The present invention generally relates to methods and compositions to generate a secondary iPS (2iPS)
cell to produce somatic cells of a rare differentiation
cell type fate. In some embodiments, the method relates to an increase in efficiency of differentiation and production of high yields of somatic cells of a rare differentiation
cell type fate produced from secondary iPS (2iPS) cells as compared to their differentiation from other pluripotent
stem cell sources such as ES cells or primary iPS cells. In some embodiments, the present invention relates to compositions, methods and systems for
reprogramming a first
somatic cell into a primary iPS cell, where the primary iPS cell is then differentiated along a selected linage to produce a second
somatic cell, which is then reprogrammed to a secondary iPS cell (2iPS) cell. The 2iPS cell has a high efficiency of differentiating into a cell of the same
cell type as the second
somatic cell, e.g., a somatic cells of a rare differentiation
cell type fate such as but not limited to a ventricular cardiomyocyte, a pancreatic β-cell or a hepatic cell. In some embodiments, the first somatic cell is a
fibroblast, or a
cardiac cell, but is not limited to
cardiac fibroblast cells. In some embodiments, the present invention relates to compositions, methods and systems to produce ventricular cardiomyocytes from secondary induced pluripotent stem cells (iPSC), where the iPSC are themselves generated from ventricular cardiomyocytes. The secondary iPS (2iPS) cell generated from ventricular cardiomyocytes have a higher cardiomyogenic potential and high cardiomyogenic yield as compared to primary iPSC, and are useful in
drug discovery,
disease modeling and cell-based therapy.