GSE69932
Comparison of the transcriptome and chromatin state between human cord blood HSC and human iPSC derived hematopoietic progenitor using next-generation sequencing
We analyzed the transcriptome and transposase accessible chromatin–using RNAseq and ATAC-seq, respectively–of human cord blood hematopoietic stem cells and human iPSC derived hematopoietic progenitors. iPSC-derived HPCs were FACS sorted CD34+/CD43+ cells. We also examined the effect of inhibiting Wnt signaling during the second week of hematopoietic differentiation of hiPSC. The integrated transcriptomic, epigenomic and functional analyses not only uncovered novel molecular differences between hPSC- HPCs and native HSCs, but also enabled us to target these differences with small molecules to improve derivation and function of hPSC derived HPCs. The strategies here delineated could also be useful for increasing the production of blood cell types such as erythrocytes for therapeutic purposes. Given the existence of a multitude of small molecules specifically targeting a wide range of molecular pathways, our approach could provide a comprehensive strategy for reconstituting the authentic HSC regulatory program and thus open up new avenues for de novo generation of HSCs from hPSCs. Overall design: Examination of the whole transcriptome and transposase accessible chromatin in 2 cell types.