Indefinite Self-Renewal of ESCs through Myc/Max Transcriptional Complex-Independent Mechanisms

SummaryEmbryonic stem cells (ESCs) can self-renew indefinitely under the governance of ESC-specific transcriptional circuitries in which each transcriptional factor regulates distinct or overlapping sets of genes with other factors. c-Myc is a key player that is crucially involved in maintaining the undifferentiated state and the self-renewal of ESCs. However, the mechanism by which c-Myc helps preserve the ESC status is still poorly understood. Here we addressed this question by performing loss-of-function studies with the Max gene, which encodes the best-characterized partner protein for all Myc family proteins. Although Myc/Max complexes are widely regarded as crucial regulators of the ESC status, our data revealed that ESCs do not absolutely require these complexes in certain contexts and that this requirement is restricted to empirical ESC culture conditions without a MAPK inhibitor.

Graphical AbstractFigure optionsDownload full-size imageDownload high-quality image (100 K)Download as PowerPoint slideHighlights► Ablation of Max in ESCs induces a loss of pluripotency and cell death in this order ► MAP kinase signaling is involved in the detrimental phenotype of Max-null ESCs ► Forced Nanog expression confers unlimited self-renewal on Max-null ESCs ► The two-inhibitor condition renders Max redundant for ESC indefinite self-renewal