Transcription factor GATA-2 is required for proliferation/survival of early hematopoietic cells and mast cell formation, but not for erythroid and myeloid terminal differentiation
Transcription factor GATA-2 is required for proliferation/survival of early hematopoietic cells and mast cell formation, but not for erythroid and myeloid terminal differentiation
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DOI：
10.1182/blood.v89.10.3636.3636_3636_3643
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发表时间：
1997-05-15
期刊：
影响因子：
20.3
通讯作者：
Orkin, SH
中科院分区：
文献类型：
--
作者：
Tsai, FY;Orkin, SH
锌指转录因子加塔-2在维持早期造血细胞库中起关键作用。为了确定其在造血细胞增殖、存活和分化中的特定功能，我们分析了加塔-2（-/-）细胞在体外培养系统中用于增殖和维持未定型祖细胞或分化特定谱系的造血潜能。通过胚胎干细胞的两步体外分化试验和卵黄囊细胞的体外培养，我们证明了加塔-2对于多能造血祖细胞的扩增和肥大细胞的形成是必需的，但对于红系细胞和巨噬细胞的终末分化是不可或缺的。存活的罕见的加塔-2（-/-）多能祖细胞增殖不良，并产生具有广泛细胞死亡的小集落，这意味着加塔-2可能在早期造血细胞的增殖和存活中起作用。为了探索导致加塔-2（-/-）细胞的造血缺陷的可能机制，我们杂交突变小鼠品系以评估p53缺失对加塔-2（-/-）造血细胞的行为的影响。加塔-2（-/-）/p53（-/-）化合物突变胚胎的分析显示p53的缺失部分地恢复了总加塔-2（-/-）造血细胞的数量，并因此提示加塔-2和p53通路之间的潜在联系。(C)1997年，美国血液学会。
The zinc-finger transcription factor GATA-2 plays a critical role in maintaining the pool of early hematopoietic cells. To define its specific functions in the proliferation, survival, and differentiation of hematopoietic cells, we analyzed the hematopoietic potential of GATA-2(-/-) cells in in vitro culture systems for proliferation and maintenance of uncommitted progenitors or differentiation of specific lineages. From a two-step in vitro differentiation assay of embryonic stem cells and in vitro culture of yolk sac cells, we demonstrate that GATA-2 is required for the expansion of multipotential hematopoietic progenitors and the formation of mast cells, but dispensable for the terminal differentiation of erythroid cells and macrophages. The rare GATA-2(-/-) multipotential progenitors that survive proliferate poorly and generate small colonies with extensive cell death, implying that GATA-2 may play a role in both the proliferation and survival of early hematopoietic cells. To explore possible mechanisms resulting in the hematopoietic defects of GATA-2(-/-) cells, we interbred mutant mouse strains to assess the effects of p53 loss on the behavior of GATA-2(-/-) hematopoietic cells, Analysis of GATA-2(-/-)/p53(-/-) compound-mutant embryos shows that the absence of p53 partially restores the number of total GATA-2(-/-) hematopoietic cells, and therefore suggests a potential link between GATA-2 and p53 pathways. (C) 1997 by The American Society of Hematology.