A5030769349- RNA Research and Splicing
- Pluripotent Stem Cells Research
- CRISPR and Genetic Engineering
- Amyotrophic Lateral Sclerosis Research
- Genetics, Aging, and Longevity in Model Organisms
- Neurogenetic and Muscular Disorders Research
- RNA and protein synthesis mechanisms
- Genetic Syndromes and Imprinting
- Epigenetics and DNA Methylation
- Prenatal Screening and Diagnostics
- Single-cell and spatial transcriptomics
- Renal and related cancers
- RNA modifications and cancer
- Biotin and Related Studies
- Plant biochemistry and biosynthesis
- Gene Regulatory Network Analysis
- Photosynthetic Processes and Mechanisms
Vienna Biocenter
2020-2024
University of Vienna
2020-2024
Max Perutz Labs
2020-2024
Medical University of Vienna
2022-2024
Memorial Sloan Kettering Cancer Center
2024
Sapienza University of Rome
2017-2019
National Academies of Sciences, Engineering, and Medicine
2000
The FUS gene has been linked to amyotrophic lateral sclerosis (ALS). is a ubiquitous RNA-binding protein, and the mechanisms leading selective motoneuron loss downstream of ALS-linked mutations are largely unknown. We report transcriptome analysis human purified motoneurons, obtained from wild-type or mutant isogenic induced pluripotent stem cells (iPSCs). Gene ontology differentially expressed genes identified significant enrichment pathways previously associated sporadic ALS other...
Resource9 March 2021Open Access Transparent process Cooperative genetic networks drive embryonic stem cell transition from naïve to formative pluripotency Andreas Lackner orcid.org/0000-0003-1168-7947 Max Perutz Laboratories Vienna, University of Vienna Biocenter, AustriaThese authors contributed equally this work as first authors. Search for more papers by author Robert Sehlke Cologne Excellence Cluster Cellular Stress Response in Aging-Associated Diseases (CECAD), Cologne, GermanyThese...
In mammalian genomes, differentially methylated regions (DMRs) and histone marks including trimethylation of 3 lysine 27 (H3K27me3) at imprinted genes are asymmetrically inherited to control parentally-biased gene expression. However, neither parent-of-origin-specific transcription nor imprints have been comprehensively mapped the blastocyst stage preimplantation development. Here, we address this by integrating transcriptomic epigenomic approaches in mouse embryos. We find that seventy-one...
Cell fate transitions depend on balanced rewiring of transcription and translation programs to mediate ordered developmental progression. Components the nonsense-mediated mRNA decay (NMD) pathway have been implicated in regulating embryonic stem cell (ESC) differentiation, but exact mechanism is unclear. Here we show that NMD controls expression levels initiation factor Eif4a2 its premature termination codon-encoding isoform (Eif4a2PTC ). deficiency leads truncated eIF4A2PTC protein. elicits...
Naive pluripotency is sustained by a self-reinforcing gene regulatory network (GRN) comprising core and naive pluripotency-specific transcription factors (TFs). Upon exiting pluripotency, ES cells transition through formative post-implantation-like pluripotent state, where they acquire competence for lineage-choice. However, the mechanisms underlying disengagement from GRN initiation of are unclear. Here, we demonstrate that phosphorylated AKT acts as gatekeeper prevents nuclear localization...
The directed differentiation of pluripotent stem cells (PSCs) from panels genetically diverse individuals is emerging as a powerful experimental system for characterizing the impact natural genetic variation on developing cell types and tissues. Here, we establish new PSC lines approaches modeling embryonic development in diverse, outbred mouse stock (Diversity Outbred mice). We show that range inbred can be stably maintained primed state (epiblast -- EpiSCs) contribution to phenotypic...
Abstract In the mammalian embryo, epiblast cells must exit their naïve state and acquire formative pluripotency. This cell transition is recapitulated by mouse embryonic stem (ESCs), which undergo pluripotency progression in defined conditions vitro . However, our understanding of molecular cascades gene-networks involved from remains fragmented. Here we employed a combination genetic screens haploid ESCs, CRISPR/Cas9 gene disruption, large-scale transcriptomics computational systems-biology...
The motor neuron disease Amyotrophic Lateral Sclerosis (ALS) has been genetically linked to mutations in RNA binding proteins (RBPs), including FUS. Here we report the interactome of wild-type and mutant FUS human induced Pluripotent Stem Cells (iPSC)-derived neurons (MNs). We show that, whereas protein preferentially binds introns, ALS mutation causes a shift towards 3’ untranslated regions (3’UTRs). neural specific ELAV-like RBPs are among targets. As result, ELAVL4 levels increased MNs....
ABSTRACT In mammals, chromatin marks at imprinted genes are asymmetrically inherited to control parentally-biased gene expression. This is thought predominantly involve parent-specific differentially methylated regions (DMR) in genomic DNA. However, neither parent-of-origin-specific transcription nor DMRs have been comprehensively mapped. We here address this by integrating transcriptomic and epigenomic approaches mouse preimplantation embryos (blastocysts). Transcriptome-analysis identified...
ABSTRACT Cell fate transitions depend on balanced rewiring of transcription and translation programmes to mediate ordered developmental progression. Components the nonsense-mediated mRNA decay (NMD) pathway have been implicated in regulating embryonic stem cell (ESC) differentiation, but exact mechanism is unclear. Here we show that NMD controls initiation factor Eif4a2 its premature termination codon encoding isoform ( PTC ). deficiency leads a specific truncated protein, which elicits...