Notch withdrawal unlocks emergence of CD4 T cells from human iPSCs

T cell progenitors derived from induced pluripotent stem cells fail to effectively differentiate into CD4+ helper cells. Here we describe a key role for the withdrawal of Notch ligand during the final step of stimulation through the T cell receptor to prompt T cell maturation allowing access to the CD4 lineage in iPSC T cells (iT cells).

These CD4+ iT cells produce signature CD4 cytokines and express a transcriptional signature similar to human blood CD4 T cells. We believe this is a key step towards iT cell therapies incorporating both helper and cytotoxic iT cells.