A5002599662- Pluripotent Stem Cells Research
- Gene Regulatory Network Analysis
- CRISPR and Genetic Engineering
- Plant Molecular Biology Research
- Epigenetics and DNA Methylation
- Single-cell and spatial transcriptomics
- Plant Gene Expression Analysis
- Bioinformatics and Genomic Networks
- Renal and related cancers
- Tissue Engineering and Regenerative Medicine
- Genomics and Chromatin Dynamics
- Gene expression and cancer classification
- Plant-Microbe Interactions and Immunity
- Photosynthetic Processes and Mechanisms
- Chromosomal and Genetic Variations
- Genetic Mapping and Diversity in Plants and Animals
- Plant Water Relations and Carbon Dynamics
- RNA Interference and Gene Delivery
- Plant Stress Responses and Tolerance
- Mesenchymal stem cell research
- Prenatal Screening and Diagnostics
- Microbial Metabolic Engineering and Bioproduction
- Platelet Disorders and Treatments
- Animal Genetics and Reproduction
- Birth, Development, and Health
University of Cambridge
2017-2024
Wellcome/MRC Cambridge Stem Cell Institute
2021-2024
Medical Research Council
2021-2024
Wellcome Trust
2017-2023
Wellcome/Cancer Research UK Gurdon Institute
2017-2023
University of Warwick
2011-2021
University of Sheffield
2012
Abstract Leaf senescence is an essential developmental process that impacts dramatically on crop yields and involves altered regulation of thousands genes many metabolic signaling pathways, resulting in major changes the leaf. The complex, although regulatory have been characterized, there little information how these function global control process. We used microarray analysis to obtain a high-resolution time-course profile gene expression during development single leaf over 3-week period...
Abstract Transcriptional reprogramming forms a major part of plant's response to pathogen infection. Many individual components and pathways operating during plant defense have been identified, but our knowledge how these different interact is still rudimentary. We generated high-resolution time series gene expression profiles from single Arabidopsis thaliana leaf infection by the necrotrophic fungal Botrytis cinerea. Approximately one-third genome differentially expressed first 48 h after...
Summary A model is presented describing the gene regulatory network surrounding three similar NAC transcription factors that have roles in Arabidopsis leaf senescence and stress responses. ANAC 019 , 055 072 belong to same clade of domain genes overlapping expression patterns. combination promoter DNA /protein interactions identified using yeast 1‐hybrid analysis modelling time course data has been applied predict upstream these genes. Similarities divergence regulation during a variety...
Inferring the topology of a gene-regulatory network (GRN) from genome-scale time-series measurements transcriptional change has proved useful for disentangling complex biological processes. To address challenges associated with this inference, number competing approaches have previously been used, including examples information theory, Bayesian and dynamic networks (DBNs), ordinary differential equation (ODE) or stochastic equation. The performance these assessed using variety in silico vivo...
Transcriptional reprogramming is integral to effective plant defense. Pathogen effectors act transcriptionally and posttranscriptionally suppress defense responses. A major challenge understanding disease responses discriminating between transcriptional associated with microbial-associated molecular pattern (MAMP)-triggered immunity (MTI) that orchestrated by effectors. high-resolution time course of genome-wide expression changes following Pseudomonas syringae pv tomato DC3000 the...
In Arabidopsis thaliana, changes in metabolism and gene expression drive increased drought tolerance initiate diverse avoidance escape responses. To address regulatory processes that link these responses, we set out to identify genes govern early responses drought. do this, a high-resolution time series transcriptomics data was produced, coupled with detailed physiological metabolic analyses of plants subjected slow transition from well-watered conditions. A total 1815 drought-responsive...
The maternal-to-zygotic transition (MZT) marks the period when embryonic genome is activated and acquires control of development. Maternally inherited factors play a key role in this critical developmental process, which occurs at 2-cell stage mice. We investigated function maternally factor Stella (encoded by Dppa3) using single-cell/embryo approaches. show that loss maternal results widespread transcriptional mis-regulation partial failure MZT. Strikingly, activation endogenous...
Human germline-soma segregation occurs during weeks 2-3 in gastrulating embryos. Although direct studies are hindered, here, we investigate the dynamics of human primordial germ cell (PGCs) specification using vitro models with temporally resolved single-cell transcriptomics and in-depth characterisation vivo datasets from nonhuman primates, including a 3D marmoset reference atlas. We elucidate molecular signature for transient gain competence fate peri-implantation epiblast development....
