Deciphering the Regulatory Landscape of <i>γδ</i> T Cell Development by Single-Cell RNA-Sequencing

Sagar, Sagar; Pokrovskil, Maria; Herman, Josip Stefan; Naik, Shruti; Sock, Elisabeth; Lausch, Ute; Wegner, Michael; Tanriver, Yakup; Littman, Dan R.; Grün, Dominic

doi:10.1101/478529

Cited by 3 publications

(2 citation statements)

References 58 publications

(66 reference statements)

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“…Interestingly, although CD24 + γδ thymocytes are considered "immature, " they nonetheless express key TFs necessary for their effector acquisition, such as RORγt for Tγδ17 cells (49,54,55), and are surprisingly also functionally competent to produce IL-17A (51). The application of global single cell transcriptomic analysis to fetal γδ thymocytes is likely to add significant granularity to the developmental trajectories of effector programming [preprint (56)].…”

Section: Effector Diversification Of γδ Thymocytesmentioning

confidence: 99%

Regulation of γδ T Cell Effector Diversification in the Thymus

Parker

Ciofani

2020

Front. Immunol.

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γδ T cells are the first T cell lineage to develop in the thymus and take up residence in a wide variety of tissues where they can provide fast, innate-like sources of effector cytokines for barrier defense. In contrast to conventional αβ T cells that egress the thymus as naïve cells, γδ T cells can be programmed for effector function during development in the thymus. Understanding the molecular mechanisms that determine γδ T cell effector fate is of great interest due to the widespread tissue distribution of γδ T cells and their roles in pathogen clearance, immunosurveillance, cancer, and autoimmune diseases. In this review, we will integrate the current understanding of the role of the T cell receptor, environmental signals, and transcription factor networks in controlling mouse innate-like γδ T cell effector commitment.

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Section: Effector Diversification Of γδ Thymocytesmentioning

confidence: 99%

Regulation of γδ T Cell Effector Diversification in the Thymus

Parker

Ciofani

2020

Front. Immunol.

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“…Thus, thymic development of γδT17 is dependent on the consecutive expression of the transcription factors Sox13, cMAF followed by the lineage defining expression of RORγt. Conversely, the IFNγ producing γδT cells are characterized by the transcription factors Tbet and Tcf1 (Sagar et al, 2018;Zuberbuehler et al, 2019). Further, canonical and non-canonical NF-κB pathway signaling in the thymic microenvironment are essential for the development of γδT17.…”

Section: Introductionmentioning

confidence: 99%

The cIAP ubiquitin ligases sustain type 3 γδ T and innate lymphoid cells during aging to allow normal cutaneous and mucosal responses

Rizk

Mörbe

Agerholm

et al. 2020

Preprint

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AbstractRORγt+ γδ T cells, known as γδT17, are an innate-like subset of T cells that produce interleukin (IL)-17A and initiate type 3 immune responses during infections or autoimmune pathologies. Herein we show that the cellular inhibitor of apoptosis proteins cIAP1 and 2 are required for the peripheral homeostasis of γδT17 but not for their thymic development. γδT17 cells that were deficient in both cIAP1 and 2 were profoundly reduced in the peripheral lymph nodes and skin. Likewise, both RORγt+ innate lymphoid cells (ILC3) and RORγt+ Tbet+ γδ T cells were reduced in the lamina propria of adult mice. Further, cIAP1 and 2 were required for the expression of the transcription factors RORγt and cMAF in γδT17 cells during neonatal and adult life. Single deficiency of either cIAP1 or 2 did not affect the homeostasis or transcription factor profile of γδT17 cells. Moreover, bone marrow reconstitutions and transfer of neonatal γδ T cells to RAG1−/− hosts showed that both intrinsic and extrinsic factors contribute to the loss of γδT17 cells in cIAP1/2 double deficient mice, while only extrinsic signals were responsible for the decrease of ILC3 cells. Deficiency of γδT17 cells in cIAP1 and cIAP2 double deficient animals, or the presence of functionally defective γδT17 cells did not confer protection against IMQ-induced psoriasis. Collectively, our data reveal a previously undescribed role for cIAP1 and cIAP2 in the homeostasis of γδT17 and ILC3 cells.

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Joint probabilistic modeling of paired transcriptome and proteome measurements in single cells

Gayoso

Steier²,

Lopez

et al. 2020

Preprint

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The paired measurement of RNA and surface protein abundance in single cells with CITE-seq is a promising approach to connect transcriptional variation with cell phenotypes and functions. However, each data modality exhibits unique technical biases, making it challenging to conduct a joint analysis and combine these two views into a unified representation of cell state. Here we present Total Variational Inference (totalVI), a framework for the joint probabilistic analysis of paired RNA and protein data from single cells. totalVI probabilistically represents the data as a composite of biological and technical factors such as limited sensitivity of the RNA data, background in the protein data, and batch effects. To evaluate totalVI, we performed CITE-seq on immune cells from murine spleen and lymph nodes with biological replicates and with different antibody panels measuring over 100 surface proteins. With this dataset, we demonstrate that totalVI provides a cohesive solution for common analysis tasks like the integration of datasets with matched or unmatched protein panels, dimensionality reduction, clustering, evaluation of correlations between molecules, and differential expression testing. totalVI enables scalable, end-to-end analysis of paired RNA and protein data from single cells and is available as open-source software.

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Deciphering the Regulatory Landscape of γδ T Cell Development by Single-Cell RNA-Sequencing

Cited by 3 publications

References 58 publications

Regulation of γδ T Cell Effector Diversification in the Thymus

Regulation of γδ T Cell Effector Diversification in the Thymus

The cIAP ubiquitin ligases sustain type 3 γδ T and innate lymphoid cells during aging to allow normal cutaneous and mucosal responses

Joint probabilistic modeling of paired transcriptome and proteome measurements in single cells

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