Signaling Axis.致白血病染色质改变通过 KDM4C-ALKBH5-AXL 信号轴促进 AML 白血病干细胞。
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5
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Cell Stem Cell. 2020 Jul 2;27(1):64-80.e9. doi: 10.1016/j.stem.2020.04.009. Epub 2020 May 12.
6
Stage-specific requirement for Mettl3-dependent mA mRNA methylation during haematopoietic stem cell differentiation.在造血干细胞分化过程中,Mettl3 依赖性 mA mRNA 甲基化的阶段特异性要求。
Nat Cell Biol. 2019 Jun;21(6):700-709. doi: 10.1038/s41556-019-0318-1. Epub 2019 May 6.
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Cell Stem Cell. 2019 Mar 7;24(3):477-486.e6. doi: 10.1016/j.stem.2018.11.022. Epub 2019 Jan 17.
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The Biology of mA RNA Methylation in Normal and Malignant Hematopoiesis.mRNA 甲基化在正常和恶性造血中的生物学。
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