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The Role of ERK Signaling in Hematopoietic Differentiation from hESCs
Wang Hongtao#, Liu Xin#, Wang Mengge, Su Pei, Zhang Leisheng, Liu Cuicui, Wang Yu, Wu Dan, Tu Qian, Zhou Jiaxi*
Stata Key Laboratory of Experimental Hematology, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin 300020, China
Abstract: Extracellular regulated protein kinase (ERK) pathway has been reported to play a critical role in hematopoiesis in zebrafish and mouse. However， the role of ERK pathway in hematopoietic differentiation from human embryonic stem cells (hESCs) remains unclear. In this study， we investigated the role of ERK pathway in hematopoietic specification from hESCs by taking the advantage of a chemical defined hematopoietic differentiation model and PD98059， a specific inhibitor of ERK pathway. The results of immunofluorescence and flow cytometry analysis revealed that PD98059 treatment significantly inhibited the generation of CD43 positive hematopoietic stem and progenitor cells (HSPCs). Further studies demonstrate that PD98059 suppresses hematopoietic differentiation through inhibiting the generation of APLNR positive lateral plate mesoderm cells. The addition of PD98059 in the stage of lateral plate mesoderm cell generation and the whole process of hematopoietic differentiation shows similar inhibitory effect on the generation of HSPCs. Taken together， our findings indicate that the inhibition of ERK pathway suppresses hematopoietic differentiation from hESCs through repressing the generation of lateral plate mesoderm cells. This study provides a theoretical foundation for the establishment of a highly efficient hematopoietic differentiation system of hESCs and the large-scale production of functional blood cells in vitro.
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