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Download Abstract book - SciLifeLab Science Summit 2016
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Abstracts Science Summit 2016 John Marioni, EMBL-EBI, Sanger Institute & CRUK Cambridge Institute, United Kingdom -‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐ Understanding early mammalian development using single-cell transcriptomics Gastrulation and the specification of the three germ layers are key events in animal development. However, molecular analyses of these processes have been limited due to the small number of cells present in gastrulating embryos. With recent developments in the field of single-cell biology however, it is now possible to overcome these limitations and to characterize, for the first time at the single-cell level, how cell fate decisions are made. In this presentation I will discuss data generated to study cell fate specification in mouse, as well as the computational strategies we have developed to model such data. I will then illustrate how these data can provide insight into germ layer specification and early erythropoiesis. Barbara Treutlein Max Planck Institute for Evolutionary Anthropology & Molecular Cell Biology and Genetics, Germany -‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐ Dissecting human cerebral organoids and fetal neocortex using single-cell RNA-seq Cerebral organoids – three-dimensional cultures of human cerebral tissue derived from pluripotent stem cells – have emerged as models of human cortical development. However, the extent to which in vitro organoid systems recapitulate neural progenitor cell proliferation and neuronal differentiation programs observed in vivo remains unclear. Here we use single-cell RNA sequencing (scRNA-seq) to dissect and compare cell composition and progenitor-to-neuron lineage relationships in human cerebral organoids and fetal neocortex. Covariation network analysis using the fetal neocortex data reveals known and novel interactions among genes central to neural progenitor proliferation and neuronal differentiation. In the organoid, we detect diverse progenitors and differentiated cell types of neuronal and mesenchymal lineages, and identify cells that derived from regions resembling the fetal neocortex. We find that these organoid cortical cells use gene expression programs remarkably similar to those of the fetal tissue in order to organize into cerebral cortex-like regions. Our comparison of in vivo and in vitro cortical single cell transcriptomes illuminates the genetic features underlying human cortical development that can be studied in organoid cultures. Igor Adamyenko Medical University of Vienna, Austria & Karolinska Institutet -‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐ Single cell transcriptomics for resolving neural crest populations and for solving the challenge of crest multipotency Neural crest cells are very important embryonic progenitors that are responsible for organising the face and also building peripheral nervous system. Current estimates agree on that these multipotent and migratory cells can give rise to around 100 different cell types in the body. It is not clear, how early neural crest cells commit to a certain fate and how fate restrictions and switches are implemented. We took advantage of single cell transcriptomics approach to address the diversity of pre-migratory and migratory neural crest. In result we found that many crest cells commit to neuronal and some other fates already at the level of the neural tube while the other neural crest cells make this choice much later. We also likely found a population of crest cells that are derived from the new specialized regions not related directly to the neural tube. During the talk I will discuss the identified populations and show the comparison between the cranial crest (producing mostly the tissues of the face) and the trunk crest (generating mostly peripheral nervous system). Sten Linnarsson Karolinska Institutet/SciLifeLab -‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐ Single-cell RNA-seq in the mammalian brain The brain is arguably the most complex organ in all biology. To understand how it works, at a minimum, we need to learn how it’s built: what are the components, how are they connected, and how do they talk to each other? With the recent development of single-cell RNA-seq, it has become increasingly feasible to map the cell types of the brain without the use of predefined markers. With the aim of ultimately revealing the molecular anatomy of the whole mouse brain, we have performed pilot experiments on ten selected regions. We found hundreds of molecularly distinct cell types, including neurons, glia and vascular cells. Neuronal diversity greatly exceeds that of glia and other cell types, and particular regions are especially diverse (e.g. hypothalamus). Interestingly, molecular similarity largely conforms to developmental lineage ancestry. We discuss the implications of these findings, as well as the prospects of generating a complete molecular atlas of the brain. Maria Kasper Karolinska Institutet -‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐ Single-cell transcriptomics resolves heterogeneity of murine epidermis and hair follicles The murine epidermis with its hair follicles represents one of the most important model systems for studying adult stem cells and tissue regeneration. Here we used single-cell RNA-seq to reveal how cellular heterogeneity of murine epidermis is tuned at the transcriptional level. Unbiased clustering of 1422 single-cell transcriptomes revealed 25 distinct populations of epidermal cells. Moreover, the single-cell data allowed for unprecedented reconstruction of the gene expression program during epidermal differentiation and, for the first time, of a spatial axis. Intriguingly, we found that transcriptional heterogeneity of the epidermis can essentially be explained along these two dimensions, and heterogeneity in the stem cell compartment generally reflects this model: stem cell populations are segregated by spatial signatures but share a common basal epidermal gene module. This study provides the first unbiased and systematic view of transcriptional organization of adult mammalian epidermis and highlights how cellular heterogeneity can be orchestrated to assure tissue homeostasis. Fabien Burki Uppsala University/SciLifeLab -‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐ Promises and challenges of single-cell genomics in microbial eukaryotes Single-cell genomics, including transcriptomics, pioneered in medical research. Lately, the application of these approaches also in microbial research has been seen as the new frontier to a comprehensive understanding of genomics, cell biology, ecology, and evolution of uncultured species. Whilst breakthroughs are being made on a regular basis, many challenges remain in particular in the case of complex unicellular eukaryote genomes that lack close reference. In this presentation, I will first show why accessing the genome of the uncultured majority of microbial eukaryote diversity is essential, and then discuss our own experience on single-cell analyses. As with most new methods, single-cell genomics on microbial eukaryotes present great promises and many challenges, none that cannot be addressed but all that should be considered. John Tsang National Institute of Allergy and Infectious Diseases, NIH, USA -‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐ From single cells to networks to human populations: assessing and utilizing heterogeneity of the immune system My lab works on developing and applying systems approaches— combining computation, modeling and experiments—to study the immune system at both the organismal and cellular levels. Heterogeneity—from cell-to-cell variations to spatial heterogeneity to differences among human individuals—is a hallmark of the immune system. In this talk, I will highlight efforts in the lab for studying and utilizing such heterogeneities to assess information propagation in immune cellular networks and uncover functional correlates of cell-to-cell variation in humans. Using human macrophage activation as a model, I will illustrate how single- and k-cell profiling of cell-to-cell expression variation (CEV) enables robust inference of condition-specific rewiring of and information propagation in gene regulatory networks. Our analysis uncovered a condition-specific signaling and transcriptional circuit that underlies the macrophage response to Interleukin (IL)-10 and revealed how variation in gene expression can be propagated in a condition dependent manner within cells. Next I will discuss time-resolved quantification of CEV in distinct immune cell subsets in a human cohort and how such a population-based approach can reveal functional correlates of CEV, including examples linking CEV to human aging and genetic variants associated with disease. Funded in part by Intramural Program of NIAID/NIH. Rachel Foster Stockholm University -‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐ Single cell imaging of microbial populations important to N and C cycling in Open Ocean Ecosystems Major foci in the field of microbiology are to determine: what organisms are present, what they are doing, and how they interact with each other and the environment. Using a high resolution nanometer scale secondary ion mass spectrometry (nanoSIMS) approach on marine planktonic (field) populations important to nitrogen (N) and carbon (C) cycling, we have begun to identify great variation in single cell assimilation activities, novel interactions (e.g. new symbioses) and metabolic strategies, which would otherwise be diluted or difficult to recognize using standard bulk approaches. Single cell imaging and observations can therefore provide subtle insights of microbial populations and are directly applicable to biogeochemical models for predicting nutrient cycling in ecosystems. A suite of examples using nanoSIMS to image and quantify the activity of microorganisms important to N and C cycling from the marine environment, including free-living and planktonic N2 fixing cyanobacteria and Achaea and eubacteria attached to marine snow particles, will be presented and discussed.
