Methods of controlling cell fate and consequences for disease
Provided herein are methods for performing cellular reprogramming that include treatment of somatic cells with an inhibitor of CAF-1, Sumo2, Nutd21, or combinations thereof prior to or during a reprogramming procedure. Such inhibitors can improve both the speed and efficiency of cellular reprogramming. Inhibitors of the CAF-1 complex can also be used in the treatment of cancer.
1. A method for performing cellular reprogramming, the method comprising:
(a) contacting a somatic cell with an inhibitor of the CAF-1 complex, and an inhibitor of Nudt21, and
(b) subjecting the somatic cell to a reprogramming protocol,
thereby reprogramming the somatic cell to an induced pluripotent stem cell (iPSC).
2. The method of claim 1 , wherein the speed and/or efficiency of cellular reprogramming to iPSCs is increased in the presence of the inhibitors as compared to the speed and/or efficiency of cellular reprogramming performed in the absence of the inhibitors.
3. The method of claim 2 , wherein the measure of efficiency of cellular reprogramming comprises an increase in the total number of reprogrammed cells relative to reprogramming in the absence of said inhibitors, and/or wherein the measure of speed of cellular reprogramming comprises the appearance of reprogrammed cells at an earlier time point than occurs when reprogramming in the absence of said inhibitors.
4. The method of claim 1 , wherein at least one of the inhibitors comprises an RNA interference molecule or an antibody.
5. The method of claim 1 , wherein step (a) is performed before or during step (b).
6. The method of claim 1 , wherein the reprogramming of step (b) comprises induction of Oct-4/Klf4/Sox-2/c-Myc (OKSM) expression.
7. The method of claim 1 , wherein the reprogramming step does not comprise forced expression of c-Myc.
8. The method of claim 1 , wherein the somatic cell comprises a fibroblast.
9. The method of claim 1 , wherein the inhibitor of the CAF-1 complex inhibits the Chaf1a and/or Chaf1b subunit of the CAF-1 complex.
10. A method for performing cellular reprogramming, the method comprising:
(a) contacting a somatic cell with an inhibitor of Nudt21, and
(b) subjecting the somatic cell to a reprogramming protocol,
thereby reprogramming the somatic cell to an induced pluripotent stem cell (iPSC).