Abstract:
Factors for extending the ability of isolated pluripotent stem cells to generate extraembryonic lineages in vivo, following in vitro culture, herein, chemical extenders of pluripotency (CEP). Methods of extending the ability of a pluripotent cell to generate embryonic and extraembryonic lineages. The cell to be reprogrammed is contacted with effective amounts of the CEPs for a sufficient period of time to reprogram the cell into a chemically induced extended pluripotent cell (ciEPSC). ciEPSC are identified as an extended pluripotent cell based on properties including: (i) morphologically and (ii) functionally for example, based on their ability contribute to both TE and ICM, in vivo. The ciEPSCs can be cultured or induced to differentiate into cells of a desired type, and used in a number of applications, including but not limited to cell therapy and tissue engineering.
Abstract:
Cocktails of chemical inducers of neuron-like properties (CINP) is provided, which includes cAMP agonists, neurogenic small molecules, glycogen synthase kinase inhibitors, TGFβ receptor inhibitors, and BET family bromodomain inhibitors and optionally, a selective inhibitor of ROCK or p38 MAPK. These cocktails are used in a method of inducing neuron-like properties in partially or completely differentiated non-neuronal cells. The method includes contacting cells of a first type (non-neuronal) with the CINPs for a sufficient period of time to result in reprogramming the cell into cells of a second type having neuron-like characteristics (CiNs). Isolated chemically induced neurons (CiNs) can be used in a number of applications, including but not limited to cell therapy.
Abstract:
Provided are chemical inducers of pluripotency (CIP) which include glycogen synthase kinase inhibitors, TGFβreceptor inhibitors, cyclic AMP agonists and S-adenosylhomocysteine hydrolase (SAH) inhibitors or histone acetylators. A method of inducing pluripotency in a partially or completely differentiated cell by using such chemical inducers of pluripotency is also provided. The method includes: (i) contacting a cell with the CIPs for a sufficient period of time to result in reprogramming the cell into a pluripotent stem cell having ESC-like characteristics (CiPSC). Isolated chemically induced pluripotent stem cells (CiPSCs) and their progeny, produced by inducing differentiation of the CiPSCs, can be used in a number of applications, including but not limited to cell therapy and tissue engineering