Metabolic Maintenance of Cell Asymmetry following Division in Activated T Lymphocytes

Asymmetric cell division (ACD)—the partitioning of cellular components in response to polarizing cues during mitosis—plays roles in differentiation and development(1). ACD is important for the self-renewal of neuroblasts in C. elegans and fertilized zygotes in Drosophila, and participates in the development of mammalian nervous and digestive systems(1). T lymphocytes, upon activation by antigen-presenting cells (APC), can undergo ACD, wherein the daughter cell proximal to the APC is more likely to differentiate into an effector-like T cell and the distal daughter more likely to differentiate into a memory-like T cell(2). Upon activation and prior to cell division, expression of the transcription factor c-Myc drives metabolic reprogramming, necessary for the subsequent proliferative burst(3). We found that during the first division of an activated T cell, c-Myc can sort asymmetrically. Asymmetric amino acid transporter distribution, amino acid content, and TORC1 function correlate with c-Myc expression, and both amino acids and TORC1 activity sustain the differences in c-Myc expression in one daughter over the other. Asymmetric c-Myc levels in daughter T cells affect proliferation, metabolism, and differentiation, and these effects are altered by experimental manipulation of TORC1 activity or Myc expression. Therefore, metabolic signaling pathways cooperate with transcription programs to maintain differential cell fates following asymmetric T cell division.