High Dimensional Single-Cell Analysis Reveals iNKT Cell Developmental Trajectories and Effector Fate Decision - Archive ouverte HAL Access content directly
Journal Articles Cell Reports Year : 2020

High Dimensional Single-Cell Analysis Reveals iNKT Cell Developmental Trajectories and Effector Fate Decision

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Carolina de Amat Herbozo

Abstract

CD1d-restricted invariant Natural Killer T (iNKT) cells represent a unique class of T lymphocytes endowed with potent regulatory and effector immune functions. Although these functions are acquired during thymic ontogeny, the sequence of events that gives rise to discrete effector subsets remains unclear. Using an unbiased single-cell transcriptomic analysis combined with functional assays, we reveal an unappreciated diversity among thymic iNKT cells, especially among iNKT1 cells. Mathematical modeling and biological methods unravel a developmental map whereby iNKT2 cells constitute a transient branching point toward the generation of iNKT1 and iNKT17 cells, which reconciles the two previously proposed models. In addition, we identify the transcription co-factor Four-and-a-half LIM domains protein 2 (FHL2) as a critical cell-intrinsic regulator of iNKT1 specification. Thus, these data illustrate the changing transcriptional network that guides iNKT cell effector fate.
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Dates and versions

hal-03365048 , version 1 (14-01-2022)

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Thomas Baranek, Kevin Lebrigand, Carolina de Amat Herbozo, Loïc Gonzalez, Gemma Bogard, et al.. High Dimensional Single-Cell Analysis Reveals iNKT Cell Developmental Trajectories and Effector Fate Decision. Cell Reports, 2020, 32 (10), pp.108116. ⟨10.1016/j.celrep.2020.108116⟩. ⟨hal-03365048⟩
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