Regulation of RUNX1 dosage is crucial for efficient blood formation from hemogenic endothelium.
Regulation of RUNX1 dosage is crucial for efficient blood formation from hemogenic endothelium.
复制标题
RUNX1剂量的调节对于造血内皮的有效血液形成至关重要。
DOI：
10.1242/dev.149419
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发表时间：
2018-03-12
期刊：
影响因子：
--
通讯作者：
Lacaud G
中科院分区：
文献类型：
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作者：
Lie-A-Ling M;Marinopoulou E;Lilly AJ;Challinor M;Patel R;Lancrin C;Kouskoff V;Lacaud G
在个体发育过程中，造血干细胞和祖细胞通过严格依赖于转录因子RUNX1的内皮到造血细胞的转变从血源性内皮分化而来。尽管众所周知，RUNX1在造血的启动中是必不可少的，但对于RUNX1的剂量在血管内皮细胞和内皮细胞向造血细胞转化过程中的作用知之甚少。在这里，我们使用小鼠胚胎干细胞分化系统来确定RUNX1剂量是否以及如何影响血源性内皮分化。使用可诱导的RUNX1表达结合RUNX1辅助因子CBFβ的表达变化，使我们能够评估广泛的RUNX1水平。我们证明，低水平的RUNX1对于启动有效的内皮向造血细胞的转变是充分和必要的。随后，RUNX1也需要完成内皮到造血细胞的转变，并产生有功能的造血祖细胞。相比之下，RUNX1水平的升高能够推动加速的内皮向造血细胞的转变，但由此产生的细胞无法产生成熟的造血细胞。综上所述，我们的结果表明RUNX1的剂量在血源性内皮成熟和造血系统的建立中起着关键作用。摘要：在造血开始时，调节RUNX1的剂量对于血源性内皮的成功成熟以及内皮向造血细胞转化的启动和完成都是至关重要的。
During ontogeny, hematopoietic stem and progenitor cells arise from hemogenic endothelium through an endothelial-to-hematopoietic transition that is strictly dependent on the transcription factor RUNX1. Although it is well established that RUNX1 is essential for the onset of hematopoiesis, little is known about the role of RUNX1 dosage specifically in hemogenic endothelium and during the endothelial-to-hematopoietic transition. Here, we used the mouse embryonic stem cell differentiation system to determine if and how RUNX1 dosage affects hemogenic endothelium differentiation. The use of inducible Runx1 expression combined with alterations in the expression of the RUNX1 co-factor CBFβ allowed us to evaluate a wide range of RUNX1 levels. We demonstrate that low RUNX1 levels are sufficient and necessary to initiate an effective endothelial-to-hematopoietic transition. Subsequently, RUNX1 is also required to complete the endothelial-to-hematopoietic transition and to generate functional hematopoietic precursors. In contrast, elevated levels of RUNX1 are able to drive an accelerated endothelial-to-hematopoietic transition, but the resulting cells are unable to generate mature hematopoietic cells. Together, our results suggest that RUNX1 dosage plays a pivotal role in hemogenic endothelium maturation and the establishment of the hematopoietic system. Summary: At the onset of hematopoiesis, regulation of RUNX1 dosage is crucial for the successful maturation of hemogenic endothelium and for both the initiation and completion of the endothelial-to-hematopoietic transition.
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影响因子：
11.8
作者：
Goode DK;Obier N;Vijayabaskar MS;Lie-A-Ling M;Lilly AJ;Hannah R;Lichtinger M;Batta K;Florkowska M;Patel R;Challinor M;Wallace K;Gilmour J;Assi SA;Cauchy P;Hoogenkamp M;Westhead DR;Lacaud G;Kouskoff V;Göttgens B;Bonifer C
通讯作者：
Bonifer C
影响因子：
64.8
作者：
Chen, Michael J.;Yokomizo, Tomomasa;Zeigler, Brandon M.;Dzierzak, Elaine;Speck, Nancy A.
通讯作者：
Speck, Nancy A.
影响因子：
3.7
作者：
Bartman, Colleen M.;Egelston, Jennifer;Ren, Xiaojun;Das, Raibatak;Phiel, Christopher J.
通讯作者：
Phiel, Christopher J.
影响因子：
5.4
作者：
Dull, T;Zufferey, R;Naldini, L
通讯作者：
Naldini, L
影响因子：
21.3
作者：
通讯作者：
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