Enhanced Reconstitution of Human Erythropoiesis and Thrombopoiesis in an Immunodeficient Mouse Model with Kit(Wv) Mutations.
Enhanced Reconstitution of Human Erythropoiesis and Thrombopoiesis in an Immunodeficient Mouse Model with Kit(Wv) Mutations.
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DOI：
10.1016/j.stemcr.2016.07.002
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发表时间：
2016-09-13
影响因子：
5.9
通讯作者：
Akashi, Koichi
中科院分区：
文献类型：
--
作者：
Yurino, Ayano;Takenaka, Katsuto;Yamauchi, Takuji;Nunomura, Takuya;Uehara, Yasufumi;Jinnouchi, Fumiaki;Miyawaki, Kohta;Kikushige, Yoshikane;Kato, Koji;Miyamoto, Toshihiro;Iwasaki, Hiromi;Kunisaki, Yuya;Akashi, Koichi
在人-小鼠异种移植模型中，人造血重建通常是B淋巴主导的。在这里，我们表明，将纯合KitWv突变引入具有NOD-Sirpa（BRGS）的C57 BL/6.Rag2nullIl2rgnull小鼠中强烈促进了人类多谱系重建。在异种移植人CD 34 + CD 38 −脐带血细胞后，这些新产生的C57 BL/6. Rag 2nullIl 2 rgnullNOD-Sirpa KitWv/Wv（BRGSKWv/Wv）小鼠与BRGS小鼠相比，显示出显著更高水平的人细胞嵌合和长期多谱系重建。引人注目的是，这只小鼠显示出人类红细胞生成和血小板生成的稳健重建，骨髓中具有终末成熟。此外，通过氯膦酸盐给药消耗宿主巨噬细胞导致循环中存在人红细胞和血小板。因此，小鼠KIT信号传导的减弱极大地增强了小鼠骨髓中人造血干细胞和祖细胞（HSPC）的多谱系分化，推测是通过胜过小鼠HSPC以占据合适的微环境。BRGSKWv/Wv小鼠模型是研究人类多系造血的有用工具。小鼠中的KitWv突变（BRGSKWv/Wv）促进人类多谱系重建在BRGSKWv/Wv中重建稳健的人类红细胞生成和血小板生成在BRGSKWv/Wv中的多谱系植入不需要外源性人类细胞因子KitWv突变允许人类HSPC在骨髓小生境中胜过小鼠HSPC在这篇文章中，Akashi及其同事建立了一种具有功能丧失KitWv突变的新型小鼠品系。（BRGSKWv/Wv），其显示了在没有外源性人细胞因子的情况下人HSC的高效、长期和多谱系植入。BRGSKWv/Wv小鼠骨髓中具有终末成熟的人红细胞生成和血小板生成增强。这种新的小鼠系将有助于了解人类多谱系造血和恶性造血疾病。
In human-to-mouse xenograft models, reconstitution of human hematopoiesis is usually B-lymphoid dominant. Here we show that the introduction of homozygous KitWv mutations into C57BL/6.Rag2nullIl2rgnull mice with NOD-Sirpa (BRGS) strongly promoted human multi-lineage reconstitution. After xenotransplantation of human CD34+CD38− cord blood cells, these newly generated C57BL/6.Rag2nullIl2rgnullNOD-Sirpa KitWv/Wv (BRGSKWv/Wv) mice showed significantly higher levels of human cell chimerism and long-term multi-lineage reconstitution compared with BRGS mice. Strikingly, this mouse displayed a robust reconstitution of human erythropoiesis and thrombopoiesis with terminal maturation in the bone marrow. Furthermore, depletion of host macrophages by clodronate administration resulted in the presence of human erythrocytes and platelets in the circulation. Thus, attenuation of mouse KIT signaling greatly enhances the multi-lineage differentiation of human hematopoietic stem and progenitor cells (HSPCs) in mouse bone marrow, presumably by outcompeting mouse HSPCs to occupy suitable microenvironments. The BRGSKWv/Wv mouse model is a useful tool to study human multi-lineage hematopoiesis. KitWv mutations in mice (BRGSKWv/Wv) promote human multi-lineage reconstitution Robust human erythropoiesis and thrombopoiesis are reconstituted in BRGSKWv/Wv Exogenous human cytokine is not required for multi-lineage engraftment in BRGSKWv/Wv KitWv mutations allow human HSPCs to outcompete mouse HSPCs in bone marrow niches In this article, Akashi and colleagues established a novel mouse strain with loss-of-function KitWv mutations (BRGSKWv/Wv), which shows a highly efficient, long-term, and multi-lineage engraftment of human HSCs without exogenous human cytokines. Human erythropoiesis and thrombopoiesis with terminal maturation are enhanced in BRGSKWv/Wv mouse bone marrow. This new mouse line will help in understanding human multi-lineage hematopoiesis and malignant hematopoietic disorders.
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CD47是人类急性髓样白血病干细胞的不良预后因素和治疗抗体靶标。
影响因子：
64.5
作者：
Majeti R;Chao MP;Alizadeh AA;Pang WW;Jaiswal S;Gibbs KD Jr;van Rooijen N;Weissman IL
通讯作者：
Weissman IL
影响因子：
20.3
作者：
Hu, Zheng;Yang, Yong-Guang
通讯作者：
Yang, Yong-Guang
影响因子：
64.8
作者：
通讯作者：
--
DOI：
10.1016/j.clim.2009.12.008
发表时间：
2010-04
期刊：
Clinical immunology (Orlando, Fla.)
影响因子：
--
作者：
Brehm MA;Cuthbert A;Yang C;Miller DM;DiIorio P;Laning J;Burzenski L;Gott B;Foreman O;Kavirayani A;Herlihy M;Rossini AA;Shultz LD;Greiner DL
通讯作者：
Greiner DL
影响因子：
2.1
作者：
Ishikawa, Fumihiko
通讯作者：
Ishikawa, Fumihiko