Abstract

Please come along to the monthly campus Single Cell Seminar series. All are welcome, include colleagues from Cambridge (though email me so we can book them in as a visitor with security). This month we have two exciting talks.

1) Felipe Viera Braga (Teichmann lab)

2) Jeanette Baran-Gale (Ponting lab, Edinburgh)

Felipe’s talk: “Tackling Asthma remission one cell at a time”

The lungs are a primary site of allergic reactions and viral infections. Asthma is an inflammatory disease characterized by uncontrolled inflammatory response in the lungs. Despite its high prevalence in the human population, a large proportion of the patients undergo natural asthma remission over time. The molecular mechanisms behind remission are unknown. CD4 T cells play a central role in the lung immune response characteristic of asthma. In order to investigate a putative role of CD4 T cells in asthma remission, we established a protocol to isolate CD4 T cells from lung biopsies of healthy volunteers, active asthma, clinical remission and complete remission patients. We used single cell transcriptomics to obtain the maximum amount of information, whilst conserving their biological diversity. Preliminary analysis led to the identification of disease specific cell clusters characterized by specific markers and pathways. Our data establish a unique single cell transcriptomic atlas of healthy and asthmatic lung CD4 T cells, whilst suggesting putative molecular mechanisms involved in asthma remission.

Jeanette’s talk: “Promiscuous gene expression in single medullary thymic epithelial cells + highlights from ISMB /ECCB 2017” In the thymus, medullary thymic epithelial cells (mTECs) present self-antigens to passing thymocytes in a process known as negative selection, whereby thymocytes that strongly react to the presented antigen are eliminated. In order to prevent self-reactive thymocytes from leaving the thymus, mTECs collectively express at least 90% of protein coding genes, including those typically restricted to peripheral tissues. This process, known as promiscuous gene expression (PGE), is partially regulated by the autoimmune regulator (Aire). While some tissue-restricted genes (TRGs) are expressed independently of Aire, about 600 TRGs are expressed in an Aire-dependent manner and ~3400 are enhanced by Aire. We aim to uncover patterns in TRG co-expression in individual mTECs by sequencing the individual transcriptomes of mTECs that are unselected or FACS sorted based on cell surface expression of Glycoprotein 2 (Gp2), a pancreatic protein that is promiscuously expressed in mTECs in an Aire-enhanced fashion. We have sequenced two batches of individual mTECs, and together these data provide us with the individual transcriptomes of nearly five thousand mTECs, including about one thousand mTECs that express Gp2 protein. Additionally, I will provide highlights from the ISMB /ECCB 2017 conference in Prague from 21-25 July 2017.