A5002246823- Pluripotent Stem Cells Research
- Single-cell and spatial transcriptomics
- Gene Regulatory Network Analysis
- Renal and related cancers
- Reproductive Biology and Fertility
- Gene expression and cancer classification
- MicroRNA in disease regulation
- Fungal and yeast genetics research
- interferon and immune responses
- Prenatal Screening and Diagnostics
- Chromosomal and Genetic Variations
- Cell Image Analysis Techniques
- Genomics and Chromatin Dynamics
- Epigenetics and DNA Methylation
- CRISPR and Genetic Engineering
- Reproductive System and Pregnancy
- Neurogenesis and neuroplasticity mechanisms
- Circular RNAs in diseases
- RNA Research and Splicing
University of Exeter
2022-2025
The Francis Crick Institute
2023-2025
Wellcome/MRC Cambridge Stem Cell Institute
2022-2023
University of Cambridge
2022-2023
Johns Hopkins University
2017-2018
Johns Hopkins Medicine
2017
The hypoblast is an essential extraembryonic tissue set aside within the inner cell mass in blastocyst. Research with human embryos challenging. Thus, stem models that reproduce differentiation provide valuable alternatives. We show here naive pluripotent (PSC) to proceeds via reversion a transitional ICM-like state from which emerges concordance trajectory blastocysts. identified window when fibroblast growth factor (FGF) signaling critical for specification. Revisiting FGF revealed...
A major challenge in single-cell gene expression analysis is to discern meaningful cellular heterogeneity from technical or biological noise. To address this challenge, we present entropy sorting (ES), a mathematical framework that distinguishes genes indicative of cell identity. ES achieves an unsupervised manner by quantifying if observed correlations between features are more likely have occurred due random chance versus dependent relationship, without the need for any user-defined...
Tissue development relies on the coordinated differentiation of stem cells in dynamically changing environments. The formation vertebrate neural tube from caudal lateral epiblast (CLE) is a well characterized example. Despite an understanding signalling pathways involved, gene regulatory mechanisms remain poorly defined. To address this, we developed multiplexed vivo CRISPR screening approach chick embryos targeting genes expressed and tube. This revealed role for MLLT3, component super...
ABSTRACT Successful human pregnancy depends upon rapid establishment of three founder lineages: the trophectoderm, epiblast and hypoblast, which together form blastocyst. Each plays an essential role in preparing embryo for implantation subsequent development. Several models have been proposed to define lineage segregation. One suggests that all lineages specify simultaneously; another favours differentiation trophectoderm before separation either via hypoblast from established epiblast, or...
We designed and synthesized synI, which is ∼21.6% shorter than native chrI, the smallest chromosome in Saccharomyces cerevisiae. SynI was for attachment to another synthetic due concerns surrounding potential instability karyotype imbalance now attached synIII, yielding first yeast fusion chromosome. Additional chromosomes were constructed study nuclear function. ChrIII-I chrIX-III-I have twisted structures, depend on silencing protein Sir3. As a smaller chromosome, chrI also faces special...
Naive pluripotent stem cells (PSCs) are counterparts of early epiblast in the mammalian embryo. Mouse and human naive PSCs differ self-renewal requirements extraembryonic lineage potency. Here, we investigated generation chimpanzee PSCs. Colonies generated by resetting or reprogramming failed to propagate. We discovered that is enabled inhibition Polycomb repressive complex 2 (PRC2). Expanded show global transcriptome proximity embryo pre-implantation epiblast, with shared expression a...
Analysis of single cell transcriptomics (scRNA-seq) data is typically performed after subsetting to highly variable genes (HVGs). Here, we show that Entropy Sorting provides an alternative mathematical framework for feature selection. On synthetic datasets, continuous Sort Feature Weighting (cESFW) outperforms HVG selection in distinguishing cell-state-specific genes. We apply cESFW six merged scRNA-seq datasets spanning human early embryo development. Without smoothing or augmenting the raw...
Abstract Successful human pregnancy depends upon rapid establishment of three founder lineages: trophectoderm, epiblast and hypoblast, which together form the blastocyst. Each plays an essential role in preparing embryo for implantation subsequent development. Several models are proposed to define lineage segregation. The first suggests that all specify simultaneously; second favours differentiation trophectoderm before separation either via hypoblast from established epiblast, or production...
SUMMARY As part of the Synthetic Yeast 2.0 (Sc2.0) project, we designed and synthesized synthetic chromosome I. The total length synI is ∼21.4% shorter than wild-type I, smallest in Saccharomyces cerevisiae . SynI was for attachment to another due concerns potential instability karyotype imbalance. We used a variation previously developed, robust CRISPR-Cas9 method fuse I other arms varying length: chrIXR (84kb), chrIIIR (202kb) chrIVR (1Mb). All fusion strains grew like so decided attach...
ABSTRACT Single cell transcriptomics (scRNA-seq) transforms our capacity to define states and reveal developmental trajectories. Resolution is challenged, however, by high dimensionality noisy data. Analysis therefore typically performed after sub-setting highly variable genes (HVGs). However, existing HVG selection techniques have been found poor agreement with one another, tend be biased towards expressed genes. Entropy sorting provides an alternative mathematical framework for feature...
SUMMARY The hypoblast is an essential extra-embryonic tissue set aside within the inner cell mass early in mammalian embryo development, blastocyst. Research with human embryos challenging. Thus, stem models that reproduce differentiation provide valuable alternatives. We show here naïve PSC to proceeds via reversion a transitional ICM-like state, from which emerges concordance trajectory blastocysts. identified window when fibroblast growth factor (FGF) signalling critical for...
ABSTRACT A major challenge in single cell gene expression analysis is to discern meaningful cellular heterogeneity from technical or biological noise. To address this challenge, we present Entropy Sorting, a mathematical framework that distinguishes genes indicative of identity. ES achieves an unsupervised manner by quantifying if observed correlations between features are more likely have occurred due random chance versus dependent relationship, without the need for any user defined...
ABSTRACT Tissue development relies on the coordinated differentiation of stem cells in dynamically changing environments. The formation vertebrate neural tube from caudal lateral epiblast (CLE) is a well characterized example. Despite an understanding signalling pathways involved, gene regulatory mechanisms remain poorly defined. To address this, we developed multiplexed vivo CRISPR screening approach chick embryos targeting genes expressed and tube. This revealed role for MLLT3 , component...
Primordial follicles are quiescent ovarian structures comprised of a single oocyte surrounded by layer somatic supporting pregranulosa cells. follicle activation is the first step towards maturation and, ultimately, ovulation. As there finite number within ovary, their rate critical parameter female reproductive lifespan. Follicle characterised morphological and molecular changes in both cells oocytes. However, signal initiating activation, even cell-type responding to this signal, remain...