Cell Rep. 22, 860–868 (2018)

Unequal cell division leads to distinct daughter-cell fates. In Cell Reports, Reiner and colleagues report that activated lymphocytes show polarization of phosphatidylinositol-(3,4,5)-triphosphate and phosphatidylinositol-3-OH kinase (PI(3)K), initiated during the formation of immune synapses, that is aligned with microtubule-organizing centers and is maintained throughout cell division. This asymmetry of PI(3)K activity also causes unequal division of nutrient receptors, such as the glucose transporter Glut1, between sibling daughter cells during cytokinesis and thereby establishes differences in their metabolic capacity. T cells with higher expression of Glut1 suppress expression of the transcription factor TCF-1; similarly, B cells with high expression of Glut1 downregulate expression of the transcription factor Pax5. These findings suggest that cellular asymmetry in PI(3)K can lead to differences in cell-fate potential.