Unipotent Megakaryopoietic Pathway Bridging Hematopoietic Stem Cells and Mature Megakaryocytes.
Unipotent Megakaryopoietic Pathway Bridging Hematopoietic Stem Cells and Mature Megakaryocytes.
复制标题
DOI：
10.1002/stem.1985
复制
发表时间：
2015-07
期刊：
影响因子：
--
通讯作者：
Chiba S
中科院分区：
文献类型：
--
作者：
Nishikii H;Kanazawa Y;Umemoto T;Goltsev Y;Matsuzaki Y;Matsushita K;Yamato M;Nolan GP;Negrin R;Chiba S
最近对血小板/巨核细胞偏向的造血干/再生细胞的鉴定需要修改巨核细胞生成的中间途径。在这里，我们展示了绕过双能巨核细胞/红系祖细胞（biEMP）的单能巨核细胞生成途径。通过培养和移植，通过 CD42b (GPIbα) 标记从小鼠骨髓中纯化的细胞被证明是单能巨核细胞祖细胞 (MKP)。 Sca1+cKit+ (LSK) 谱系 (subCD41+LSK) 中新鲜分离的 CD41+ 细胞亚群在培养中仅分化为 MKP 和成熟巨核细胞。尽管 CD41+LSK 细胞作为一个整体能够在体内分化为所有骨髓细胞和淋巴样细胞，但它们在体外和体内产生单能 MKP、成熟巨核细胞和血小板的效率比 Flt3+CD41−LSK 细胞高得多，特别是在移植后的早期阶段。在单细胞聚合酶链反应和血小板生成素 (TPO) 信号分析中，MKP 和 CD41+LSK 的一部分（但 biEMP 除外）显示出 mRNA 表达谱和可见的 TPO 介导的磷酸化的相似性。由于5-FU治疗后血小板生成的需求增加，部分CD41+LSK群体表面表达CD42b，其中90%在单细胞培养中表现出单能巨核细胞生成能力，并在移植后早期在体内主要生成血小板。这些结果表明CD41+CD42b+LSK是巨核细胞/血小板偏向干细胞/再生细胞的直接后代，但不是biEMP的后代。因此，我们展示了一种将干细胞/再生细胞和成熟巨核细胞互连的单能/高度偏向的巨核生成途径，该途径可能发挥生理作用，尤其是在紧急巨核生成中。
Recent identification of platelet/megakaryocyte-biased hematopoietic stem/repopulating cells requires revision of the intermediate pathway for megakaryopoiesis. Here, we show a unipotent megakaryopoietic pathway bypassing the bipotent megakaryocyte/erythroid progenitors (biEMPs). Cells purified from mouse bone marrow by CD42b (GPIbα) marking were demon-strated to be unipotent megakaryocytic progenitors (MKPs) by culture and transplantation. A subpopulation of freshly isolated CD41+ cells in the lineage Sca1+cKit+ (LSK) fraction (subCD41+LSK) differentiated only into MKP and mature megakaryocytes in culture. Although CD41+LSK cells as a whole were capable of differentiating into all myeloid and lymphoid cells in vivo, they produced unipotent MKP, mature megakaryocytes, and platelets in vitro and in vivo much more efficiently than Flt3+CD41−LSK cells, especially at the early phase after trans-plantation. In single cell polymerase chain reaction and thrombopoietin (TPO) signaling analyses, the MKP and a fraction of CD41+LSK, but not the biEMP, showed the similarities in mRNA expression profile and visible TPO-mediated phosphorylation. On increased demand of platelet production after 5-FU treatment, a part of CD41+LSK population expressed CD42b on the surface, and 90% of them showed unipotent megakaryopoietic capacity in single cell culture and predominantly produced platelets in vivo at the early phase after transplantation. These results suggest that the CD41+CD42b+LSK are straightforward progenies of megakaryocytes/platelet-biased stem/repopulating cells, but not progenies of biEMP. Consequently, we show a unipotent/highly biased megakaryopoietic pathway interconnecting stem/repopulating cells and mature megakaryocytes, the one that may play physiologic roles especially in emergency mega-karyopoiesis.
登录
查看更多内容
影响因子：
64.5
作者：
Kiel, MJ;Yilmaz, ÖH;Morrison, SJ
通讯作者：
Morrison, SJ
DOI：
10.1073/pnas.95.3.1195
发表时间：
1998-02-03
影响因子：
11.1
作者：
Kimura, S;Roberts, AW;Alexander, WS
通讯作者：
Alexander, WS
影响因子：
64.5
作者：
Wilson, Anne;Laurenti, Elisa;Trumpp, Andreas
通讯作者：
Trumpp, Andreas
影响因子：
64.5
作者：
Adolfsson, J;Månsson, R;Jacobsen, SEW
通讯作者：
Jacobsen, SEW
金属蛋白酶调节可改善小鼠胚胎干细胞的体外产生有效的血小板。
影响因子：
15.3
作者：
Nishikii, Hidekazu;Eto, Koji;Tamura, Noriko;Hattori, Koichi;Heissig, Beate;Kanaji, Taisuke;Sawaguchi, Akira;Goto, Shinya;Ware, Jerry;Nakauchi, Hiromitsu
通讯作者：
Nakauchi, Hiromitsu