MEIS2 regulates endothelial to hematopoietic transition of human embryonic stem cells by targeting TAL1
MEIS2 regulates endothelial to hematopoietic transition of human embryonic stem cells by targeting TAL1
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MEIS2通过靶向TAL1调节人胚胎干细胞的内皮向造血转化
DOI：
10.1186/s13287-018-1074-z
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发表时间：
2018-12-07
影响因子：
7.5
通讯作者：
Zhou, Jiaxi
中科院分区：
文献类型：
--
作者：
Wang, Mengge;Wang, Hongtao;Zhou, Jiaxi
背景尽管在造血分化方法的开发方面取得了相当大的进展，但从人胚胎干细胞（hESC）有效产生可移植造血干细胞（HSC）和其他真正的功能性血细胞仍然不成功。因此，更好地了解造血分化的hESC的分子机制是高度required.MethodsIn这项研究中，通过使用全基因组基因分析，我们确定髓系异位病毒整合位点2同源物（MEIS 2）作为一个潜在的调节人胚胎干细胞早期造血分化。我们利用CRISPR/CAS9技术将MEIS 2基因缺失hESCs，并诱导其向造血细胞分化，向巨核细胞分化。此外，MEIS 2缺失抑制生血内皮特化和内皮向造血转变（EHT），导致造血分化受损。在机制上，TAL 1作为下游基因在早期造血过程中介导MEIS 2的功能。有趣的是，不同于MEIS 1，MEIS 2删除发挥巨核细胞分化和血小板生成hESCs.ConclusionsOur研究结果的影响最小，推进人类造血发育的理解，并可能提供新的见解，为大规模产生的功能性血细胞的临床应用。
BackgroundDespite considerable progress in the development of methods for hematopoietic differentiation, efficient generation of transplantable hematopoietic stem cells (HSCs) and other genuine functional blood cells from human embryonic stem cells (hESCs) is still unsuccessful. Therefore, a better understanding of the molecular mechanism underlying hematopoietic differentiation of hESCs is highly demanded.MethodsIn this study, by using whole-genome gene profiling, we identified Myeloid Ectopic Viral Integration Site 2 homolog (MEIS2) as a potential regulator of hESC early hematopoietic differentiation. We deleted MEIS2 gene in hESCs using the CRISPR/CAS9 technology and induced them to hematopoietic differentiation, megakaryocytic differentiation.ResultsIn this study, we found that MEIS2 deletion impairs early hematopoietic differentiation from hESCs. Furthermore, MEIS2 deletion suppresses hemogenic endothelial specification and endothelial to hematopoietic transition (EHT), leading to the impairment of hematopoietic differentiation. Mechanistically, TAL1 acts as a downstream gene mediating the function of MEIS2 during early hematopoiesis. Interestingly, unlike MEIS1, MEIS2 deletion exerts minimal effects on megakaryocytic differentiation and platelet generation from hESCs.ConclusionsOur findings advance the understanding of human hematopoietic development and may provide new insights for large-scale generation of functional blood cells for clinical applications.