A5087616533- CRISPR and Genetic Engineering
- Epigenetics and DNA Methylation
- Pluripotent Stem Cells Research
- Animal Genetics and Reproduction
- Cancer-related gene regulation
- Genomics and Chromatin Dynamics
- RNA Research and Splicing
- Acute Myeloid Leukemia Research
- RNA Interference and Gene Delivery
- Renal and related cancers
- RNA modifications and cancer
- Hematopoietic Stem Cell Transplantation
- Congenital heart defects research
- Protein Degradation and Inhibitors
- Genetic and Clinical Aspects of Sex Determination and Chromosomal Abnormalities
- Cancer Cells and Metastasis
- Viral Infectious Diseases and Gene Expression in Insects
- RNA and protein synthesis mechanisms
- DNA Repair Mechanisms
- T-cell and B-cell Immunology
- Developmental Biology and Gene Regulation
- Diabetes and associated disorders
- 3D Printing in Biomedical Research
- Gene Regulatory Network Analysis
- Pancreatic function and diabetes
TU Dresden
2015-2025
Center for Systems Biology Dresden
2018-2022
Berlin-Brandenburger Centrum für Regenerative Therapien
2010-2013
MRC Centre for Regenerative Medicine
2012
University of Edinburgh
2012
Max Planck Society
2009-2011
Massachusetts Institute of Technology
2010
Leiden University Medical Center
2007
Heidelberg University
2007
University Hospital Heidelberg
2007
In 2007, the International Knockout Mouse Consortium (IKMC) made ambitious promise to generate mutations in virtually every protein-coding gene of mouse genome a concerted worldwide action. Now, 5 years later, IKMC members have developed high-throughput trapping and, particular, gene-targeting pipelines and generated more than 17,400 mutant murine embryonic stem (ES) cell clones 1,700 strains, most them conditional. A common web portal (www.knockoutmouse.org) has been established, allowing...
Developmental signals such as Wnts are often presented to cells in an oriented manner. To examine the consequences of local Wnt signaling, we immobilized proteins on beads and introduced them embryonic stem culture. At single-cell level, Wnt-bead induced asymmetric distribution Wnt-β-catenin signaling components, plane mitotic division, directed inheritance centrosomes. Before cytokinesis was completed, Wnt-proximal daughter cell expressed high levels nuclear β-catenin pluripotency genes,...
Tyrosine site-specific recombinases (SSRs) including Cre and FLP are essential tools for DNA genome engineering. has long been recognized as the best SSR engineering, particularly in mice. Obtaining another that is good will be a valuable addition to genomic toolbox. To this end, we have developed validated reagents Dre-rox system. These include an Escherichia coli-inducible expression vector based on temperature-sensitive pSC101 plasmid, mammalian CAGGs promoter, rox-lacZ reporter embryonic...
Trimethylation of histone H3 lysine 4 (H3K4me3) at the promoters actively transcribed genes is a universal epigenetic mark and key product Trithorax group action. Here, we show that Mll2, one six Set1/Trithorax-type H3K4 methyltransferases in mammals, required for trimethylation bivalent mouse embryonic stem cells. Mll2 bound to but also most active promoters, which do not require H3K4me3 or mRNA expression. By contrast, Set1 complex (Set1C) subunit Cxxc1 primarily promoters. This indicates...
During gametogenesis and pre-implantation development, the mammalian epigenome is reprogrammed to establish pluripotency in epiblast. Here we show that histone 3 lysine 4 (H3K4) methyltransferase, MLL2, controls most of promoter-specific chromatin modification, H3K4me3, during oogenesis early development. Using conditional knockout mutagenesis a hypomorph model, Mll2 deficiency oocytes results anovulation oocyte death, with increased transcription p53, apoptotic factors, Iap elements. MLL2...
A short G1 phase is a characteristic feature of mouse embryonic stem cells (ESCs). To determine if there causal relationship between restriction and pluripotency, we made use the Fluorescence Ubiquitination Cell Cycle Indicator (FUCCI) reporter system to FACS-sort ESCs in different cell cycle phases. Hence, appeared be more susceptible differentiation, particularly when self-renewed naïve state pluripotency. Transitions from ground naïve, then primed states pluripotency were associated with...
The plasticity of pluripotent stem cells provides new possibilities for studying development, degeneration, and regeneration. Protocols the differentiation retinal organoids from embryonic have been developed, which either recapitulate complete eyecup morphogenesis or maximize photoreceptor genesis. Here, we developed a protocol efficient generation large, 3D-stratified that does not require evagination optic-vesicle-like structures, so far limited organoid yield. Analysis gene expression in...
