Single-cell transcriptional profiling informs efficient reprogramming of human somatic cells into cross-presenting dendritic cells

Submission history

Has received: January 25, 2021

Accepted: January 26, 2022

Thanks

We thank the members of the Pereira laboratory for the discussions. We thank A. Schambach and C. Baum (Institute of Experimental Hematology, Hannover, Germany) for sharing the plasmids pRRL.PPT.SF.GFPpre, pRRL.PPT.PGK.GFPpre and pRRL.PPT.EFS.GFPpre. We thank Z. Kokaia, H. Ahlenius and E. Quist (LSCC, Lund, Sweden) for providing HEFs (ethical permit: Dnr 6.1.8-2887/2017). We also thank healthy donors and the Center for Clinical Immunology and Transfusion Medicine at Skåne University Hospital for the provision of leukocyte concentrates (ethical permit: 2020:14). We thank Lund Center for Translational and Clinical Genomics, SciLifeLab for providing sequencing services. We would also like to thank Lund University Bioimaging Center and Lund Stem Cell Center FACS Facility for scanning electron microscopy and FACS assistance. We thank S. Buschow (Erasmus MC, Rotterdam, The Netherlands) for the discussions.

Funding: Funding for this project was supported by the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation program (Grant Agreement No. 866448), Cancerfonden (CAN 2017/ 745), the Swedish Research Council (2018-02042), NovoNordisk Fonden (0056527) and FCT (CENTRO-01-0145-FEDER-030013) at C.-FP The Knut and Alice Wallenberg Foundation, the Faculty of Medicine of Lund University and Region Skåne are recognized for their financial support. The FFR and the AGF are supported by FCT doctoral grants (SFRH/BD/130845/2017 and SFRH/BD/133233/2017).

Author’s contributions: FFR, CFP, TZ, NA, OZ and AGF conducted reprogramming experiments and analyzed the data. HL and SS achieved BM aspirations and MSC generation. SK contributed with lentiviral vectors. FFR, IK and EH analyzed the scRNA-seq and ChIP-seq datasets. FFR, CFP and C.-FP designed the experiments and wrote the manuscript.

Competing interests: FFR, CFP and C.-FP hold equity interests and hold management positions in Asgard Therapeutics AB, which develops cancer immunotherapies based on DC reprogramming technologies. FFR, CFP and C.-FP are the inventors of patent application PCT/IB2018/052378 owned by Asgard Therapeutics which covers the cell reprogramming approach described here.