Methods of differentiating stem cells by modulating MIR-124
Provided herein are methods of differentiating stem cells via modulating miR-124, and the differentiated cells thereby. Also provided herein are methods for the treatment of diseases using the differentiated cells.
1. A method of differentiating an isolated mammalian trophoblast stem cell, the method comprising contacting the isolated mammalian trophoblast stem cell with bFGF (basic fibroblast growth factor), 2-mercaptoethanol and nicotinamide, to induce differentiation of the isolated mammalian trophoblast stem cell to a pancreatic progenitor cell that expresses a marker selected from the group consisting of Ngn3, insulin, and a combination thereof, wherein the isolated mammalian trophoblast stem cell is from a human or a mouse.
2. The method of claim 1 , wherein the isolated mammalian trophoblast stem cell is a human trophoblast stem cell (hTS cell).
3. The method of claim 1 , wherein the method activates miR-124.
4. The method of claim 1 , wherein the concentration of bFGF is no more than 100 ng/mL.
5. The method of claim 1 , wherein the concentration of bFGF is from about 1 to about 100 ng/mL.
6. The method of claim 1 , wherein the concentration of bFGF is about 10 ng/mL.
7. The method of claim 1 , wherein the concentration of 2-mercaptoethanol is from about 0.1 to about 10 mmol/L.
8. The method of claim 7 , wherein the concentration of 2-mercaptoethanol is about 1 mmol/L.
9. The method of claim 1 , wherein the concentration of nicotinamide is from about 1 to about 100 mmol/L.
10. The method of claim 9 , wherein the concentration of nicotinamide is about 10 mmol/L.
11. The method of claim 3 , wherein the miR-124 is miR-124a.
12. The method of claim 3 , wherein the miR-124 is homo sapiens miR-124a (hsa-miR-124a).
13. The method of claim 3 , wherein the miR-124 is hsa-miR-124-5p (SEQ ID NO:1: CGUGUUCACAGCGGACCUUGAU) or a fragment thereof; or hsa-miR-124-3p (SEQ ID NO:2: UAAGGCACGCGGUGAAUGCC) or a fragment thereof.
14. The method of any one of claim 1 , 2 , 3 , 4 - 6 , or 7 - 13 , wherein the pancreatic progenitor cell expresses Ngn3.