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Overexpression of Short Variant Form of New Kelch Family Protein Leads to Erythroid and Megakaryocyte Dysplasia by Targeting Megakaryocyte-Erythroid Progenitors

机译:通过靶向Megakaryocyte-eryThroid祖细胞血管血管血管血管血管血管血管血管血管血管血管血管血管血管剂的过度变异形式

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摘要

Nd1-S is the nuclear-localizing short variant form of Nd1 (Ivns1abp) encoding a Kelch family transcription factor. While the function of Nd1 has been investigated in the context of metastasis and doxorubicin-induced cardiotoxicity, little is known about its role in hematopoiesis. In this study, we investigated the function of Nd1-S in hematopoiesis by transplanting the Nd1-S-overexpressing murine hematopoietic stem and progenitor cells (HSPCs) into recipient mice (Nd1-S mice). Enforced expression of Nd1-S led to erythroid and megakaryocyte dysplasia, demonstrated by dramatically decreased red blood cells and platelets, and megakaryocytes in the peripheral blood and bone marrow of the Nd1-S mice. Moreover, phenotypic megakaryocyte-erythroid progenitors (MEPs) accumulated in these Nd1-S mice with aberrant morphology and defective colony-forming capability. Furthermore, these phenotypic MEPs showed impaired pathways regulating erythroid differentiation and megakaryocyte development. Therefore, our study provides de novo evidence that overexpression of Nd1-S in HSPCs leads to erythroid and megakaryocyte dysplasia in vivo by targeting MEPs.
机译:Nd1-S是编码Kelch家族转录因子的Nd1(Ivns1abp)的核定位短变体。虽然Nd1的功能已在转移和阿霉素诱导的心脏毒性方面得到研究,但对其在造血中的作用知之甚少。在本研究中,我们通过将Nd1-S过度表达的小鼠造血干细胞和祖细胞(HSPC)移植到受体小鼠(Nd1-S小鼠)中,研究了Nd1-S在造血中的功能。Nd1-S的强制表达导致红系和巨核细胞发育不良,表现为Nd1-S小鼠外周血和骨髓中的红细胞和血小板以及巨核细胞显著减少。此外,表型巨核细胞红系祖细胞(MEPs)在这些形态异常和集落形成能力缺陷的Nd1-S小鼠中积累。此外,这些表型MEP显示调节红系分化和巨核细胞发育的途径受损。因此,我们的研究提供了新的证据,证明Nd1-S在HSPC中的过度表达通过靶向MEP在体内导致红系和巨核细胞发育不良。

著录项

  • 来源
    《DNA and Cell Biology》 |2018年第10期|共8页
  • 作者单位

    Sun Yat Sen Univ Affiliated Hosp 3 Dept Hematol Guangzhou 510630 Guangdong Peoples R China;

    Sun Yat Sen Univ Affiliated Hosp 3 Dept Hematol Guangzhou 510630 Guangdong Peoples R China;

    Guangzhou Med Univ Chinese Acad Sci Guangzhou Inst Biomed &

    Hlth Joint Sch Life Sci Guangzhou 510530 Guangdong Peoples R China;

    Guangzhou Med Univ Chinese Acad Sci Guangzhou Inst Biomed &

    Hlth Joint Sch Life Sci Guangzhou 510530 Guangdong Peoples R China;

    Guangzhou Med Univ Chinese Acad Sci Guangzhou Inst Biomed &

    Hlth Joint Sch Life Sci Guangzhou 510530 Guangdong Peoples R China;

    Guangzhou Med Univ Chinese Acad Sci Guangzhou Inst Biomed &

    Hlth Joint Sch Life Sci Guangzhou 510530 Guangdong Peoples R China;

    Guangzhou Med Univ Chinese Acad Sci Guangzhou Inst Biomed &

    Hlth Joint Sch Life Sci Guangzhou 510530 Guangdong Peoples R China;

    Guangzhou Med Univ Chinese Acad Sci Guangzhou Inst Biomed &

    Hlth Joint Sch Life Sci Guangzhou 510530 Guangdong Peoples R China;

    Guangzhou Med Univ Chinese Acad Sci Guangzhou Inst Biomed &

    Hlth Joint Sch Life Sci Guangzhou 510530 Guangdong Peoples R China;

    Guangzhou Med Univ Chinese Acad Sci Guangzhou Inst Biomed &

    Hlth Joint Sch Life Sci Guangzhou 510530 Guangdong Peoples R China;

    Sun Yat Sen Univ Affiliated Hosp 3 Dept Hematol Guangzhou 510630 Guangdong Peoples R China;

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  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类 细胞遗传学;
  • 关键词

    Nd1; overexpression; erythroid dysplasia; megakaryocyte dysplasia; transplantation;

    机译:ND1;过度表达;红细胞发育不良;巨核细胞发育不良;移植;

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