Title |
GATA2−/− human ESCs undergo attenuated endothelial to hematopoietic transition and thereafter granulocyte commitment
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Published in |
Cell Regeneration, August 2015
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DOI | 10.1186/s13619-015-0018-7 |
Pubmed ID | |
Authors |
Ke Huang, Juan Du, Ning Ma, Jiajun Liu, Pengfei Wu, Xiaoya Dong, Minghui Meng, Wenqian Wang, Xin Chen, Xi Shi, Qianyu Chen, Zhongzhou Yang, Shubin Chen, Jian Zhang, Yuhang Li, Wei Li, Yi Zheng, Jinglei Cai, Peng Li, Xiaofang Sun, Jinyong Wang, Duanqing Pei, Guangjin Pan |
Abstract |
Hematopoiesis is a progressive process collectively controlled by an elaborate network of transcription factors (TFs). Among these TFs, GATA2 has been implicated to be critical for regulating multiple steps of hematopoiesis in mouse models. However, whether similar function of GATA2 is conserved in human hematopoiesis, especially during early embryonic development stage, is largely unknown. To examine the role of GATA2 in human background, we generated homozygous GATA2 knockout human embryonic stem cells (GATA2 (-/-) hESCs) and analyzed their blood differentiation potential. Our results demonstrated that GATA2 (-/-) hESCs displayed attenuated generation of CD34(+)CD43(+) hematopoietic progenitor cells (HPCs), due to the impairment of endothelial to hematopoietic transition (EHT). Interestingly, GATA2 (-/-) hESCs retained the potential to generate erythroblasts and macrophages, but never granulocytes. We further identified that SPI1 downregulation was partially responsible for the defects of GATA2 (-/-) hESCs in generation of CD34(+)CD43(+) HPCs and granulocytes. Furthermore, we found that GATA2 (-/-) hESCs restored the granulocyte potential in the presence of Notch signaling. Our findings revealed the essential roles of GATA2 in EHT and granulocyte development through regulating SPI1, and uncovered a role of Notch signaling in granulocyte generation during hematopoiesis modeled by human ESCs. |
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Unknown | 1 | 100% |
Demographic breakdown
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Members of the public | 1 | 100% |
Mendeley readers
Geographical breakdown
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Japan | 1 | 3% |
Unknown | 36 | 97% |
Demographic breakdown
Readers by professional status | Count | As % |
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Student > Bachelor | 9 | 24% |
Student > Ph. D. Student | 6 | 16% |
Researcher | 6 | 16% |
Student > Master | 3 | 8% |
Other | 2 | 5% |
Other | 6 | 16% |
Unknown | 5 | 14% |
Readers by discipline | Count | As % |
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Biochemistry, Genetics and Molecular Biology | 12 | 32% |
Agricultural and Biological Sciences | 8 | 22% |
Immunology and Microbiology | 3 | 8% |
Neuroscience | 2 | 5% |
Materials Science | 2 | 5% |
Other | 5 | 14% |
Unknown | 5 | 14% |