Donor Dependent Variations in Hematopoietic Differentiation among Embryonic and Induced Pluripotent Stem Cell Lines

Abstract

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. There is a relatively unpredictable variation in hematopoietic differentiation between ES and iPS cell lines that could not be predicted based on phenotype or gene expression of the undifferentiated cells. These results demonstrate the influence of genetic background in variation of hematopoietic potential rather than the reprogramming process.

High-Diversity Mouse Populations for Complex Traits

“…Patient-derived pluripotent stem cell lines exhibit phenotypic variability, which affects differentiation and impedes universal protocol development to produce clinically relevant cell types. Patient-donor genetic variation is a primary driver of interline variability [91][92][93] and caQTL and eQTL have been mapped in large, genetically diverse panels of these differentiated human iPSCs [94]. However, low genetic resolution in these small-sample-size human studies limits the functional validation of variants underlying QTL [93,95].…”

Kidney organoid reproducibility across multiple human iPSC lines and diminished off target cells after transplantation revealed by single cell transcriptomics

“…To explore whether the iPSC-line associated differences were associated with their basal state (Burrows et al, 2016;Féraud et al, 2016) at D0 or the process of differentiation, we compared the single cell profiles collected at D0,7, and 15 for each organoid culture.…”

Genetic variation influences pluripotent ground state stability in mouse embryonic stem cells through a hierarchy of molecular phenotypes

“…Genetic background also strongly influences molecular phenotypes and differentiation capacity in human ESCs and induced pluripotent stem cells (hiPSCs). Differences between genetic backgrounds are a dominant source of inter-line variability in hESCs and hiPSCs (Burrows et al, 2016;Carcamo-Orive et al, 2017;Choi et al, 2015;DeBoever et al, 2017;Féraud et al, 2016;Kajiwara et al, 2012;Kyttälä et al, 2016;Osafune et al, 2008;Ramos-Mejia et al, 2010). QTL mapping in panels of differentiated hiPSCs has revealed loci controlling transcript abundance and chromatin accessibility in lineage-committed cells Schwartzentruber et al, 2018).…”