Affiliation: Johns Hopkins Medicine

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Affiliation: University of California, Davis

Talk Title: Dynamic Shifts: Unraveling Cell Adhesion Changes in Neural Crest EMT 

Abstract: Neural crest cells are vertebrate-specific, pluripotent, embryonic stem cells that give rise to more than 30 different adult cell and tissue types including pigment cells, craniofacial bone and cartilage, and the peripheral nervous system. Despite our extensive knowledge of the mechanisms governing neural crest development, which is primarily derived from a limited set of model organisms, there remains a crucial gap in confirming the functional conservation of protein functions across species, encompassing their targets, interactions, and developmental roles. This challenge impedes a comprehensive understanding of neural crest evolution and development. Our research aspires to bridge this gap by identifying both conserved and divergent developmental mechanisms regulating neural crest EMT. We achieve this goal by characterizing the spatiotemporal expression patterns of key regulatory factors governing neural crest cell development and by perturbing these factors in quail (Coturnix japonica) and chick (Gallus gallus) embryos. Our findings reveal intriguing distinctions in the roles played by specific transcription factors, and conservation of post-translational protein trafficking mechanisms, at various developmental stages within closely related organisms. Moving forward, our focus will shift towards unraveling the intricate embryonic microenvironments responsible for shaping these distinct phenotypic outcomes. By investigating the factors influencing neural crest cell development across species, we aim to enrich our understanding of the evolutionary and developmental dynamics underlying this critical biological process. 

Affiliation: University of California, San Francisco

Talk Title: Spatially controlled RNA decay drives a developmental EMT program 

Abstract: The epithelial-mesenchymal transition (EMT) drives cellular movements during development to create specialized tissues and structures in the vertebrate embryo. Neural crest cells, a multipotent stem cell population, undergo a tightly regulated EMT to delaminate from the neural tube and initiate migration. We have shown that avian neural crest development is controlled by a transient pulse of Draxin, which acts as a molecular rheostat of canonical Wnt signaling. Tight spatiotemporal regulation of Draxin expression is essential for proper neural crest development, and its rapid downregulation is a hallmark of EMT. However, precisely how Draxin transcripts are regulated to ensure their rapid removal has been unclear. To tackle this question, we adapted in vivo reporters and a live RNA imaging approach and found that the rapid degradation of Draxin mRNA is mediated post-transcriptionally via its 3’-untranslated region (3’-UTR). Hybridization chain reaction (HCR) and immunolabeling combined with in situ super-resolution imaging revealed that endogenous Draxin transcripts are targeted to cytoplasmic processing bodies (P-bodies), which are membrane-less sites of RNA processing and decay. Through time-lapse imaging, we found Draxin mRNA not only co-localizes with a fluorescently-tagged P-body component (DCP1a), but is also rapidly dissolved within P-bodies in migrating neural crest cells. Furthermore, knockdown of the RNA helicase DDX6 via CRISPR/Cas9, known to dissolve P-bodies, disrupted compartmentalization of Draxin mRNA to P-bodies. Importantly, disruption of P-bodies via DDX6 knockdown inhibited endogenous Draxin mRNA degradation and impeded neural crest EMT in vivo. This is consistent with observations in human patients who display defects in P-body assembly and often present with craniofacial abnormalities, a hallmark of neural crest dysfunction. This work provides the first description of P-bodies in vertebrate neural crest through super-resolution imaging and an adapted RNA live imaging approach, and identifies an mRNA that is targeted to and degraded within P-bodies. Together, our data highlight a novel and important role for spatial regulation of gene expression during development— playing an essential role in neural crest EMT via targeted RNA decay. 

Affiliation: The Francis Crick Institute

Talk Title: TBA

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Affiliation: Instituto de Neurosciencias, CSIC-UMH

Talk Title: EMT trajectories in development, fibrosis and cancer 

Abstract: Epithelial homeostasis is crucial for maintaining tissue architecture and must therefore be tightly regulated in the adult. In contrast, embryonic cells show a high degree of epithelial plasticity necessary for proper morphogenesis and, in particular, for the massive cell movements that occur during gastrulation and neural crest delamination, among other processes. We have studied cell movements, plasticity, and epithelial-to-mesenchymal transitions (EMTs) in different contexts. Lineage tracing and single-cell transcriptomics have allowed us to reveal how EMT programs are implemented along cellular plasticity trajectories in three different settings, namely neural crest, renal fibrosis and breast cancer. For breast cancer, our data unveil a new role for the EMT in orchestrating an additional layer of intratumour heterogeneity, driving the distribution of functions associated with either inflammation or cancer cell dissemination towards metastasis. 

