Project #7046
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#7046 : Transcriptional regulation of innate lymphoid cell plasticity versus differentiation
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Name of Applicant : Rachel GOLUB
Date of application : 06-09-2016
Unit : Lymphopoiesis
Location : Metchnikoof-5th Floor-Room 5006
Phone : 0145688766
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Project context and summary :

Over the last years, innate lymphoid cells (ILC) have been increasingly investigated. Despite the absence of antigen specific receptors, they belong to the lymphoid lineage and represent important sentinels for tissue homeostasis and inflammation. They contribute to numerous homeostatic and pathophysiological situations via specific cytokine production. ILC are currently divided into three groups based on the expression of specific transcription factors and secretion of cytokines. We focus this study on fetal ILC3 development. We have observed that contrary to lymphocytes, ILC can migrate toward lymphoid organs, tissues and mucosal sites as lymphoid precusors and terminate their developmental program in situ. In the fetal spleen, we observe different stages of ILC3 with precursors that are already RORgt+ but could still give rise to other ILC fate. Hence, these splenic ILC3 precursors were sorted and analyzed by microarrays. The identification of gene expression differences was used to design a single cell transcriptomic assay. The single cell transcriptomic assay is based on this specific selection of primers for transcription factors and cytokine receptors. We evaluate their differential expression in single cells at different stages of their plasticity. The aim is to decipher the progression from an ILC precursor stage to an another in one cell. We are also using the new polaris technology to detect and evaluate at different early timepoints the sequence of molecular events for changing ILC cell fate. In this case, we chose to use the sc RNAseq technology. The single cell transcriptomic will be analyzed and bioinformatic programs will be applied in order to organize the sequential molecular events and to build a hierarchical developmental model in case of ILC cell fate decisions.

Related team publications :
Notch signaling in group 3 innate lymphoid cells modulates their plasticity. Sci Signal. 2016 May 3;9(426):ra45.
Single-Cell Gene Expression Analyses Reveal Heterogeneous Responsiveness of Fetal Innate Lymphoid Progenitors to Notch Signaling. Cell Rep. 2016 Feb 16;14(6):1500-16.
Single-cell analysis defines the divergence between the innate lymphoid cell lineage and lymphoid tissue-inducer cell lineage. Nat Immunol. 2016 Mar;17(3):269-76.
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Project Type : Short
Status : In Progress

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