Reprogramming of cells to a new fate
AssigneeThe Scripps Research Institute
InventorsJem A. Efe, Janghwan Kim, Saiyong Zhu, Simon Hilcove, Sheng Ding
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Abstract
The present invention generally provides methods and compositions for transdifferentiation of an animal cell from a first non-pluripotent cell fate to a second non-pluripotent cell fate. Also provided are methods and compositions for the transdifferentiation of an animal cell from a non-pluripotent mesodermal, endodermal, or ectodermal cell fate to a different non-pluripotent mesodermal, endodermal, or ectodermal cell fate.
Claims13
A pharmaceutical composition comprising an isolated population of cells having a second non-pluripotent cell fate, wherein the cells are obtained by a method of converting animal cells from a first non-pluripotent cell fate, and wherein the method comprises:
- (a) introducing a polynucleotide encoding an Oct4 polypeptide, and optionally one or more reprogramming factors comprising polynucleotides encoding a Klf polypeptide, a Sox2 polypeptide, or a c-Myc polypeptide, into cells having a first non-pluripotent cell fate, or contacting cells having a first non-pluripotent cell fate with an Oct4 polypeptide, and optionally one or more reprogramming factors comprising a Klf polypeptide, a Sox2 polypeptide, or a c-Myc polypeptide;
- (b) limiting the expression of endogenous Nanog in the cells from step (a) to a level substantially lower than the level of expression of endogenous Nanog in an induced pluripotent cell (iPSC), thereby generating a non-pluripotent intermediate cell;
- and
- (c) inducing differentiation of the cells from step (b) under conditions to generate the population of cells having the second non-pluripotent cell fate, wherein the cells having the first non-pluripotent cell fate are mesodermal, ectodermal or endodermal cells, and wherein the cells having the second non-pluripotent cell fate from step (c) are in the same or different cell lineage as the cells having the first non-pluripotent cell fate.
A method of manufacturing a population of cells having a second non-pluripotent cell fate obtained by a method of converting animal cells having a first non-pluripotent cell fate, wherein the method comprises:
- (a) (i) introducing factors comprising polynucleotides encoding an Oct4 polypeptide and encoding one or more of a Klf polypeptide, a Sox2 polypeptide, or a c-Myc polypeptide, into cells having a first non-pluripotent cell fate, or (ii) contacting cells having a first non-pluripotent cell fate with an Oct4 polypeptide and one or more reprogramming factors comprising a Klf polypeptide, a Sox2 polypeptide, or a c-Myc polypeptide;
- (b) limiting the expression of endogenous Nanog in the cells from step (a) to a level substantially lower than the level of expression of endogenous Nanog in an induced pluripotent cell (iPSC);
- and
- (c) inducing differentiation of the cells from step (b) under conditions to generate the population of cells having the second non-pluripotent cell fate, wherein the cells having the first non-pluripotent cell fate are mesodermal, ectodermal or endodermal cells, and wherein the cells having the second non-pluripotent cell fate from step (c) are in the same or different cell lineage as the cells having the first non-pluripotent cell fate.
Dependencies are inferred from the claim text.