REPROcode Developed to Accelerate Reprogramming of Immune Cells

Scientists at Lund University have developed REPROcode, a combinatorial single‑cell screening platform that identifies transcription factor (TF) combinations capable of reprogramming accessible cells into specific immune cell types. 

Direct reprogramming offers opportunities to generate rare immune populations important for fighting disease, yet progress has been hindered by limited understanding of the transcriptional networks that define immune cell states. Using REPROcode, the Lund team created a library of over 400 immune-related factors, each labelled with a unique DNA barcode. Using this system, they were then able to test thousands of combinations simultaneously and track which ones triggered the conversion to specific immune cells.

To validate the platform, the team induced type‑1 conventional dendritic cells (cDC1s) using multiplexed TF sets of 9, 22, and 42 factors. REPROcode’s high‑throughput design revealed optimal transcription factor stoichiometry, fidelity enhancers, and regulators that control cDC1 developmental states. The researchers then broadened their analysis by constructing a lentiviral array of 408 TFs to map broader immune cell potential. Screening 48 TFs enriched in dendritic cell subsets produced both myeloid and lymphoid phenotypes and enabled a TF hierarchy map that serves as a guide for cell fate engineering. 

“It took us four years to develop the screening technique and complete the library,” said Filipe Pereira, lead author of the study published in Cell Systems. “This is the foundation for subsequently creating ‘recipes’ for reprogramming immune cells.” Beyond dendritic cells, REPROcode was also used to generate natural killer (NK)‑like cells.

The discovery underscores how transcription factor interactions regulate immune identity and highlights a route toward tailoring immune cell production for therapy. Pereira emphasized that the approach could eventually support precision reprogramming for cancer, autoimmune disorders, and tissue repair applications.