Spi-B can functionally replace PU.1 in myeloid but not lymphoid development
Spi-B can functionally replace PU.1 in myeloid but not lymphoid development
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DOI：
10.1093/emboj/21.9.2220
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发表时间：
2002-05-01
期刊：
影响因子：
11.4
通讯作者：
Simon, MC
中科院分区：
文献类型：
--
作者：
Dahl, R;Ramirez-Bergeron, DL;Simon, MC
成熟的巨噬细胞、中性粒细胞和淋巴细胞在PU.1（-/-）小鼠中不发育。相反，缺乏高度相关蛋白Spi-B的小鼠产生所有造血谱系，但显示B细胞受体信号传导缺陷。这些不同的表型可能是由于PU.1和Spi-B之间的功能差异或其独特的时间和组织特异性表达（PU.1：骨髓和B细胞; Spi-B：仅B细胞）。为了解决这个问题，我们引入了Spi-B的cDNA到小鼠PU.1基因座的同源重组。在不存在PU.1的情况下，当通过胚胎干细胞的体外分化测定时，Spi-B拯救了巨噬细胞和粒细胞的发育。在PU. 1（Spi-B/Spi-B）拟胚体中检测到具有吞噬作用的粘附CD 11b（+）/F4/80（+）细胞，在造血祖细胞测定中存在髓样集落。尽管它能够挽救骨髓分化，但在RAG-2（-/-）互补测定中，Spi-B不能挽救淋巴发育。这些结果证明了PU.1和Spi-B之间的重要差异。这些Ets因子的仔细比较将描绘参与淋巴细胞谱系定型和/或成熟的PU.1的重要功能域。
Mature macrophages, neutrophils and lymphoid cells do not develop in PU.1(-/-) mice. In contrast, mice lacking the highly related protein Spi-B generate all hematopoietic lineages but display a B-cell receptor signaling defect. These distinct phenotypes could result from functional differences between PU.1 and Spi-B or their unique temporal and tissue-specific expression (PU.1: myeloid and B cells; Spi-B: B cells only). To address this question, we introduced the Spi-B cDNA into the murine PU.1 locus by homologous recombination. In the absence of PU.1, Spi-B rescued macrophage and granulocyte development when assayed by in vitro differentiation of embryonic stem cells. Adherent, CD11b(+)/F4/80(+) cells capable of phagocytosis were detected in PU.1(Spi-B/Spi-B) embryoid bodies, and myeloid colonies were present in hematopoietic progenitor assays. Despite its ability to rescue myeloid differentiation, Spi-B did not rescue lymphoid development in a RAG-2(-/-) complementation assay. These results demonstrate an important difference between PU.1 and Spi-B. Careful comparison of these Ets factors will delineate important functional domains of PU.1 involved in lymphocyte lineage commitment and/or maturation.