EZH2 inhibitor GSK126 promotes human iPSC hematopoietic differentiation

However, existing protocols often result in the production of immature progenitors with limited multilineage engraftment capacity in vivo. This limitation is believed to be due to an epigenetic barrier, particularly involving the Polycomb Repressor Complex 2 (PRC2), which mediates transcriptional repression during hematopoietic development through H3K27me3 methylation.

In this study, we explored the suppression of EZH2, a key component of PRC2, using the small molecule inhibitor GSK126 at various stages of iPSC differentiation. Our findings revealed that EZH2 inhibition leads to an increase in phenotypic HSCs and enhances long-term colony-forming unit (CFU) colony formation. Single-cell RNA sequencing further demonstrated that GSK126 promotes iPSC hematopoietic differentiation.