Hematopoietic reconstitution with androgenetic and gynogenetic stem cells

Abstract

Parthenogenetic embryonic stem (ES) cells with two oocyte-derived genomes (uniparental) have been proposed as a source of autologous tissue for transplantation. The therapeutic applicability of any uniparental cell type is uncertain due to the consequences of genomic imprinting that in mammalian uniparental tissues causes unbalanced expression of imprinted genes. We transplanted uniparental fetal liver cells into lethally irradiated adult mice to test their capacity to replace adult hematopoietic tissue. Both maternal (gynogenetic) and paternal (androgenetic) derived cells conveyed long-term, multilineage reconstitution of hematopoiesis in recipients, with no associated pathologies. We also establish that uniparental ES cells can differentiate into transplantable hematopoietic progenitors in vitro that contribute to long-term hematopoiesis in recipients. Hematopoietic tissue in recipients maintained fidelity of parent-of-origin methylation marks at the Igf2/H19 locus; however, variability occurred in the maintenance of parental-specific methylation marks at other loci. In summary, despite genomic imprinting and its consequences on development that are particularly evident in the androgenetic phenotype, uniparental cells of both parental origins can form adult-transplantable stem cells and can repopulate an adult organ.