RT Journal Article SR Electronic T1 Deciphering the Regulatory Landscape of γδ T Cell Development by Single-Cell RNA-Sequencing JF bioRxiv FD Cold Spring Harbor Laboratory SP 478529 DO 10.1101/478529 A1 Sagar A1 Maria Pokrovskil A1 Josip S. Herman A1 Shruti Naik A1 Elisabeth Sock A1 Ute Lausch A1 Michael Wegner A1 Yakup Tanriver A1 Dan R. Littman A1 Dominic Grün YR 2018 UL http://biorxiv.org/content/early/2018/11/27/478529.1.abstract AB Recent studies have established γδ T cells as critical players in a broad range of infections, antitumor surveillance, autoimmune diseases and tissue homeostasis. However, differentiation of γδ T cells in the adult thymus remains poorly understood, due to the rare frequency of this lineage. Here, we infer high-resolution developmental trajectories of this rare population by single-cell RNA-sequencing. We reveal previously unknown subtypes and identify the transcription factor c-MAF as a novel key regulator of IL-17-producing γδ T cell (γδT17) differentiation. c-MAF knockout mice exhibit a complete block in γδT17 differentiation, absence of these cells from peripheral organs, and protection from an autoimmune phenotype in a psoriasis model. Single-cell RNA-sequencing of Sox13 and Rorc knockout mice pinpoints c-MAF as an essential missing link between these lineage-specifying factors. These findings significantly enhance our understanding of γδ T cell ontogeny. Our experimental strategy provides a blueprint for deciphering differentiation of rare cell types.