A5046289486- Pluripotent Stem Cells Research
- Epigenetics and DNA Methylation
- Reproductive Biology and Fertility
- Prenatal Screening and Diagnostics
- Renal and related cancers
- Genetic Syndromes and Imprinting
- CRISPR and Genetic Engineering
- 3D Printing in Biomedical Research
- Birth, Development, and Health
- Animal Genetics and Reproduction
- Neuroscience and Neural Engineering
- Assisted Reproductive Technology and Twin Pregnancy
- Tissue Engineering and Regenerative Medicine
- Sperm and Testicular Function
- Pregnancy and preeclampsia studies
- Reproductive Physiology in Livestock
- Additive Manufacturing and 3D Printing Technologies
- Genomic variations and chromosomal abnormalities
- Zebrafish Biomedical Research Applications
- Homelessness and Social Issues
- Fatigue and fracture mechanics
- Lipid metabolism and biosynthesis
- Engineering Structural Analysis Methods
- RNA Research and Splicing
- Congenital heart defects research
University of Nottingham
2008-2023
NHS England
2023
Nottingham University Hospitals NHS Trust
2023
Roslin Institute
1998-2019
Queen's Medical Centre
2002-2019
University of Edinburgh
2019
St. John’s Health Sciences Centre
2008
Loughborough University
2004
Scottish Agricultural Science Agency
2000
Oxford Instruments (United Kingdom)
1989
A complex combination of adult health-related disorders can originate from developmental events that occur in utero . The periconceptional period may also be programmable. We report on the effects restricting supply specific B vitamins (i.e., 12 and folate) methionine, within normal physiological ranges, diet mature female sheep. hypothesized this would lead to epigenetic modifications DNA methylation preovulatory oocyte and/or preimplantation embryo, with long-term health implications for...
Congenital long QT syndromes (LQTSs) are associated with prolonged ventricular repolarization and sudden cardiac death. Limitations to existing clinical therapeutic management strategies prompted us develop a novel human in vitro drug-evaluation system for LQTS type 2 (LQT2) that will complement the vivo models. Skin fibroblasts from patient KCNH2 G1681A mutation (encodes IKr potassium ion channel) were reprogrammed induced pluripotent stem cells (hiPSCs), which subsequently differentiated...
Cardiomyocytes from human pluripotent stem cells (hPSCs-CMs) could revolutionise biomedicine. Global burden of heart failure will soon reach USD $90bn, while unexpected cardiotoxicity underlies 28% drug withdrawals. Advances in hPSC isolation, Cas9/CRISPR genome engineering and hPSC-CM differentiation have improved patient care, progressed drugs to clinic opened a new era safety pharmacology. Nevertheless, predictive using hPSC-CMs contrasts almost total success. Since this likely relates...
Abstract Although all human ESC (hESC) lines have similar morphology, express key pluripotency markers, and can differentiate toward primitive germ layers in vitro, the lineage-specific developmental potential may vary between individual lines. In current study, four hESC were cultured same feeder-free conditions to provide a standardized platform for interline analysis. A high-throughput, forced-aggregation system involving centrifugation of defined numbers hESCs V-96 plates (V-96FA) was...
Sheep fetal development at 35 days of gestation was examined following natural mating, in vitro production (IVP) fertilized embryos, or somatic cell nuclear transfer (NT). Five crossbred (Blackface × Black Welsh) and four purebred (Black fetuses their associated placentae produced by mating were morphologically normal consistent with each other. From 10 ewes receiving 21 IVP 17 (81%) recovered, 15 these (88%) normal. The NT derived from two Welsh fibroblast lines (BLW1 6). Transfer BLW1 22...
Active demethylation of cytosine residues in the sperm genome before forming a functional zygotic nucleus is thought to be an important function oocyte cytoplasm for subsequent embryonic development mouse. Conversely, this event does not occur sheep or rabbit zygote and occurs only partially cow. The aim study was investigate effect limited methylation reprogramming normal embryo on somatic nuclei. Sheep fibroblast nuclei were demethylated after electrofusion with recipient oocytes undergo...
The effects of in vitro culture systems for sheep zygotes on subsequent fetal growth and development to day 61 125 gestation were studied. Zygotes recovered from superovulated Scottish Blackface ewes approximately 36 h after intrauterine insemination using semen a single Suffolk sire cultured 5 days (a) granulosa cell co-culture system (co-culture); (b) synthetic oviductal fluid medium without serum (SOF-); (c) supplemented with human (SOF+). Control embryos donor at 6 oestrus. Embryos...
Widespread provision of human embryonic stem cells (hESCs) for therapeutic use, drug screening and disease modelling will require cell lines sustainable over long periods in culture. Since the short-term, vitro culture mammalian embryos can result DNA methylation changes, epigenetic stability hESCs warrants investigation. Existing hESC have been derived cultured under diverse conditions, providing potential programming differential changes into epigenome that may inter-line variability above...
Large-scale manufacture of human embryonic stem cells (hESCs) is prerequisite to their widespread use in biomedical applications. However, current hESC culture strategies are labor-intensive and employ highly variable processes, presenting challenges for scaled production commercial development. Here we demonstrate that passaging the lines, HUES7, NOTT1, with trypsin feeder-free conditions, compatible complete automation on CompacT SelecT, a commercially available industrially relevant...
A scalable and cost-effective synthetic polymer substrate that supports robust expansion subsequent multilineage differentiation of human pluripotent stem cells (hPSCs) with defined commercial media is presented. This can be applied to common cultureware used off-the-shelf after long-term storage. Expansion hPSCs are performed entirely on the polymeric surface, enabling clinical potential hPSC-derived realized.
In contrast to mice, in sheep no genome-wide demethylation of the paternal genome occurs within first postfertilization cell cycle. This difference could be due either an absence a demethylase activity that is present mouse ooplasm or increased protection methylated cytosine residues sperm. Here, we use interspecies intracytoplasmic sperm injection demonstrate DNA can demethylated oocytes. Surprisingly, also limited extent Our results suggest murine process facilitated by sperm-derived...
Disregulation of imprinted genes can be associated with tumorigenesis and altered cell differentiation capacity so could provide adverse outcomes for stem applications. Although the maintenance mouse primate embryonic cells in a pluripotent state has been reported to disrupt monoallelic expression several genes, available data have suggested relatively higher imprint stability human equivalents. Identification 202 heterozygous loci allowed us examine allelic 22 lines. Half examined ( IPW ,...