The top-tier scientific journal Nature published online a paper entitled “Protein competition switches the function of COP9 from self-renewal to differentiation” on Aug 6, 2014. This paper reported a new mechanism how to control the balance between stem cell self-renewal and differentiation. This work was a fruit of the collaboration between the Institute of Biophysics, Chinese Academy of Sciences and the Stowers Institute for Medical Research.

“The balance between stem cell self-renewal and differentiation is controlled by intrinsic factors and niche signals. Some intrinsic factors promote stem cell self-renewal, whereas others stimulate differentiation. However, it remains poorly understood how the balance between self-renewal and differentiation is controlled.” says Professor Dr. Ting Xie from Stowers Institute for Medical Research, correspondence author of the paper.

In this study, researchers took advantage of Drosophilagermline stem cells (GSCs) as biological model and demonstrated that the differentiation factor Bam controls the functional switch of the COP9 complex from self-renewal to differentiation via protein competition. Genetic results in vivo and biochemistry data in vitroindicated that the COP9 complex is intrinsically required for GSCs self-renewal, whereas in differentiating daughter cells, upregulatedBam recruits Csn4 from COP9 complex via protein competition to inactivate the self-renewal function of the COP9 complex and to allow other Csn components to promote GSCs differentiation. In the meantime, the excess Bam also combinesBgcn to form differentiation-driven complex and then to repress self-renewal factors in cytoblasts.

“Because many intrinsic self-renewal factors are ubiquitously expressed in both stem cells and their differentiated progeny, there is an interesting question arising that why stem cells and their daughter cells share common intrinsic factors but have a different fate. Protein competition could be employed as a common mechanism for balancing stem cell self-renewal and differentiation in various stem cell systems.” says Dr. Lei Pan from the Institute of Biophysics, first author of the paper.

This work was supported by grants from the Ministry of Science and Technology of China, the National Science Foundation of China, and the US National Institutes of Health and the Stowers Institute for Medical Research.

Fig. A working model illustrating how Bam converts the function of the COP9 complex from self-renewal to differentiation by sequestering Csn4 via protein competition.