Rabbit embryos develop as bilaminar discs at gastrulation in humans and most other mammals, whereas rodents egg cylinders. Primordial germ cells (PGCs) appear to originate during according many systematic studies on mammalian embryos. Here, we show that rabbit PGC (rbPGC) specification occurs the posterior epiblast onset of gastrulation. Using newly derived pluripotent stem cells, robust rapid induction rbPGC-like vitro with WNT BMP morphogens, which reveals SOX17 critical regulator rbPGC...
ABSTRACT The trophoblast lineage safeguards fetal development by mediating embryo implantation, immune tolerance, nutritional supply and gas exchange. Human stem cells (hTSCs) provide a platform to study specification of placental tissues; however, the regulatory network controlling self-renewal remains elusive. Here, we present single-cell atlas human from zygote mid-gestation together with profiling hTSCs. We determine transcriptional networks lineages in vivo leverage probabilistic...
Epigenetic resetting in the mammalian germ line entails acute DNA demethylation, which lays foundation for gametogenesis, totipotency, and embryonic development. We characterize epigenome of hypomethylated human primordial cells (hPGCs) to reveal mechanisms preventing widespread derepression genes transposable elements (TEs). Along with loss methylation, we show that hPGCs exhibit a profound reduction repressive histone modifications resulting diminished heterochromatic signatures at most...
Mammalian embryogenesis relies on glycolysis and oxidative phosphorylation to balance the generation of biomass with energy production. However, dynamics metabolic regulation in postimplantation embryo vivo have remained elusive due inaccessibility implanted conceptus for biochemical studies. To address this issue, we compiled single-cell profiling data six mammalian species determined their through associated gene expression. Strikingly, identify a conserved switch from bivalent respiration...
Fates of differentiated cells in our body can be induced to change by nuclear reprogramming. In this way, valuable for therapeutic purposes and disease modeling produced. However, the efficiency process is low, partly due properties somatic donor nuclei which stabilize their fate but also act as barriers reprogramming-associated cell changes. The identity these reprogramming not fully understood. Here, we developed an artificial intelligence-based approach model used it identify chromatin...
Abstract Motivation: The generation of time series transcriptomic datasets collected under multiple experimental conditions has proven to be a powerful approach for disentangling complex biological processes, allowing the reverse engineering gene regulatory networks (GRNs). Most methods GRNs from assume that each were generated with identical topology. In this study, we outline hierarchical, non-parametric Bayesian using can applied in number novel situations including: (i) where different,...
Leaf senescence involves degenerative but active biological processes that require balanced regulation of pro- and anti-senescing activities. Ethylene cytokinin are major antagonistic regulatory hormones control the timing progression rate leaf senescence. To identify roles these in Arabidopsis, global gene expression profiles detached leaves wild type, an ethylene-insensitive mutant (ein2/ore3), a constitutive response (ahk3/ore12) were investigated during dark-induced Comparative...
SUMMARY The photosynthetic capacity of mature leaves increases after several days’ exposure to constant or intermittent episodes high light (HL) and is manifested primarily as changes in chloroplast physiology. How this chloroplast‐level acclimation HL initiated controlled unknown. From expanded Arabidopsis leaves, we determined HL‐dependent transcript abundance 3844 genes a 0–6 h time‐series transcriptomics experiment. It was hypothesized that among such were those contribute the initiation...
Here we introduce the causal structure identification (CSI) package, a Gaussian process based approach to inferring gene regulatory networks (GRNs) from multiple time series data. The standard CSI infers single GRN via joint learning datasets; hierarchical (HCSI) separate for each dataset, albeit with constrained favor similar structures, allowing of context specific networks. software is implemented in MATLAB and includes graphical user interface (GUI) friendly inference. Finally GUI can be...
Abstract Motivation: Time course data are often used to study the changes a biological process after perturbation. Statistical methods have been developed determine whether such perturbation induces over time, e.g. comparing perturbed and unperturbed time dataset uncover differences. However, existing do not provide principled statistical approach identify specific when two datasets first begin diverge perturbation; we call this time. Estimation of for different variables in allows us...
Abstract The sperm epigenome is thought to affect the developmental programming of resulting embryo, influencing health and disease in later life. Age‐related methylation changes old fathers may mediate increased risks for reproductive offspring medical problems. impact paternal age on has been extensively studied humans and, a lesser extent, rodents cattle. Here, we performed comparative analysis effects protein‐coding genes human marmoset methylomes. gained growing importance as non‐human...
Meiosis is the cell division that halves genetic component of diploid cells to form gametes or spores. To achieve this, meiotic undergo a radical spatial reorganisation chromosomes. This prerequisite for pairing parental homologous chromosomes and reductional division, which number in daughter cells. Of particular note change from centromere clustered layout (Rabl configuration) telomere conformation (bouquet stage). The contribution bouquet structure chromosome uncertain. We have developed...