Runt-related transcription factor 1 (RUNX1) is required for definitive hematopoiesis; however, the functions of most human RUNX1 isoforms are unclear. In particular, the effects of RUNX1-205 (a novel splice variant that lacks exon 6 in comparison with RUNX1b) on human hematopoiesis are not clear. In this study, a human embryonic stem cell (hESC) line with inducible RUNX1-205 overexpression was established. Analyses of these cells revealed that induction of RUNX1-205 overexpression at early stage did not influence the induction of mesoderm but blocked the emergence of CD34⁺ cells, and the production of hematopoietic stem/progenitor cells was significantly reduced. In addition, the expression of hematopoiesis-related factors was downregulated. However, these effects were abolished when RUNX1-205 overexpression was induced after Day 6 in co-cultures of hESCs and AGM-S3 cells, indicating that the inhibitory effect occurred prior to generation of hemogenic endothelial cells, while the promotive effect could be observed during the late stage of hematopoiesis. This is very similar to that of RUNX1b. Interestingly, the mRNA expression profile of RUNX1-205 during hematopoiesis was distinct from that of RUNX1b, and the protein stability of RUNX1-205 was much higher than that of RUNX1b. Thus, the function of RUNX1-205 in normal and diseased models should be further explored.

中文翻译：

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RUNX1-205是人RUNX1基因的新型剪接变体，在造血后期对中胚层-造血转变具有阻断作用和促进作用。

Runt 相关转录因子 1 ( RUNX1 ) 是确定造血所必需的；然而，大多数人类RUNX1亚型的功能尚不清楚。特别是，RUNX1-205（一种与RUNX1b相比缺少外显子 6 的新型剪接变体）对人类造血功能的影响尚不清楚。在这项研究中，建立了具有可诱导RUNX1-205过表达的人类胚胎干细胞 (hESC) 系。对这些细胞的分析表明，早期诱导RUNX1-205过表达不影响中胚层的诱导，但阻止了 CD34 ⁺细胞，并且造血干/祖细胞的产生显着减少。此外，造血相关因子的表达被下调。然而，当RUNX1-205在 hESCs 和 AGM-S3 细胞的共培养物中诱导第 6天后过表达时，这些作用被消除，表明抑制作用发生在造血内皮细胞产生之前，而促进作用可以在造血后期。这与RUNX1b非常相似。有趣的是，RUNX1-205在造血过程中的 mRNA 表达谱与RUNX1b不同，并且RUNX1-205的蛋白质稳定性远高于 RUNX1b。因此，函数应该进一步探索正常和患病模型中的RUNX1 - 205。