Long-term cultured E2A-deficient hematopoietic progenitor cells are pluripotent
Long-term cultured E2A-deficient hematopoietic progenitor cells are pluripotent
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DOI：
10.1016/s1074-7613(04)00049-4
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发表时间：
2004-03-01
期刊：
影响因子：
32.4
通讯作者：
Murre, C
中科院分区：
文献类型：
--
作者：
Ikawa, T;Kawamoto, H;Murre, C
E2A蛋白对于祖细胞阶段以外的B细胞的发展至关重要。在这里，我们具有分离的E2A缺陷骨髓来源的细胞，它们具有长期在体外和同时表达的能力，在低水平，不同的造血细胞谱系的调节剂。当转移到致命的辐照宿主中时，E2A缺陷型造血祖细胞会重建T，NK，髓样，树突状和红细胞性谱系，但未能发展为成熟的B谱系细胞。 E47在E2A缺陷型造血祖细胞中的强化表达直接激活B谱系特异性基因的子集的转录，包括Lambda5，MB-1和PAX5。相反，E47抑制了其他造血谱系的调节剂，包括TCF-1和GATA-1。这些观察结果表明，在长期培养后，E2A缺陷型造血祖细胞仍然多能，并且E2A蛋白在B细胞承诺中起关键作用。
E2A proteins are essential for the development of B cells beyond the progenitor cell stage. Here we have isolated E2A-deficient bone marrow-derived cells that have the ability to grow long-term in vitro and coexpress, at low levels, regulators of different hematopoietic cell lineages. When transferred into lethally irradiated hosts, E2A-deficient hematopoietic progenitor cells reconstitute the T, NK, myeloid, dendritic, and erythroid lineages but fail to develop into mature B lineage cells. Enforced expression of E47 in E2A-deficient hematopoietic progenitor cells directly activates the transcription of a subset of B lineage-specific genes, including lambda5, mb-1, and Pax5. In contrast, E47 inhibits the expression of regulators of other hematopoietic lineages, including TCF-1 and GATA-1. These observations indicate that E2A-deficient hematopoietic progenitor cells remain pluripotent after long-term culture in vitro and that E2A proteins play a critical role in B cell commitment.