In the past year supported by CIRM funding we have made substantial progress in a number of areas related to stem cells and regenerative medicine. We published 6 papers including 5 supported by CIRM during this time.
We published only the second study ever on the metabolomics of induced pluripotent stem cells (iPSC), finding they are almost, but not entirely reprogrammed at the metabolic level to resemble embryonic stem cells (ESCs). Some notable differences between iPSC and ESCs include how they metabolized sugars. This study could have important implications for development of new iPSC production methods and improved iPSC safety and clinical efficacy.
We also published a study comparing the transcriptomes of iPSC and cancer cells. The transcriptomes are the total pattern of transcribed RNAs in cells, which can tell important stories about how the cells are programmed and functioning. Importantly, iPSC and cancer cells shared striking similarities in a number of ways in our findings including inhibition of differentiation and induction of specific metabolic programs. It was notable, however, that iPSC and cancer cells also differed in some important ways including high expression of pluripotency-related factors in iPSC was absent in the cancer cells. We also found that we could convert the cancer cells to behave more like iPSC through a form of cancer reprogramming that could have substantial import for developing new cancer treatments.
In another published study we reported the transcriptome that is regulated by Myc and its cofactor GCN5 in neural stem cells. Interestingly, Myc and GCN5-regulated genes were significantly overlapping, supporting the notion that these two factors often work together to regulate neural stem cell fate. However, the two factors also diverged in some ways suggesting that they work independently as well. Importantly, knockout of Myc or of GCN5 independently specifically in neural stem cells generated very similar phenotypes in mice. In each case the mice had very small brains, supporting a model in which Myc and GCN5 cooperate in neural stem cells to drive brain growth.