Haematopoietic Stem Cell Laboratory, Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, University of Oxford, Oxford, United Kingdom.
Blood. 2011 Aug 4;118(5):1291-3. doi: 10.1182/blood-2011-02-338046. Epub 2011 Jun 13.
GATA3 has been identified as a master regulator of T helper cells, as well as being important for early thymic progenitors and T-cell commitment. However, Gata3 expression initiates already at the hematopoietic stem cell (HSC) level, implicating a potential role also in the regulation of HSCs. Herein we used a conditional Gata3 knockout strategy in which Gata3 expression was completely deleted from the earliest stage of embryonic hematopoietic development after emergence of HSCs from hemogenic endothelium. Through a detailed analysis of HSCs at the phenotypic and functional level, we demonstrate that steady-state levels of HSCs are normal in Gata3(fl/fl)Vav-Cre(tg/+) mice. Moreover, through long-term primary and secondary transplantation experiments, we also unequivocally demonstrate that Gata3 has a redundant role in post-transplantation HSC self-renewal.
GATA3 已被确定为辅助性 T 细胞的主要调节因子，对于早期胸腺祖细胞和 T 细胞的定向分化也很重要。然而，Gata3 的表达在造血干细胞（HSC）水平就已经开始，这意味着它也可能在 HSC 的调节中发挥作用。在此，我们使用了一种条件性 Gata3 敲除策略，该策略在 HSCs 从造血内皮细胞中出现后，从胚胎造血发育的最早阶段就完全消除了 Gata3 的表达。通过对 HSCs 在表型和功能水平上的详细分析，我们证明 Gata3(fl/fl)Vav-Cre(tg/+) 小鼠的 HSCs 处于稳态水平是正常的。此外，通过长期的原发性和继发性移植实验，我们也明确证明 Gata3 在移植后 HSC 自我更新中具有冗余作用。
