A5014532974- Pluripotent Stem Cells Research
- Wnt/β-catenin signaling in development and cancer
- Developmental Biology and Gene Regulation
- CRISPR and Genetic Engineering
- Single-cell and spatial transcriptomics
- Reproductive Biology and Fertility
- Tissue Engineering and Regenerative Medicine
- Renal and related cancers
- Cell Image Analysis Techniques
- Gene Regulatory Network Analysis
- Cancer-related gene regulation
- Hippo pathway signaling and YAP/TAZ
- Birth, Development, and Health
- Cellular Mechanics and Interactions
- RNA Research and Splicing
- Lysosomal Storage Disorders Research
- Pancreatic function and diabetes
- Advanced Fluorescence Microscopy Techniques
- Silk-based biomaterials and applications
- 3D Printing in Biomedical Research
- Genomics and Chromatin Dynamics
- Parkinson's Disease Mechanisms and Treatments
- Cancer-related molecular mechanisms research
- Nuclear Receptors and Signaling
- Global Health and Surgery
Universidad de Las Palmas de Gran Canaria
2018-2025
University of Würzburg
2023
University of Bath
2013-2022
Kettering University
2013-2014
University of Cambridge
2009-2014
Memorial Sloan Kettering Cancer Center
2013
Universitat de València
2005-2007
There is evidence that pluripotency of mouse embryonic stem (ES) cells associated with the activity a network transcription factors Sox2, Oct4, and Nanog at core. Using fluorescent reporters for expression Nanog, we observed population ES best described by dynamic distribution characterized two peaks defined high (HN) low (LN) expression. Typically, LN state 5%-20% total population, depending on culture conditions. Modelling reveals simple Oct4/Sox2 can account its properties as long...
The transcription factor Oct4 is required in vitro for establishment and maintenance of embryonic stem cells reprogramming somatic to pluripotency. In vivo, it prevents the ectopic differentiation early embryos into trophoblast. Here, we further explore role blastocyst formation specification epiblast versus primitive endoderm lineages using conditional genetic deletion. Experiments involving mouse deficient both maternal zygotic suggest that dispensable zygote formation, cleavage activation...
The maintenance of pluripotency in mouse embryonic stem cells (mESCs) relies on the activity a transcriptional network that is fuelled by three transcription factors (Nanog, Oct4 and Sox2) balanced repressive Tcf3. Extracellular signals modulate regulate differentiation capacity cells. Wnt/β-catenin signaling has emerged as significant potentiator pluripotency: increases levels β-catenin Nanog, enhance pluripotency. A recent report shows achieves some these effects modulating Tcf3, this...
Highlights•Software for automated 2D/3D nuclear segmentation of image data•Identification nuclei, with links to information on position•Quantitative fluorescence data each channel•Computational identification inner versus outer cells in preimplantation embryosSummarySegmentation is a fundamental problem that dominates the success microscopic analysis. In almost 25 years cell detection software development, there still no single piece commercial works well practice when applied early mouse...
Notch receptors act as ligand-dependent membrane-tethered transcription factors with a prominent role in binary cell fate decisions during development, which is conserved across species. In addition there increasing evidence for other functions of Notch, particularly connection Wnt signalling: able to modulate the activity Armadillo/ß-catenin, effector signalling, manner that independent its transcriptional activity. Here we explore mechanism this interaction epithelium Drosophila imaginal...
The pluripotent state is traditionally associated with large absolute levels of certain transcription factors such as Nanog and Oct4. Here, we present experimental observations using quantitative immunofluorescence that pluripotency in mouse embryonic stem cells (mESCs) established by specific ratios between Oct4 Nanog. When are grown 2i conditions, they exhibit uniform this a high correlation the individual cells. lost when differentiate. Our results suggest these two distribution...
