We used transcription-profiling to identify mitogen-activated protein kinase (Mapk) signaling as an important regulator involved in the differentiation of oligodendrocyte progenitor cells (OPCs) into oligodendrocytes. We show in tissue culture that activation of Mapk signaling by elevation of intracellular levels of cAMP using administration of either dibutyryl-cAMP or inhibitors of the cAMP-hydrolyzing enzyme phosphodiesterase-4 (Pde4) enhances OPC differentiation. Finally, we demonstrate that systemic delivery of a Pde4 inhibitor leads to enhanced differentiation of OPCs within focal areas of toxin-induced demyelination and a consequent acceleration of remyelination.
Retinoid X receptor gamma signaling accelerates CNS remyelination.
Specimen part
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Human oocytes reprogram somatic cells to a pluripotent state.
Specimen part
View SamplesThe 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.
Human oocytes reprogram somatic cells to a pluripotent state.
Specimen part
View SamplesThe exchange of the oocytes 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 patients 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.
Human oocytes reprogram somatic cells to a pluripotent state.
Specimen part
View Samples