A5001477091- Chromosomal and Genetic Variations
- RNA modifications and cancer
- Genetics and Neurodevelopmental Disorders
- CRISPR and Genetic Engineering
- Neurogenetic and Muscular Disorders Research
- RNA and protein synthesis mechanisms
- Epigenetics and DNA Methylation
- RNA regulation and disease
- Genomics and Phylogenetic Studies
- Genomics and Chromatin Dynamics
- Pluripotent Stem Cells Research
- RNA Research and Splicing
Lund University
2019-2024
The genetic mechanisms underlying the expansion in size and complexity of human brain remain poorly understood. Long interspersed nuclear element-1 (L1) retrotransposons are a source divergent information hominoid genomes, but their importance physiological functions contribution to evolution largely unknown. Using multiomics profiling, we here demonstrate that L1 promoters dynamically active developing adult brain. L1s generate hundreds developmentally regulated cell type-specific...
Abstract SVA (SINE (short interspersed nuclear element)–VNTR (variable number of tandem repeats)– Alu ) retrotransposons remain active in humans and contribute to individual genetic variation. Polymorphic alleles harbor gene regulatory potential can cause disease. However, how insertions are controlled functionally impact human disease is unknown. Here we dissect the epigenetic regulation influence SVAs cellular models X-linked dystonia parkinsonism (XDP), a neurodegenerative disorder caused...
The human silencing hub (HUSH) complex binds to transcripts of LINE-1 retrotransposons (L1s) and other genomic repeats, recruiting MORC2 effectors remodel chromatin. How HUSH operate alongside DNA methylation, a central epigenetic regulator repeat transcription, remains largely unknown. Here we interrogate this relationship in neural progenitor cells (hNPCs), somatic model brain development that tolerates removal methyltransferase DNMT1. Upon loss or subunit TASOR hNPCs, L1s remain silenced...
Heterochromatin is characterised by an inaccessibility to the transcriptional machinery and associated with histone mark H3K9me3. erosion a hallmark of human ageing H3K9me3 lost globally in aged mammalian cells. However, functional consequences loss heterochromatin maintenance have been challenging model. In this study, we used CRISPRi-mediated deletion methyltransferase SETDB1 neural progenitor cells model disruption maintenance. Deletion had limited effect on cell viability, despite global...
Human embryonic stem cells (hESCs) and induced pluripotent (iPSCs) can be differentiated into many different cell types of the central nervous system. One challenge when using is to develop robust efficient differentiation protocols that result in homogenous cultures desired type. Here, we have utilized SMAD-inhibitors SB431542 Noggin a fully defined monolayer culture model differentiate human forebrain neural progenitors. Temporal fate analysis revealed this protocol results...
Abstract The genetic mechanisms underlying the expansion in size and complexity of human brain remains poorly understood. L1 retrotransposons are a source divergent information hominoid genomes, but their importance physiological functions contribution to evolution is largely unknown. Using multi-omic profiling we here demonstrate that L1-promoters dynamically active developing adult brain. L1s generate hundreds developmentally regulated cell-type specific transcripts, many which co-opted as...
ABSTRACT The human silencing hub (HUSH) complex binds to transcripts of LINE-1 retrotransposons (L1s) and other genomic repeats, recruiting MORC2 effectors remodel chromatin. However, how HUSH operate alongside DNA methylation, a central epigenetic regulator repeat transcription, remains poorly understood. Here we interrogate this relationship in neural progenitor cells (hNPCs), somatic model brain development that tolerates removal methyltransferase DNMT1. Upon loss or subunit TASOR hNPCs,...
Abstract SVA retrotransposons remain active in humans and contribute to individual genetic variation. Polymorphic alleles harbor gene-regulatory potential can cause disease. However, how insertions are controlled functionally impact human disease is unknown. Here, we dissect the epigenetic regulation influence of SVAs cellular models X-linked dystonia-parkinsonism (XDP), a neurodegenerative disorder caused by an insertion at TAF1 locus. We demonstrate that KRAB zinc finger protein ZNF91...