MEIS2 regulates endothelial to hematopoietic transition of human embryonic stem cells by targeting TAL1
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(2018) 9:340
RESEARCH
Open Access
MEIS2 regulates endothelial to hematopoietic transition of human embryonic stem cells by targeting TAL1 Mengge Wang1,2†, Hongtao Wang1,2†, Yuqi Wen1,2, Xiaoyuan Chen1,2, Xin Liu1,2, Jie Gao1,2, Pei Su1,2, Yuanfu Xu1,2, Wen Zhou3, Lihong Shi1,2* and Jiaxi Zhou1,2*
Abstract Background: Despite 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. Methods: In 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. Results: In 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. Conclusions: Our findings advance the understanding of human hematopoietic development and may provide new insights for large-scale generation of functional blood cells for clinical applications. Keywords: MEIS2, Hematopoiesis, EHT
Background Hematopoietic stem cell transplantation remains to be the only effective approach to treat patients with hematopoietic disorders, such as leukemia, lymphoma, and sickle cell anemia [1]. However, the scarcity of HLA-matched HSCs severely limits the clinical applications [2]. Thus, there is a strong need to find alternative sources to generate HSCs in vitro to meet the clinical demand. Human pluripotent stem cells (hPSCs), including human embryonic stem cells (hESCs) and human induced pluripotent stem cells (hiPSCs), represent * Correspondence: [email protected]; [email protected] † Mengge Wang and Hongtao Wang contributed equally to this work. 1 State Key Laboratory of Experimental Hematology, Institute of Hematology and Blood Diseases Hospital, Tianjin 300020, China Full list of author information is available at the end of the article
a promising source for the generation of HSCs due to its self-renewal ability and multi-lineage differentiation potential [3]. Since the hematopoietic differentiation capacity of hESCs was first confirmed in 2009 by Dr. James A. Thomson’s group [4], significant advantages have been made in the field of hematopoietic differentiation from hPSCs, including t
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