Affiliation: University of Cambridge, California Institute of Technology

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Abstract: TBA

Affiliation: University of Pittsburgh

Talk Title: Data-driven mechanistic modeling of EMT regulation 

Abstract: High-throughput techniques, especially at the single cell level, have greatly expanded our knowledge of cellular processes. With the increasing availability of data, a fundamental question arises: how can we leverage this data to gain mechanistic insights? Unlike static data typically targeted by statistics-based machine learning approaches, single cell data are snapshots from the dynamical state space of a cell having interacting components that dictate the temporal evolution of the system. Consequently, we witness a growing convergence of two disciplines: data science and systems biology. The latter seeks to unravel qualitative and quantitative causal relationships among cellular components, as well as their functions within the broader context of cell regulatory networks, all through the lens of dynamical systems theory, towards a goal of engineering and controlling cell state transition dynamics. I will briefly summarize some of our recent efforts on analyzing single cell data through the lens of systems biology. Specifically, I will present our recent efforts of applying single cell snapshot and live cell imaging data analyses on EMT regulation. 

Affiliation: Indian Institute of Science, Bangalore

Talk Title: Epigenetic memory acquired during long-term EMT induction governs the recovery to the epithelial state 

Abstract: Epithelial-mesenchymal transition (EMT) and its reverse mesenchymal-epithelial transition (MET) are critical during embryonic development, wound healing and cancer metastasis. While phenotypic changes during short-term EMT induction are reversible, long-term EMT induction has been often associated with irreversibility. Here, we show that phenotypic changes seen in MCF10A cells upon long-term EMT induction by TGFβ need not be irreversible, but have relatively longer time scales of reversibility than those seen in short-term induction. Next, using a phenomenological mathematical model to account for the chromatin-mediated epigenetic silencing of the miR-200 family by ZEB family, we highlight how the epigenetic memory gained during long-term EMT induction can slow the recovery to the epithelial state post-TGFβ withdrawal. Our results suggest that epigenetic modifiers can govern the extent and time scale of EMT reversibility and advise caution against labelling phenotypic changes seen in long-term EMT induction as ‘irreversible’. 

Affiliation: The University of Queensland

Talk Title: Tissue mechanics, mechanotransduction and homeostasis 

Abstract: Epithelia constitute many of the principal barriers in metazoan bodies and are also common sites for disease, notably cancer and inflammation. Yet, the incidence of epithelial disease is remarkably low, given their constant exposure to injurious agents. By implication, epithelia must have ways to detect potential disturbances and deal with them. It is now becoming apparent that one basis for such homeostatic response is through tissue mechanics and mechanosensing. Cells constantly exert contractile forces on their neighbours through their cell-cell junctions and possess mechanotransduction pathways at those junctions that detect changes in force. Mechanosensing may then be an early-warning system that allows epithelia to detect, and respond to, homeostatic challenges. Can physiological homeostasis reflect mechanical homeostasis? Conversely, can altered tissue mechanics predispose epithelia to disease? These are ideas that I’ll endeavour to consider in my talk. 

Affiliation: Weselayn University

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Abstract: TBA

Affiliation: The University of Sheffield

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Abstract: TBA

Affiliation: MRC-Laboratory of Molecular Biology

Talk Title: Mechanisms of human renal mesenchymal-to-epithelial transition 

Abstract: During embryogenesis, organs form through the transformation of simple groups of cells into complex 3D structures. This remarkable feat is accomplished through the collective and controlled changes in the shapes and arrangements of a large number of cells. The central aim of my group is to understand how genetic programmes drive morphological changes in individual cells, and how those shape changes are coordinated through cell-cell interactions across an entire epithelium to sculpt a nascent tissue. Because organ shape is critical for organ function, defects in morphogenesis lead to severe diseases including spina bifida or polycystic kidney disease. We use human renal organoids derived from iPSCs to understand how de novo epithelial polarisation, or mesenchymal-to-epithelial transition, occurs in the context of nephron tube morphogenesis, what transcriptional blueprint is required to kick-start the process and what molecular players drive the cell biological changes. I will discuss our recent findings addressing these questions. 

Affiliation: Memorial Sloan Kettering Cancer Center

Talk Title: Building the endoderm through widespread intercalation 

Abstract: TBA