A5028138093- Pluripotent Stem Cells Research
- CRISPR and Genetic Engineering
- Genomics and Chromatin Dynamics
- Epigenetics and DNA Methylation
- Developmental Biology and Gene Regulation
- Zebrafish Biomedical Research Applications
- Renal and related cancers
- Childhood Cancer Survivors' Quality of Life
- Peroxisome Proliferator-Activated Receptors
- Drug Transport and Resistance Mechanisms
- Gene expression and cancer classification
- Neonatal Respiratory Health Research
- Palliative Care and End-of-Life Issues
- Health Sciences Research and Education
- Pregnancy and preeclampsia studies
- Mycobacterium research and diagnosis
- Herpesvirus Infections and Treatments
- Leprosy Research and Treatment
- Chronic Myeloid Leukemia Treatments
- Pharmacogenetics and Drug Metabolism
- 3D Printing in Biomedical Research
- Hip and Femur Fractures
- Congenital heart defects research
- Acute Myeloid Leukemia Research
- Genetics, Bioinformatics, and Biomedical Research
MRC Centre for Regenerative Medicine
2011-2023
University of Edinburgh
2010-2023
Edinburgh Cancer Research
2018
Medical Research Council
2008-2017
Witten/Herdecke University
2014
Salford Royal NHS Foundation Trust
2009
Juvenile Diabetes Research Foundation
2008
The Honourable Society of Lincoln's Inn
2005-2007
Cancer Research UK
2003-2006
University of Nottingham
1996-2004
Embryonic stem cell (ESC) self-renewal efficiency is determined by the level of Nanog expression. However, mechanisms which functions remain unclear, and in particular, direct target genes are uncharacterized. Here we investigate ESCs expressing different levels Nanog−/− cells with distinct functionally inducible proteins to identify Nanog-responsive genes. Surprisingly, these constitute a minor fraction that binds. Prominent among Nanog-reponsive Estrogen-related receptor b (Esrrb). binds...
Embryonic stem cell (ESC) pluripotency is governed by a gene regulatory network centered on the transcription factors Oct4 and Nanog. To date, robust self-renewing ESC states have only been obtained through chemical inhibition of signaling pathways or enforced transgene expression. Here, we show that ESCs with reduced expression resulting from heterozygosity also exhibit stabilized pluripotent state. Despite having expression, Oct4+/− increased genome-wide binding Oct4, particularly at...
The thymus is the central site of T-cell development and thus fundamental importance to immune system, but little information exists regarding molecular regulation in humans. Here we demonstrate, via spatial temporal expression analyses, that genetic mechanisms known regulate mouse organogenesis are conserved In addition, provide evidence human thymic epithelium derives solely from third pharyngeal pouch, as mouse, contrast previous suggestions. Finally, define timing onset hematopoietic...
The elongating mouse anteroposterior axis is supplied by progenitors with distinct tissue fates. It not known whether these confer pattern to the embryo. We have analysed progenitor population transcriptomes in primitive streak and tail bud throughout axial elongation. Transcriptomic signatures distinguish three types (neuromesodermal, lateral/paraxial mesoderm notochord progenitors; NMPs, LPMPs NotoPs). Both NMP LPMP change extensively over time. In particular, NMPs upregulate Wnt, Fgf,...
Point mutations within the histone H3.3 are frequent in aggressive childhood brain tumors known as pediatric high-grade gliomas (pHGGs). Intriguingly, distinct arise discrete anatomical regions: H3.3-G34R forebrain and H3.3-K27M preferentially hindbrain. The reasons for this contrasting etiology unknown. By engineering human fetal neural stem cell cultures from regions, we demonstrate here that cell-intrinsic regional identity provides differential responsiveness to each mutant mirrors...
Abstract Gene expression profiles were determined from presentation peripheral blood and bone marrow samples of 28 patients with acute myeloid leukemia (AML). Hierarchical clustering sorted the into separate groups, each representing one major cytogenetic classes in AML [i.e., t(8;21), t(15;17), inv(16), 11q23, normal karyotype]. Statistical group comparison identified genes whose was strongly correlated these chromosomal classes. Moreover, karyotype AMLs characterized by distinctive...
Abstract The functional relationships and properties of different subtypes dendritic cells (DC) remain largely undefined. To better characterize these cells, we used global gene analysis to determine expression patterns among murine CD11chigh DC subsets. CD4+, CD8α+, CD8α− CD4− (double negative (DN)) were purified from spleens normal C57/BL6 mice analyzed using Affymetrix microarrays. CD4+ CD8α+ subsets showed distinct basal profiles differing by >200 individual genes. These included...
