Sakai Eiko, Kitajima Kenji, Sato Ayuko, Nakano Toru
Department of Pathology, School of Medicine and Frontier Biosciences, Osaka University, Yamadaok, Osaka, Japan.
Exp Hematol. 2009 Mar;37(3):334-45. doi: 10.1016/j.exphem.2008.11.007.
Runx1 is essential for both the establishment of hematopoiesis during development and maintenance of adult hematopoiesis. To reveal the roles of Runx1, we examined how and when Runx1 functions during development of hematopoiesis, and revealed the genes controlled by Runx1.
A combined in vitro approach involving in vitro hematopoietic differentiation of embryonic stem cells and conditional gene expression of Runx1 was utilized for this study. Then we analyzed the effects of Runx1 on the differentiation and proliferation of hematopoietic cells and carried out DNA microarray analysis.
Pulse expression of Runx1 prior to the emergence of hematopoietic cells caused immature hematopoietic cell increase but did not have any effects on the induction of hemogenic cells. During this process, the mRNA level of several endothelial cell-specific genes was downregulated.
Runx1 expression play important roles on the proliferation of emerging immature hematopoietic progenitors or the transition process from endothelial to hematopoietic cells presumably by suppressing the genes related to endothelial phenotype.
Runx1对于发育过程中造血作用的建立以及成体造血作用的维持均至关重要。为揭示Runx1的作用，我们研究了Runx1在造血作用发育过程中的作用方式及时间，并揭示了受Runx1调控的基因。
本研究采用了一种体外联合方法，包括胚胎干细胞的体外造血分化和Runx1的条件性基因表达。然后我们分析了Runx1对造血细胞分化和增殖的影响，并进行了DNA微阵列分析。
在造血细胞出现之前Runx1的脉冲式表达导致未成熟造血细胞增加，但对造血细胞的诱导没有任何影响。在此过程中，几个内皮细胞特异性基因的mRNA水平下调。
Runx1的表达可能通过抑制与内皮表型相关的基因，对新出现的未成熟造血祖细胞的增殖或从内皮细胞到造血细胞的转变过程发挥重要作用。
