Presenting Author:
Sanders Oh, B.S.
Principal Investigator:
John Kessler, M.D.
Department:
Neurology, Ken and Ruth Davee Department
Keywords:
pluripotent, totipotent, embryonic stem cell, reprogramming, differentiation, cell lineage, early development, stem cell... [Read full text]
Location:
Third Floor, Feinberg Pavilion, Northwestern Memorial Hospital
B103 - Basic Science
Reprogramming Mouse Pluripotent Stem Cells toward Totipotency
Earliest developmental cell has the greatest lineage potential and has the ability to revolutionize regenerative medicine by generating all of patient-specific cell types. Cell changes have been once believed to only occur down the lineage potential gradient from higher energy and undifferentiated toward lower energy and differentiated. The reversal of cell lineage development and expansion of potential has been shown possible by successfully reprogramming terminally differentiated somatic cells to induced-pluripotent stem cells. Despite the success, induced-pluripotent stem cells have shown to retain previous epigenetic memories and can be challenging to faithfully differentiate toward certain cell types. Currently there has been no approved clinical therapy which suggests that a better source is needed. The cell with the highest potential and plasticity, which pluripotent cell descends from, is totipotent cell. The process of reprogramming towards totipotency is unknown, and no one has yet to show that this is possible with defined factors. Here we have identified some key maternal factors that are involved in chromatin remodeling which appear to play a role in inducing totipotency. These factors can reactivate endogenous retroviral elements that are active during totipotent development but inactive during pluripotency. The reprogrammed cells upregulate genes that are associated with totipotency while downregulating key pluripotent genes. When these maternal factors are combined with p150 siRNA and low-dose trichostatin A, the overall transcriptome of reprogrammed cells share even more similarities toward totipotent state. Furthermore, these reprogrammed cells are able to survive in totipotent culture medium which is normally cytotoxic to pluripotent cells. The reprogrammed cells express these totipotent-like properties while maintaining normal karyotype. Interestingly, telomere lengthening was observed in reprogrammed cells which may indicate the reversal of aging. These findings suggest that reprogramming a cell towards totipotency using defined factors may be possible and provide potential new source of therapy for regenerative medicine.