POU transcription factors are involved in transcriptional regulation during early embryonic development and cell differentiation. Oct-4, a member of this family, has been shown to be under strict murine development. The expression Oct-4 correlates with the undifferentiated phenotype mouse preimplantation embryo. In study, gene construct consisting selected parts region upstream from as promoter/enhancer, enhanced green fluorescent protein (EGFP) reporter five exons (GOF18-ΔPE EGFP) was...
The POU transcription factor Oct-4 is expressed specifically in the germ line, pluripotent cells of pregastrulation embryo and stem cell lines derived from early embryo. Osteopontin (OPN) a protein secreted by preimplantation contains GRGDS motif that can bind to specific integrin subtypes modulate adhesion/migration. We show OPN are coexpressed mouse during differentiation embryonal lines. Immunoprecipitation first intron (i-opn) covalently fixed chromatin Oct-4-specific antibodies...
Epigenesis is the process whereby daughters of a dividing cell retain chromatin state determined before division. The best-studied cases involve inheritance heterochromatic chromosomal domains, and little known about specific gene regulation by epigenetic mechanisms. Recent evidence shows that epigenesis pivots on methylation nucleosomes at histone 3 lysines 4, 9 or 27. Bioinformatics indicates mammals have several enzymes for each these methylations, including least six lysine 4...
Identifying molecular pathways regulating the development of pacemaking and coordinated heartbeat is crucial for a comprehensive mechanistic understanding arrhythmia-related diseases. Elucidation these has been complicated mainly by an insufficient definition developmental structures involved in processes unavailability animal models specifically targeting relevant tissues. Here, we report on highly restricted expression pattern homeodomain transcription factor Shox2 sinus venosus...
Alteration of the mouse genome through homologous recombination in embryonic stem (ES) cells is most accurate and versatile way to dissect gene function a vertebrate model. Most often, selectable marker used create knockout allele by replacing an essential part gene. However, strategies are limited because mutation present constitutively. Conditional approaches based on Cre-loxP site-specific (SSR) system address this limitation; however, it requires that all parts targeted remain ES cells....
Histone 3 lysine 4 (H3K4) methylation is a universal epigenetic mark. In mammals, there are six H3K4 methyltransferases related to yeast Set1 and fly Trithorax, including two orthologs of Set1: Setd1a Setd1b. Here we show that mouse required for gastrulation, whereas Setd1b-deficient embryos survive E11.5 but grossly retarded. knockout implant do not proceed past the epiblast. Furthermore, until inner cell mass has formed, at which stage it replaced Mll2 as major methyltransferase....
Histone methylation is thought to be central the epigenetic mechanisms that maintain and confine cellular identity in multi-cellular organisms. To examine roles homeostasis, we conditionally mutated histone 3 lysine 4 methyltransferase, Mll2, embryonic stem (ES) cells, during development adult mice using tamoxifen-induced Cre recombination.In ES expression profiling unexpectedly revealed only one gene, Magoh2, dependent upon Mll2 few other genes were affected. Loss of caused loss H3K4me3 at...
Meiotic crossover formation involves the repair of programmed DNA double-strand breaks (DSBs) and synaptonemal complex (SC) formation. Completion these processes must precede meiotic divisions in order to avoid chromosome abnormalities gametes. Enduring key questions meiosis have been how progression are coordinated, whether inappropriate asynapsis is monitored, elicits prophase arrest via mechanisms that distinct from surveillance unrepaired DSBs. We disrupted meiosis-specific mouse HORMAD2...
Abstract Recently, a codon improved version of the Flpe site specific recombinase, termed Flpo, was reported as having greatly performance in mammalian cell applications. However, degree improvement could not be estimated because essentially no activity observed. Here, we compare and Flpo accurately assay to estimate that is about five times more active than similar Cre Dre. Consequently, generated deleter mouse line from JM8 C57Bl/6 ES cells used EUCOMM KOMP systematic knock‐out programs....
Transgenesis is a cornerstone of molecular biology. The ability to integrate specifically engineered piece DNA into the genome living system fundamental our efforts understand life and exploit its implications for medicine, nanotechnology bioprospecting. However, transgenesis has been hampered by position effects multi-copy integration problems, which are mainly due use small, plasmid-based transgenes. Large transgenes based on native genomic regions cloned bacterial artificial chromosomes...
The neural crest (NC) is a multipotent embryonic cell population that generates distinct types in an axial position-dependent manner. production of NC cells from human pluripotent stem (hPSCs) valuable approach to study biology. However, the origin trunk remains undefined and current vitro differentiation strategies induce only modest yield cells. Here we show hPSC-derived progenitors, posteriorly-located drivers axis elongation, give rise their derivatives. Moreover, define molecular...