Cañete Ana, Carmona Rita, Ariza Laura, Sánchez María José, Rojas Anabel, Muñoz-Chápuli Ramón
Department of Animal Biology, University of Málaga, Spain.
Andalusian Center for Nanomedicine and Biotechnology (BIONAND), Málaga, Spain.
Haematologica. 2017 Apr;102(4):647-655. doi: 10.3324/haematol.2016.155812. Epub 2017 Jan 5.
GATA transcription factors are expressed in the mesoderm and endoderm during development. GATA1-3, but not GATA4, are critically involved in hematopoiesis. An enhancer (G2) of the mouse gene directs its expression throughout the lateral mesoderm and the allantois, beginning at embryonic day 7.5, becoming restricted to the septum transversum by embryonic day 10.5, and disappearing by midgestation. We have studied the developmental fate of the G2-Gata4 cell lineage using a G2-Gata4;R26R mouse line. We found a substantial number of YFP hematopoietic cells of lymphoid, myeloid and erythroid lineages in embryos. Fetal CD41/cKit/CD34 and Lin/cKit/CD31 YFP hematopoietic progenitors were much more abundant in the placenta than in the aorta-gonad-mesonephros area. They were clonogenic in the MethoCult assay and fully reconstituted hematopoiesis in myeloablated mice. YFP cells represented about 20% of the hematopoietic system of adult mice. Adult YFP hematopoietic stem cells constituted a long-term repopulating, transplantable population. Thus, a lineage of adult hematopoietic stem cells is characterized by the expression of GATA4 in their embryonic progenitors and probably by its extraembryonic (placental) origin, although GATA4 appeared not to be required for hematopoietic stem cell differentiation. Both lineages basically showed similar physiological behavior in normal mice, but clinically relevant properties of this particular hematopoietic stem cell population should be checked in physiopathological conditions.
GATA转录因子在发育过程中表达于中胚层和内胚层。GATA1 - 3而非GATA4在造血过程中起关键作用。小鼠基因的一个增强子（G2）在胚胎第7.5天开始引导其在整个侧中胚层和尿囊表达，到胚胎第10.5天局限于横隔，在妊娠中期消失。我们使用G2 - Gata4;R26R小鼠品系研究了G2 - Gata4细胞谱系的发育命运。我们在胚胎中发现了大量淋巴系、髓系和红系谱系的YFP造血细胞。胎儿CD41/cKit/CD34和Lin/cKit/CD31 YFP造血祖细胞在胎盘中比在主动脉 - 性腺 - 中肾区域丰富得多。它们在甲基纤维素培养试验中具有克隆形成能力，并且能在经骨髓清除的小鼠中完全重建造血功能。YFP细胞占成年小鼠造血系统的约20%。成年YFP造血干细胞构成了一个长期重建、可移植的群体。因此，成年造血干细胞的一个谱系的特征是其胚胎祖细胞中GATA4的表达以及可能的胚外（胎盘）起源，尽管GATA4似乎不是造血干细胞分化所必需的。在正常小鼠中，这两个谱系基本表现出相似的生理行为，但在生理病理条件下应检查这一特定造血干细胞群体的临床相关特性。
