Overexpression of Short Variant Form of New Kelch Family Protein Leads to Erythroid and Megakaryocyte Dysplasia by Targeting Megakaryocyte-Erythroid Progenitors.
Overexpression of Short Variant Form of New Kelch Family Protein Leads to Erythroid and Megakaryocyte Dysplasia by Targeting Megakaryocyte-Erythroid Progenitors.
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新 Kelch 家族蛋白短变体的过度表达通过靶向巨核细胞-红系祖细胞导致红系和巨核细胞发育不良
DOI：
10.1089/dna.2018.4206
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发表时间：
2018-10
影响因子：
3.1
通讯作者：
Zhang Xiangzhong
中科院分区：
文献类型：
--
作者：
Lin Yansi;Luo Yuxuan;Hu Fangxiao;Wang Tongjie;Dong Yong;Yang Dan;He Xiaodan;Chen Xiaoli;Wang Jinyong;Du Juan;Zhang Xiangzhong
Nd 1-S是Nd 1（Ivns 1abp）的核定位短变体形式，编码Kelch家族转录因子。虽然已在转移和阿霉素诱导的心脏毒性的背景下研究了Nd 1的功能，但对其在造血中的作用知之甚少。本研究通过将过量表达Nd 1-S的小鼠造血干细胞和祖细胞（HSPCs）移植到受体小鼠（Nd 1-S小鼠）体内，研究Nd 1-S在造血中的作用。Nd 1-S的增强表达导致红细胞和巨核细胞发育不良，表现为Nd 1-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（MEP）积累在这些Nd 1-S小鼠异常形态和缺陷的集落形成能力。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，我们的研究提供了从头证据表明，在HSPCs中的Nd 1-S过表达通过靶向MEP导致体内红系和巨核细胞发育不良。
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.
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发表时间：
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