Gene expression in blastomeres after transfer of somatic cells into human oocytes

The exchange of the oocyte's genome with the genome of a somatic cell, followed by the derivation of pluripotent stem cells, could enable the generation of specific cell types affected in degenerative human diseases. Such cells, carrying the patient's genome, might be useful for cell replacement. Here we report that the development of human oocytes activated after genome exchange invariably arrests at the late cleavage stages in association with transcriptional abnormalities. In contrast, if the oocyte genome is not removed and the somatic cell genome is merely added, they efficiently develop to the blastocyst stage. Human stem cell lines derived from these blastocysts differentiate into cell types of all three germ layers, and a pluripotent gene expression program is established on the genome derived from the somatic cell. This result demonstrates the feasibility of reprogramming human cells using oocytes and identifies the removal of the oocyte genome as the primary cause of developmental failure after genome exchange. Future work should focus on the critical elements that are associated with the human oocyte genome.

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Noggle S, Fung HL, Gore A, Martinez H, Satriani KC, Prosser R, Oum K, Paull D, Druckenmiller S, Freeby M, Greenberg E, Zhang K, Goland R, Sauer MV, Leibel RL, Egli D