Due to the large amount of data produced by advanced microscopy, automated image analysis is crucial in modern biology. Most applications require reliable cell nuclei segmentation. However, many biological specimens are densely packed and appear touch one another images. Therefore, a major difficulty three-dimensional segmentation decomposition that apparently each other. Current methods highly adapted certain specimen or specific microscope. They do not ensure similarly accurate...
Cell fate choice is a key event happening during preimplantation mouse development. From embryonic day 3.5 (E3.5) to E4.5, the inner cell mass (ICM) differentiates into epiblast (Epi, NANOG expressing cells) and primitive endoderm (PrE, GATA6, SOX17 and/or GATA4 cells). The mechanism by which ICM cells differentiate Epi PrE remains partially unknown. FGF/ERK has been proposed as main signalling pathway for this event, but it does not explain co-expression of GAT6 or how initiated. In study,...
Abstract The activity of Wnt and Notch signalling is central to many cell fate decisions during development the maintenance differentiation stem populations in homeostasis. While classical views refer these pathways as independent signal transduction devices that co‐operate different systems, recent work has revealed intricate connections between their components. These observations suggest rather than operating two separate pathways, elements configure an integrated molecular device whose...
Pluripotency in embryonic stem cells is maintained through the activity of a small set transcription factors centred around Oct4 and Nanog, which control expression ‘self‐renewal’ ‘differentiation’ genes. Here, we combine single‐cell quantitative immunofluorescence microscopy gene analysis, together with theoretical modelling, to investigate how those regulated. We uncover key role for post‐translational regulation maintenance pluripotency, complements well‐established transcriptional...
During mammalian preimplantation, cells of the inner cell mass (ICM) adopt either an embryonic or extraembryonic fate. This process is tightly regulated in space and time has been studied previously mouse embryos stem models. Current research suggests that fates are arranged a salt-and-pepper pattern random positioning spatially alternating pattern. However, details three-dimensional patterns fate specification have not investigated embryo nor vitro systems. We developed ICM organoids as a,...
During mammalian blastocyst development, inner cell mass (ICM) cells differentiate into epiblast (Epi) or primitive endoderm (PrE). These two fates are characterized by the expression of transcription factors NANOG and GATA6, respectively. Here, we investigate spatio-temporal distribution GATA6 expressing in ICM mouse blastocysts with quantitative three-dimensional single cell-based neighbourhood analyses. We define local features, which include levels both fate markers expressed each its...
There is increasing evidence for close functional interactions between Wnt and Notch signalling. In many instances, these are mediated by convergence of the signalling events on common transcriptional targets, but there other instances that cannot be accounted in this manner. Studies Drosophila have revealed an activated form Armadillo, effector signalling, interacts with, modulated by, receptor. Specifically, ligand-independent traffic serves to set up a threshold amount Armadillo therefore...
Here we investigate the structural and functional basis of interactions between Notch Wingless signalling in Drosophila. Using yeast-two-hybrid pull-down assays show that can bind directly a form Dishevelled is stabilized upon signalling. Moreover, mechanism by which able to downregulate promoting its ligand-independent traffic compartment where it degraded this activity depends on Dishevelled.
Initial genetic studies in Drosophila suggested that several members of the Rho subfamily (RhoA, Rac1 and Cdc42) are involved planar cell polarity (PCP) establishment. However, analyses Rac1, Rac2 Mtl loss-of-function (LOF) mutants have argued against their role this process. Here, we investigate detail GTPases Mtl, Cdc42, PCP generation. These functional were performed by overexpressing eyes wings, performing interaction assays using a combination triple quadruple mutant LOF clones. We...
Central nervous system-expressed long non-coding RNAs (lncRNAs) are often located in the genome close to protein coding genes involved transcriptional control. Such lncRNA-protein gene pairs frequently temporally and spatially co-expressed system predicted act together regulate neuronal development function. Although some of these lncRNAs also bind modulate activity encoded transcription factors, regulatory mechanisms controlling co-expression neighbouring remain unclear. Here, we used high...