Using a new HSPC aging model in vitro to explore the mechanism of cellular memory in aging HSPCs
Abstract Age-associated changes attenuate human blood system functionality through the aging of hematopoietic stem and progenitor cells (HSPCs). Hematopoietic aging is manifested in human populations in the form of an increase in myeloproliferative disease,therefore, study on hematopoietic stem and progenitor cells (HSPCs) senescence bears great significance to treat hematopoietic associated disease. However, the mechanism of HSPC aging is lacking, especially cellular memory mechanism. Here, we not only reported a new HSPC aging model in vitro, but also propose and verify the cellular memory mechanism of HSPC aging of Polycomb/Trithorax system. In this model cells, the senescence-related β-gal activity, cell cycle, colony-forming ability, aging-related cell morphology and metabolic pathway are significantly changed compare to the young group. Furthermore, we found the model HSPCs have more obvious aging manifestation than those of natural mice and IL3 is the major factor contributing to HSPC aging in the model. We also observed dramatically changes in the expression level of PRC/TrxG complexes. We further identified downstream molecules of PRC/TrxG complexes,Uhrf1 and TopII, which were found to play a critical role in HSPC aging based on the HSPC aging model. So, these findings proposed a new aging HSPC model in vitro which we forecasted could be used to preliminary screen the drugs of the HSPC aging related hemopathy and suggested cellular memory mechanism of HSPC aging.