Hematopoietic reconstitution with androgenetic and gynogenetic stem cells.
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.
Eckardt
Sigrid
S
Center for Animal Transgenesis and Germ Cell Research, New Bolton Center, University of Pennsylvania, Kennett Square, Pennsylvania 19348, USA.
Leu
N Adrian
NA
Bradley
Heath L
HL
Kato
Hiromi
H
Bunting
Kevin D
KD
McLaughlin
K John
KJ
D000818:Animals; D002454:Cell Differentiation; D002678:Chimera; D053595:Embryonic Stem Cells / Q000637:transplantation*; D015870:Gene Expression; D018392:Genomic Imprinting; D006410:Hematopoiesis / Q000235:genetics; D006412:Hematopoietic Stem Cells / Q000166:cytology*; D007335:Insulin-Like Growth Factor II / Q000235:genetics; D008099:Liver / Q000166:cytology*; D008745:Methylation; D051379:Mice; D010312:Parthenogenesis
C513121:IGF2 protein, mouse; D007335:Insulin-Like Growth Factor II