The Mechanism Of RUNX1a Enhances Hematopoietic Lineage Commitment From Human Embryonic Stem Cells

Transplantation of hematopoietic stem cells can be used to treat leukemia and other blood diseases, But it’s hard to acquire enough number of HSC cells. RUNXla is an important transcription factor regulates human pluripotent stem cells generating hematopoietic progenitor cells (HPCs). Ectopic expression of RUNXla facilitates emergence of HPCs.but the molecular mechanism behind RUNXla-mediated HSC development remain poorly understood. In this project,we use ectopic expression RUNX1a mediated HSC model. Then we performed global gene expression profiling during three time points:two days after ectopic expression of RUNXla in human embryonic stem cell (days0), emerging hematopoietic progenitor cells (days6),50%hematopoietic stem progenitor cells appeared (days11). Analysis of global features of the RUNXla regulatory network by ChlP-seq and RNA-seq.dayO,RUNXla involved in RNA processing and metabolism.After day6, RUNX1a target genes play a role in vascular endothelial cell development. Day11,RUNX la involved in hematopoiesis-related functions. When ectopic expression of RUNX1a,the important transcription factor HOXB4and FLll expression increased during the differentiation process.It’s indicated RUNXla may be an upstream regulator during early hematopoietic differentiation.In addition,WNT and BMP signaling pathway dynamically changed, suggesting that these two signal paths may be partially involved in the RUNXla transcriptional regulation network. In summary, our study confirmed ectopic expression RUNX1a can accelerate hematopoietic stem cell formation,and RUNX1regulatory network is highly dynamic.Analysis of ectopic expression of RUNX1a transcriptional programme, providing clues for RUNXla enhancing hematopoietic lineage commitment of hPSCs.