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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >E2a Proteins Maintain The Hematopoietic Stem Cell Pool And Promote The Maturation Of Myelolymphoid And Mveloervthroid Progenitors
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E2a Proteins Maintain The Hematopoietic Stem Cell Pool And Promote The Maturation Of Myelolymphoid And Mveloervthroid Progenitors

机译：E2a蛋白维持造血干细胞池并促进骨髓和类胡萝卜素祖细胞的成熟

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摘要

Hematopoiesis is a tightly controlled process maintained by a small pool of hematopoietic stem cells (HSCs). Here, we demonstrate that the LT-HSC, MPP, premegakaryocytic/erythroid, Pre CFU-E, Pre GM, MkP, and granulocyte-macrophage compartments were all significantly reduced in E2A-deficient bone marrow. Despite a severe depletion of erythroid progenitors, the erythrocyte and megakaryocyte compartments were equivalent in E2A-deficient bone marrow as compared with wild-type mice. E2A-def icient HSCs also failed to efficiently maintain the HSC pool on serial transplantation, and we demonstrate that the E2A proteins regulate cell cycle progression of HSCs by regulating the expression of p21c'P1, p27_kiP1 and the thrombopoietin receptor, known regulators of HSC self-renewal activity. Based on these observations, we propose that the E2A proteins promote the developmental progression of the entire spectrum of early hematopoietic progenitors and to suppress an erythroid specific program of gene expression in alternative cell lineages. Last, the data mechanistically link E2A, cell cycle regulators, and the maintenance of the HSC pool in a common pathway.
机译：造血是一个由少量造血干细胞（HSC）维持的严格控制的过程。在这里，我们证明LT-HSC，MPP，前巨核细胞/类红细胞，Pre CFU-E，Pre GM，MkP和粒细胞巨噬细胞区室在E2A缺陷型骨髓中均显着减少。尽管严重消耗了红系祖细胞，但与野生型小鼠相比，E2A缺陷型骨髓中的红细胞和巨核细胞区室是相同的。缺乏E2A的HSC在连续移植时也未能有效维持HSC池，我们证明E2A蛋白通过调节p21c'P1，p27_kiP1和血小板生成素受体（已知的HSC自身调节剂）的表达来调节HSC的细胞周期进程-更新活动。基于这些观察结果，我们建议E2A蛋白促进早期造血祖细胞的整个谱的发展进程，并抑制替代细胞谱系中的红系特定基因表达程序。最后，数据将E2A，细胞周期调节剂和HSC池的维护以机械方式联系在一起。

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