In vivo and in vitro differentiation of uniparental embryonic stem cells into hematopoietic and neural cell types.

The biological role of genomic imprinting in adult tissue is central to the consideration of transplanting uniparental embryonic stem (ES) cell-derived tissues. We have recently shown that both maternal (parthenogenetic/gynogenetic) and paternal (androgenetic) uniparental ES cells can differentiate, both in vivo in chimeras and in vitro, into adult-repopulating hematopoietic stem and progenitor cells. This suggests that, at least in some tissues, the presence of two maternal or two paternal genomes does not interfere with stem cell function and tissue homeostasis in the adult. Here, we consider implications of the contribution of uniparental cells to hematopoiesis and to development of other organ systems, notably neural tissue for which consequences of genomic imprinting are associated with a known bias in development and behavioral disorders. Our findings so far indicate that there is little or no limit to the differentiation potential of uniparental ES cells outside the normal developmental paradigm. As a potentially donor MHC-matching source of tissue, uniparental transplants may provide not only a clinical resource but also a unique tool to investigate aspects of genomic imprinting in adults.