Translational control in pluripotent cells by SBDS-dependent ribosome destabilization

Unique traits of pluripotent stem cells are not fully known. Using thermal proteome profiling, we identified reduced stability of ribosomes in induced pluripotent cells (iPSCs) compared to that in somatic cells. Also, iPSCs exhibited lower protein synthesis rate and lower expression of a ribosome maturation factor, the Shwachman-Bodian-Diamond Syndrome protein (SBDS). Differentiation of iPSCs led to upregulation of SBDS and knock-down of SBDS slowed the differentiation while increasing expression of master pluripotency markers NANOG and Oct-4. Mutations in the SBDS gene have been shown to impair ribosome assembly and to inhibit differentiation of hematopoietic stem cells causing the Shwachman- Diamond syndrome. Physiological SBDS-dependent destabilization of ribosomes appears to be a tool for translational control providing robustness to the state of pluripotency.