PMID- 34123352 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20220204 IS - 2042-8898 (Print) IS - 2042-8901 (Electronic) IS - 2042-8898 (Linking) VI - 11 IP - 4 DP - 2021 Jun TI - Logical modelling of in vitro differentiation of human monocytes into dendritic cells unravels novel transcriptional regulatory interactions. PG - 20200061 LID - 10.1098/rsfs.2020.0061 [doi] LID - 20200061 AB - Dendritic cells (DCs) are the major specialized antigen-presenting cells, thereby connecting innate and adaptive immunity. Because of their role in establishing adaptive immunity, they constitute promising targets for immunotherapy. Monocytes can differentiate into DCs in vitro in the presence of colony-stimulating factor 2 (CSF2) and interleukin 4 (IL4), activating four signalling pathways (MAPK, JAK/STAT, NFKB and PI3K). However, the downstream transcriptional programme responsible for DC differentiation from monocytes (moDCs) remains unknown. By analysing the scientific literature on moDC differentiation, we established a preliminary logical model that helped us identify missing information regarding the activation of genes responsible for this differentiation, including missing targets for key transcription factors (TFs). Using ChIP-seq and RNA-seq data from the Blueprint consortium, we defined active and inactive promoters, together with differentially expressed genes in monocytes, moDCs and macrophages, which correspond to an alternative cell fate. We then used this functional genomic information to predict novel targets for previously identified TFs. By integrating this information, we refined our model and recapitulated the main established facts regarding moDC differentiation. Prospectively, the resulting model should be useful to develop novel immunotherapies targeting moDCs. CI - (c) 2021 The Authors. FAU - Nunez-Reza, Karen J AU - Nunez-Reza KJ AUID- ORCID: 0000-0002-5459-8461 AD - Laboratorio Internacional de Investigacion sobre el Genoma Humano, Universidad Nacional Autonoma de Mexico, Juriquilla, Mexico. FAU - Naldi, Aurelien AU - Naldi A AD - Computational Systems Biology team, Institut de Biologie de l'Ecole Normale Superieure, Inserm, CNRS, Universite PSL, Paris, France. FAU - Sanchez-Jimenez, Arantza AU - Sanchez-Jimenez A AUID- ORCID: 0000-0001-9572-2951 AD - Laboratorio Internacional de Investigacion sobre el Genoma Humano, Universidad Nacional Autonoma de Mexico, Juriquilla, Mexico. FAU - Leon-Apodaca, Ana V AU - Leon-Apodaca AV AD - Laboratorio Internacional de Investigacion sobre el Genoma Humano, Universidad Nacional Autonoma de Mexico, Juriquilla, Mexico. FAU - Santana, M Angelica AU - Santana MA AD - Centro de Investigacion en Dinamica Celular (IICBA), Universidad Autonoma del Estado de Morelos, Cuernavaca, Mexico. FAU - Thomas-Chollier, Morgane AU - Thomas-Chollier M AD - Computational Systems Biology team, Institut de Biologie de l'Ecole Normale Superieure, Inserm, CNRS, Universite PSL, Paris, France. FAU - Thieffry, Denis AU - Thieffry D AD - Computational Systems Biology team, Institut de Biologie de l'Ecole Normale Superieure, Inserm, CNRS, Universite PSL, Paris, France. FAU - Medina-Rivera, Alejandra AU - Medina-Rivera A AD - Laboratorio Internacional de Investigacion sobre el Genoma Humano, Universidad Nacional Autonoma de Mexico, Juriquilla, Mexico. LA - eng SI - figshare/10.6084/m9.figshare.c.5428716 PT - Journal Article DEP - 20210611 PL - England TA - Interface Focus JT - Interface focus JID - 101531990 PMC - PMC8193469 OTO - NOTNLM OT - dendritic cells OT - differentiation OT - logical modelling OT - regulatory networks EDAT- 2021/06/15 06:00 MHDA- 2021/06/15 06:01 PMCR- 2021/06/11 CRDT- 2021/06/14 09:43 PHST- 2021/04/15 00:00 [accepted] PHST- 2021/06/14 09:43 [entrez] PHST- 2021/06/15 06:00 [pubmed] PHST- 2021/06/15 06:01 [medline] PHST- 2021/06/11 00:00 [pmc-release] AID - rsfs20200061 [pii] AID - 10.1098/rsfs.2020.0061 [doi] PST - epublish SO - Interface Focus. 2021 Jun 11;11(4):20200061. doi: 10.1098/rsfs.2020.0061. eCollection 2021 Jun.