Abstract Purpose: At presentation, most cases of adenocarcinoma the esophagus (ACE) are inoperable. Although chemotherapy can prolong survival, patients eventually die as a result refractory disease. Epidermal growth factor receptor (EGFR) is almost universally expressed in ACE and negative prognostic factor. Experimental Design: This open-label, two-center, noncomparative, two-part phase II trial assessed EGFR tyrosine kinase inhibitor gefitinib (500 mg/d) with advanced, inoperable ACE. The...
In the developing embryo, hematopoietic stem cells (HSCs) emerge from aorta-gonad-mesonephros (AGM) region, but molecular regulation of this process is poorly understood. Recently, progression E9.5 to E10.5 and polarity along dorso-ventral axis have been identified as clear demarcations supportive HSC niche. To identify novel secreted regulators maturation, we performed RNA sequencing over these spatiotemporal transitions in AGM region OP9 cell line. Screening several proteins through an ex...
The thymus is essential for a functional immune system, because the thymic stroma uniquely supports T lymphocyte development. We have previously identified epithelial progenitor population from which arises and demonstrated its ability to generate an organized upon transplantation. These cells (TEPC) are defined by surface determinants recognized mAbs MTS20 MTS24, were also recently shown identify keratinocyte in skin. However, biochemical nature of MTS24 has remained unknown. Here we show,...
Article11 August 2015Open Access Source Data Selective influence of Sox2 on POU transcription factor binding in embryonic and neural stem cells Tapan Kumar Mistri Department Chemistry, National University Singapore, Singapore Developmental Cellomics Laboratory, Genome Institute MRC Centre for Regenerative Medicine, Stem Cell Research, School Biological Sciences, Edinburgh, UK Search more papers by this author Arun George Devasia Lee Thean Chu Wei Ping Ng Florian Halbritter Douglas Colby Ben...
CRISPR/Cas9 can be used for precise genetic knock-in of epitope tags into endogenous genes, simplifying experimental analysis protein function. However, Cas9-assisted tagging in primary mammalian cell cultures is often inefficient and reliant on plasmid-based selection strategies. Here, we demonstrate improved efficiencies diverse (V5, 3XFLAG, Myc, HA) using co-delivery Cas9 pre-complexed with two-part synthetic modified RNAs (annealed crRNA:tracrRNA) single-stranded oligodeoxynucleotide...
The identification of transcription factor (TF) binding sites in the genome is critical to understanding gene regulatory networks (GRNs). While ChIP-seq commonly used identify TF targets, it requires specific ChIP-grade antibodies and high cell numbers, often limiting its applicability. D NA a denine m ethyltransferase id entification (DamID), developed widely Drosophila , distinct technology investigate protein–DNA interactions. Unlike ChIP-seq, does not require antibodies, precipitation...
Genomic clones for Cyp4a12 and a novel member of the murine Cyp4a gene family were isolated. The gene, designated Cyp4a14, has GC rich sequence immediately 5′ transcription start site, is similar to rat CYP4A2 CYP4A3 genes. Cyp4a14 spans approximately 13 kb, contains 12 exons; similarity falls off 300 bp upstream from site. In view known sex-specific expression inducibility was examined. highly inducible in liver when mice treated with peroxisome proliferator, methylclofenapate; induction...
Recently, we showed a natural reprogramming process during infection with Mycobacterium leprae (ML), the causative organism of human leprosy. ML hijacks notable plasticity adult Schwann cells in peripheral nervous system (PNS), bacteria's preferred nonimmune niche, to reprogram infected progenitor/stem cell-like (pSLCs). Whereas appear use this as sophisticated bacterial strategy spread other tissues, understanding mechanisms may shed new insights into basic biology cellular and development...
Abstract Induced pluripotent stem cell (iPSC) reprogramming is inefficient and understanding the molecular mechanisms underlying this inefficiency holds key to successfully control cellular identity. Here, we report 24 roadblock genes identified by CRISPR/Cas9-mediated genome-wide knockout (KO) screening. Of these, depletion of predicted KRAB zinc finger protein (KRAB-ZFP) Zfp266 strongly consistently enhances murine iPSC generation in several settings, emerging as most robust roadblock. We...
The Raf protein kinases are major effectors of Ras GTPases and key components the transcriptional response to serum factors, acting at least in part through extracellular signal-regulated kinase/mitogen-activated kinase pathway. It has recently been suggested that also may trigger other as yet uncharacterized signaling pathways. Here, we have used cDNA microarrays dissect changes gene expression induced by activation inducible c-Raf-1 constructs human mammary epithelial ovarian cells....