WNT pathway stimulation in reprogramming somatic cells with nuclear reprogramming factors

摘要

The invention provides compositions and methods of use in reprogramming somatic cells. Compositions and methods of the invention are of use, e.g., for generating or modulating (e.g., enhancing) generation of induced pluripotent stem cells by reprogramming somatic cells. The reprogrammed somatic cells are useful for a number of purposes, including treating or preventing a medical condition in an individual. The invention further provides methods for identifying an agent that reprograms somatic cells to a pluripotent state and/or enhances the speed and/or efficiency of reprogramming. Certain of the compositions and methods relate to modulating the Wnt pathway.

主权项

1. A method of reprogramming a mammalian somatic cell, comprising:
(I) introducing into the mammalian somatic cell, one or more retroviral vectors encoding Oct4, and optionally encoding one or more reprogramming factors selected from the group consisting of: Klf4 and Sox2, wherein c-Myc is not introduced into the cell; (II) contacting the mammalian somatic cell with a Wnt-3a conditioned medium; or an agent that modulates the Wnt pathway selected from the group consisting of a recombinant, exogenous, soluble, and biologically active Wnt protein; and a GSK-3 antagonist; and (III) culturing the cells under conditions suitable for reprogramming the mammalian somatic cell to a pluripotent state.