REPROcode
Kurochkin I, Altman AR, Caiado I, Pértiga-Cabral D, Halitzki E, Minaeva M, Zimmermannová O, Henriques-Oliveira L, Klein D, Nair M, Oliveira D, Cajal LR, Knittel R, Feick C, Ringnér M, Martin M, Cirovic B, Pires CF, Rosa FF, Sitnicka E, Theis FJ, Pereira CF
2026 · Cell systems
Direct reprogramming of immune cells holds promise for immunotherapy but is constrained by limited knowledge of transcription factor (TF) networks.
Abstract
From the original paper, Cell systems · PubMed
Direct reprogramming of immune cells holds promise for immunotherapy but is constrained by limited knowledge of transcription factor (TF) networks. Here, we developed REPROcode, a combinatorial single-cell screening platform to identify TF combinations for immune cell reprogramming. We first validated REPROcode by inducing type-1 conventional dendritic cells (cDC1s) with multiplexed sets of 9, 22, and 42 factors. With cDC1-enriched TFs, REPROcode enabled identification of optimal TF stoichiometry, fidelity enhancers, and regulators of cDC1 states. We then constructed an arrayed lentiviral library of 408 barcoded immune TFs to explore broader reprogramming capacity. Screening 48 TFs enriched in dendritic cell subsets yielded myeloid and lymphoid phenotypes and enabled the construction of a TF hierarchy map to guide immune reprogramming. Finally, we validated REPROcode's discovery power by inducing natural killer (NK)-like cells. This study deepens our understanding of immune transcriptional control and provides a versatile toolbox for engineering immune cells to advance immunotherapy.
Summary
Editorial summary pending review by the maintainer. The paper's own abstract appears above; the Atlas summary in the maintainer's voice will explain how REPROcode relates to the cross-modality inverse-design framework of the review.
Why this level
Level 0 because the method scores features against a target/background contrast without modelling an intervention — the output is a ranked list of candidate identity determinants, not an intervention whose effect has been computed. Representation family is signature / state-matching. Cited in §3.1 of the review. Editorial rationale pending review by the maintainer.