Donor dependent variations in hematopoietic differentiation among embryonic and induced pluripotent stem cell lines.. Homo sapiens

Hematopoiesis generated from human embryonic stem cells (ES) and induced pluripotent stem cells (iPS) are unprecedented resources for cell therapy. We compared hematopoietic differentiation potentials from ES and iPS cell lines originated from various donors and derived them using integrative and non-integrative vectors. Significant differences in differentiation toward hematopoietic lineage were observed among ES and iPS. The ability of engraftment of iPS or ES-derived cells in NOG mice varied among the lines with low levels of chimerism. iPS generated from ES cell-derived mesenchymal stem cells (MSC) reproduce a similar hematopoietic outcome compared to their parental ES cell line. We were not able to identify any specific hematopoietic transcription factors that allow to distinguish between good versus poor hematopoiesis in undifferentiated ES or iPS cell lines. However, microarray analysis showed genes differentially expressed in ES and iPS cell lines according to their hematopoietic potential. These results demonstrate the influence of genetic background in variation of hematopoietic potential rather than the reprogramming process. Overall design: Microarray gene expression analysis on EB’s from five pluripotent stem cells (PSC), with good (H1, PB11, PB7) versus poor hematopoietic potential (PB6, PB12). The gene expression profiling was performed on biological replicates of the five cell lines except for the EB derived from PB7 cell line for which one sample was excluded from the transcriptome analysis due to a low RNA yield. The genes were selected on the basis of two criteria p-value ≤ 0.05 and an absolute FC ≥ 2.