A5066250791- Pluripotent Stem Cells Research
- Epigenetics and DNA Methylation
- CRISPR and Genetic Engineering
- Renal and related cancers
- Animal Genetics and Reproduction
- Genetic Syndromes and Imprinting
- Birth, Development, and Health
- Cancer-related gene regulation
- Genetics and Neurodevelopmental Disorders
- DNA and Nucleic Acid Chemistry
- Pancreatic function and diabetes
- Peroxisome Proliferator-Activated Receptors
- Histone Deacetylase Inhibitors Research
- Genetic and Clinical Aspects of Sex Determination and Chromosomal Abnormalities
- 3D Printing in Biomedical Research
- Adipokines, Inflammation, and Metabolic Diseases
- RNA Research and Splicing
- Congenital heart defects research
- Prenatal Screening and Diagnostics
- Adipose Tissue and Metabolism
- Ethics and Legal Issues in Pediatric Healthcare
- Biomedical Ethics and Regulation
- Neurogenesis and neuroplasticity mechanisms
- Genetics, Aging, and Longevity in Model Organisms
- Genomic variations and chromosomal abnormalities
Plexxikon (United States)
2008-2021
University of North Carolina Wilmington
2021
The Francis Crick Institute
2009-2020
Whitehead Institute for Biomedical Research
2011-2015
Massachusetts Institute of Technology
2012
Embryonic stem cells (ESCs) of mice and humans have distinct molecular biological characteristics, raising the question whether an earlier, "naive" state pluripotency may exist in humans. Here we took a systematic approach to identify small molecules that support self-renewal naive human ESCs based on maintenance endogenous OCT4 distal enhancer activity, signature ground pluripotency. Iterative chemical screening identified combination five kinase inhibitors induces maintains activity when...
Highlights•Combined loss of all three Tet enzymes restricts normal differentiation ESCs•Tet null ESCs contribute poorly to developing embryos and cannot support development•Tet causes promoter hypermethylation deregulation developmental genesSummaryTet (Tet1/2/3) convert 5-methylcytosine (5mC) 5-hydroxymethylcytosine (5hmC) are dynamically expressed during development. Whereas individual or combined deficiency Tet1/2 allows for embryogenesis, the effect complete activity 5hmC marks in...
(Cell Stem Cell 15, 471–487; October 2, 2014) We have identified two errors in the data presentation version of this paper originally published online on July 24, 2014. Neither them affects results or conclusions presented any significant way. The issues are as follows: Figure 3. chemical structure shown 3C did not represent WH-4-023, but instead a closely related LCK/SRC inhibitor called WH-4-025. To correct figure we replaced with for WH-4-023 and, completeness, added citation to legend...
In a search for more effective anti-diabetic treatment, we used process coupling low-affinity biochemical screening with high-throughput co-crystallography in the design of series compounds that selectively modulate activities all three peroxisome proliferator-activated receptors (PPARs), PPARalpha, PPARgamma, and PPARdelta. Transcriptional transactivation assays were to select from this chemical bias toward partial agonism circumvent clinically observed side effects full PPARgamma agonists....
Trisomic animals lose third chromosome Generally, when a sex is added to the normal two in mammals (XX for female and XY male), developmental defects result. Mice that are trisomic chromosomes infertile. Hirota et al. demonstrate reprogramming cells from sterile mice with trisomies XXY or XYY generates stem cells. Sperm generated these could give rise healthy, fertile offspring. Reprogramming also promoted loss of extra patients Klinefelter (XXY) Down (trisomy 21) syndrome. Science , this...
Sex chromosomes shape male (XY) - female (XX) differences in development and disease. These can be modelled vitro by comparing XY XX human induced pluripotent stem cells (hiPSCs). However, this system, inter-individual autosomal variation unstable X-dosage compensation confound identification of sex chromosomal effects. Here, we utilise chromosome loss XXY fibroblasts to generate hiPSCs that are autosomally isogenic exhibit stable compensation. We also create X-monosomic (XO) hiPSCs,...
Acute myeloid leukemia patients with FLT3-ITD mutations have a high risk of relapse and death. FLT3 tyrosine kinase inhibitors improve overall survival, but their efficacy is limited most who will ultimately die the disease. Even potent inhibition, disease persists within bone marrow microenvironment, mainly due to stroma activating parallel signaling pathways that maintain pro-survival factors. BET suppress factors such as MYC BCL2, these drugs thus far shown only single-agent clinical...
Hand genes are required for the development of vertebrate jaw, heart, peripheral nervous system, limb, gut, placenta, and decidua. Two paralogues, Hand1 Hand2, present in most vertebrates, where they mediate different functions yet overlap expression. In ray-finned fishes, gene expression function is only known zebrafish, which represents rare condition having a single gene, hand2. Here we describe developmental hand1 hand2 cichlid Copadichromis azureus.