A5090734944- Genetic and Clinical Aspects of Sex Determination and Chromosomal Abnormalities
- CRISPR and Genetic Engineering
- Epigenetics and DNA Methylation
- Genomics and Chromatin Dynamics
- Animal Genetics and Reproduction
- Pluripotent Stem Cells Research
- Genetics and Neurodevelopmental Disorders
- Renal and related cancers
- Cancer-related molecular mechanisms research
- Chromosomal and Genetic Variations
- RNA modifications and cancer
- Cancer Genomics and Diagnostics
- Prenatal Screening and Diagnostics
- Gene expression and cancer classification
- RNA Research and Splicing
- Renal cell carcinoma treatment
- Hemoglobinopathies and Related Disorders
- Molecular Biology Techniques and Applications
- Reproductive Biology and Fertility
- Genetic Syndromes and Imprinting
- Birth, Development, and Health
- Erythrocyte Function and Pathophysiology
- Neonatal Respiratory Health Research
- Cancer-related gene regulation
- Immune Cell Function and Interaction
Erasmus University Rotterdam
2015-2025
Erasmus MC
2016-2025
Rotterdam University of Applied Sciences
2019-2025
Oncode Institute
2018-2024
University of Patras
2024
Hellenic Open University
2024
Incyte (United States)
2024
Novartis (Switzerland)
2024
Janssen (Belgium)
2024
Erasmus MC Cancer Institute
2012-2022
Three-dimensional topology of DNA in the cell nucleus provides a level transcription regulation beyond sequence linear DNA. To study relationship between transcriptional activity and spatial environment gene, we used allele-specific chromosome conformation capture-on-chip (4C) technology to produce high-resolution maps active inactive X chromosomes female cells. We found that loci on form multiple long-range interactions, with segregation chromatin. On X, silenced lack preferred suggesting...
Progress in elucidating the molecular and cellular pathophysiology of neuropsychiatric disorders has been hindered by limited availability living human brain tissue. The emergence induced pluripotent stem cells (iPSCs) offered a unique alternative strategy using patient-derived functional neuronal networks. However, methods for reliably generating iPSC-derived neurons with mature electrophysiological characteristics have difficult to develop. Here, we report simplified differentiation...
Biallelic expression of Igf2 is frequently seen in cancers because functions as a survival factor. In many tumors the activation has been correlated with de novo methylation imprinted region. We have compared intrinsic susceptibilities region and H19, other genes, bulk genomic DNA, repetitive retroviral sequences to Dnmt1 overexpression. At low methyltransferase levels elements were methylated silenced. The nonmethylated H19 was resistant at but became fully when overexpressed from bacterial...
We have investigated the role of erythroid Kruppel-like factor (EKLF) in expression human beta-globin genes compound EKLF knockout/human beta-locus transgenic mice. affects only adult mouse homozygous knockout mice; heterozygous mice are unaffected. Here we show that express epsilon and gamma-globin normally embryonic red cells. However, fetal liver erythropoiesis, which is marked by a period gamma- beta-gene competition alternately transcribed, exhibits an altered ratio to transcription....
During red blood cell development, differentiation and cycle progression are intimately uniquely linked through interdependent mechanisms involving the erythroid transcriptional suppressor PU.1 cyclin-dependent kinase inhibitor p57KIP2.
In somatic cells of female placental mammals, one the two X chromosomes is transcriptionally silenced to accomplish an equal dose X-encoded gene products in males and females. Initiation random chromosome inactivation (XCI) thought be regulated by activators autosomally encoded suppressors controlling Xist. Spreading Xist RNA leads silencing cis. Here, we demonstrate that dependent XCI activator RNF12/RLIM acts trans activates We did not find evidence for RNF12-mediated regulation through...
During early embryonic development, one of the two X chromosomes in mammalian female cells is inactivated to compensate for a potential imbalance transcript levels with male cells, which contain single chromosome. Here, we use mouse stem (ESCs) non-random chromosome inactivation (XCI) and polymorphic study dynamics gene silencing over inactive by high-resolution allele-specific RNA-seq. Induction XCI differentiation ESCs shows that genes proximal X-inactivation center are silenced earlier...
Engineering brain organoids from human induced pluripotent stem cells (hiPSCs) is a powerful tool for modeling development and neurological disorders. Rett syndrome (RTT), rare neurodevelopmental disorder, can greatly benefit this technology, since it affects multiple neuronal subtypes in forebrain sub-regions. We have established dorsal ventral control RTT patient-specific hiPSCs recapitulating 3D organization functional network complexity. Our data revealed premature of the deep-cortical...
XIST (X-inactive specific transcript) long noncoding RNA (lncRNA) is responsible for X chromosome inactivation (XCI) in placental mammals, yet it accumulates on both chromosomes human female preimplantation embryos without triggering silencing. The XACT (X-active coating lncRNA coaccumulates with active and may antagonize function. Here, we used embryonic stem cells a naive state of pluripotency to assess the function shaping chromatin transcriptional landscapes during development. We show...
We have characterized mRNA expression and transcription of the mouse α - β-globin loci during development. S1 nuclease primary transcript in situ hybridization analyses demonstrate that all seven murine globin genes ( ζ , α1 α2 εy βH1 βmaj βmin ) are transcribed primitive erythropoiesis, however is restricted to erythroid lineage. Transcription cells EKLF-dependent demonstrating EKLF activity embryonic red cells. Novel kinetic suggest multigene β locus occurs via alternating single-gene...
DNA replication occurs in a defined temporal order known as the replication-timing (RT) program. RT is regulated during development discrete chromosomal units, coordinated with transcriptional activity and 3D genome organization. Here, we derived distinct cell types from F1 hybrid musculus × castaneus mouse crosses exploited high single-nucleotide polymorphism (SNP) density to characterize allelic differences (Repli-seq), organization (Hi-C promoter-capture Hi-C), gene expression (total...