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Mieke Geens

Pluripotent stem cells have the potential to differentiate into any cell type of the adult human body. This makes them attractive as in-vitro research model for human development and disease, but also as a cell source for regenerative medicine. We work on the two best known types of human pluripotent stem cells (hPSC): human embryonic stem cells (hESC), derived from surplus human embryos, and human induced pluripotent stem cells (hiPSC), obtained through reprogramming of somatic cells.

A first aim of our group is to elucidate the molecular basis of the differentiation potential of hPSC. Although by definition each hPSC line can differentiate into derivatives of endoderm, mesoderm and ectoderm, significant variation in differentiation potential and efficiency between individual lines exists, often with the occurrence of a marked propensity to differentiate into a specific cell-lineage, e.g. pancreatic, hematopoietic or cardiac cells. Also, some of the cells within the cultures seem to be refractory to differentiation. These residual undifferentiated cells pose a high risk for future clinical applications. Finally, chromosomal abnormalities can alter the differentiation capacity but also the possible malignant characteristics of hPSC. 

A second focus of the group is on X chromosome inactivation (XCI), one of the earliest epigenetic events during human development. In female cells, one of the two X chromosomes is silenced in order to obtain the same gene dosage when compared to male cells that have only one X chromosome. Different appearances of XCI have been described in hPSC, often with repercussions on the applicability of the cells as research model or for clinical use. We are interested in this phenomenon and its effect on derivation efficiency and differentiation potential.

Finally, we are working on the optimization of hPSC derivation, both hESC and hiPSC. We are exploring the hESC derivation potential of single blastomeres of cleavage stage human embryos and work on the improvement of hiPSC derivation protocols from adult somatic cells. The comparison of the epigenetic landscape of these lines with golden standard inner cell mass-derived hESC lines can give us insight in the similarities and differences linked to the donor cells or hPSC derivation technique.

Differentiation bias in hPSC

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X-chromosome inactivation

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Different sources of hPSC

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