In 2006, Japanese scientist Shinya Yamanaka reprogrammed mouse somatic cells by transferring four "stem genes" to induce pluripotent stem cells (iPS cells). The field has had an important impact. The current view is that stem cells and differentiation genes in stem cells "do their job" and inhibit each other. Stem genes are only highly expressed in stem cells, inhibiting differentiation genes, and maintaining cell stemness; while differentiation genes are only highly expressed in differentiated cells, suppressing stem genes and changing the pluripotent state of stem cells leading to their differentiation.
However, through collaborative research, Professor Deng Hongkui and Professor Tang Chao of Peking University found that in the process of somatic cells being induced into pluripotent stem cells, vital stem genes can be replaced by genes that control differentiation. They used the data obtained to propose a "seesaw model" of stem cell fate determination. This model can better understand the relationship between the suppression and balance of stem genes and differentiation genes in the germ layer, and this relationship may determine stem cells. fate. According to the prediction of this model, if the differentiation genes of mesoderm and ectoderm are overexpressed at the same time, by changing the balance, it shows the effect of replacing multiple stem genes. Further experimental results also confirmed this prediction. For the first time, they achieved the simultaneous replacement of the two stem genes that were at the core of somatic cell induction into pluripotent stem cells with mesoderm and ectoderm differentiation genes.
This achievement changed the traditional view that somatic cells induced into pluripotent stem cells required high expression of stem genes, re-recognized the mechanism of cell fate determination, and provided a new perspective for studying the change of cell fate. This achievement was recently reported by Cell Magazine in the form of a cover paper with the title "Induction of Pluripotency in Mouse Somatic Cells with Lineage Specifiers".
The research was supported by the National Natural Science Foundation of China's major research project "Epigenetic Mechanisms of Cell Programming and Reprogramming."
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