Chemical Reprogramming of Human T Cells to Pluripotent Stem Cells

Chemical reprogramming provides an innovative approach to convert somatic cells into pluripotent state using small molecules, holding great promise for regenerative medicine. Since the successful generation of human chemically induced pluripotent stem (hCiPS) cells in 2022, this strategy has emerged as a powerful tool for inducing pluripotency in diverse cell types. However, whether terminally differentiated somatic cells with stable identities, such as T cells, could be chemically reprogrammed toward pluripotency, remains unknown. Here, we adapted a chemical reprogramming method to successfully reprogram CD3+ and CD8+ T lymphocytes into hCiPS (hT-CiPS) cells. These cells fulfilled characteristics of human pluripotent stem cells, and TCR rearrangements analysis confirmed their T cell origin. Moreover, hT-CiPS cells can efficiently generate TCR-expressing cells and re-differentiate to CD4/CD8 positive T cells. Our findings reveal that chemical reprogramming can effectively convert terminally differentiated cells into pluripotent cells, holding promise for clinical applications in immunotherapy and regenerative medicine. Overall design: A total of 22 bulk RNA-seq data were analyzed, including those from CD3T, CD8T, hCiPSC, and S1 cells. Each condition has 2 biological replicates.