Method of generating multipotent stem cells

A method of generating multipotent stem cells, comprising the step of delivering the at least one reprogramming protein into the somatic cells,

• wherein the at least one reprogramming protein comprises at least one Master Regulator (MR) protein,
• wherein the somatic cells comprise endogenous somatic cells,
• wherein the at least one Master Regulator (MR) protein is selected from the group consisting of BAZ2B, ZBTB20, ZMAT1, CNOT8, KLF12, DMTF1, HBP1, FLI1, and combinations thereof, and
• wherein the at least one Master Regulator (MR) protein comprises BAZ2B.

A method of identifying Master Regulator (MR) proteins involved in onset driving events of lineage-committed cells, comprising the steps of:

• a) obtaining bi-species heterokaryons by fusing embryonic stem cells (ESCs) of a first species with lineage-committed cells of a second species;
• b) tracking reprogramming of nuclei of the lineage-committed cells to a multipotent state by transcript profiling of mRNA of the second species at multiple timepoints after fusion;
• c) interrogating a regulatory network of the lineage-committed cells with gene expression signatures collected in step b) to identify candidate MR proteins;
• and
• d) validating the candidate MR proteins identified in step c) by ectopically expressing the candidate MR proteins in lineage-committed cells and progenitors thereof, and evaluating effectiveness of the candidate MR proteins in reprogramming committed lineage-committed cells and progenitors thereof into a multipotent state, thereby identifying MR proteins involved in onset driving events of the lineage-committed cells.