A5013604041- Genomics and Chromatin Dynamics
- Pluripotent Stem Cells Research
- CRISPR and Genetic Engineering
- Lysosomal Storage Disorders Research
- RNA Research and Splicing
- Trypanosoma species research and implications
- Advanced Fluorescence Microscopy Techniques
- Epigenetics and DNA Methylation
- RNA Interference and Gene Delivery
- Chromatin Remodeling and Cancer
- Chromosomal and Genetic Variations
- Virus-based gene therapy research
- Cellular transport and secretion
- Tissue Engineering and Regenerative Medicine
- Protein Degradation and Inhibitors
- 3D Printing in Biomedical Research
- Renal and related cancers
- Genetics and Neurodevelopmental Disorders
- Retinal Development and Disorders
- RNA modifications and cancer
- Cell Image Analysis Techniques
- Neurogenesis and neuroplasticity mechanisms
- RNA and protein synthesis mechanisms
- Gene Regulatory Network Analysis
- Protein Kinase Regulation and GTPase Signaling
Centre for Genomic Regulation
2016-2025
Guangdong Academy of Medical Sciences
2023-2025
Southern Medical University
2023-2025
Guangdong Provincial People's Hospital
2023-2025
Institució Catalana de Recerca i Estudis Avançats
2016-2025
Universitat Pompeu Fabra
2016-2025
Guangzhou Institutes of Biomedicine and Health
2019-2023
Chinese Academy of Sciences
2020-2023
Guangzhou Regenerative Medicine and Health Guangdong Laboratory
2019-2023
FC Barcelona
2023
Abstract Chromatin organization is crucial for regulating gene expression. Previously, we showed that nucleosomes form groups, termed clutches. Clutch size correlated with the pluripotency grade of mouse embryonic stem cells and human induced pluripotent cells. Recently, it was also shown regions chromatin containing activating epigenetic marks were composed small dispersed nanodomains lower DNA density compared to larger silenced domains. Overall, these results suggest clutch may regulate...
Young mammals possess a limited regenerative capacity in some tissues, which is lost upon maturation. We investigated whether cellular senescence might play role such loss during liver regeneration. found that following partial hepatectomy, the senescence-associated genes p21, p16Ink4a, and p19Arf become dynamically expressed different cell types when decreases, but without full senescent response. However, we show treatment with senescence-inhibiting drug improves regeneration, by...
Nucleosomes form heterogeneous groups in vivo, named clutches. Clutches are smaller and less dense mouse embryonic stem cells (ESCs) compared to neural progenitor (NPCs). Using coarse-grained modeling of the pluripotency Pou5f1 gene, we show that genome-wide clutch differences between ESCs NPCs can be reproduced at a single gene locus. Larger formation is associated with changes compaction internucleosome contact probability fiber. single-molecule tracking (SMT), further core histone protein...
Abstract In interphase nuclei, chromatin forms dense domains of characteristic sizes, but the influence transcription and histone modifications on domain size is not understood. We present a theoretical model exploring this relationship, considering chromatin-chromatin interactions, modifications, extrusion. predict that heterochromatic governed by balance among diffusive flux methylated histones sustaining them acetylation reactions in process loop extrusion via supercoiling RNAPII at their...
Cell-fusion-mediated somatic-cell reprogramming can be induced in culture; however, whether this process occurs mammalian tissues remains enigmatic. Here, we show that upon activation of Wnt/β-catenin signaling, mouse retinal neurons transiently reprogrammed vivo back to a precursor stage. This after their spontaneous fusion with transplanted hematopoietic stem and progenitor cells (HSPCs). Moreover, demonstrate damage is essential for cell-hybrid formation vivo. Newly formed hybrids...
Vision impairments and blindness caused by retinitis pigmentosa result from severe neurodegeneration that leads to a loss of photoreceptors, the specialized light-sensitive neurons enable vision. Although mammalian nervous system is unable replace lost due degeneration, therapeutic approaches reprogram resident glial cells retinal have been proposed. Here, we demonstrate Müller glia can be reprogrammed in vivo into precursors then differentiate photoreceptors. We transplanted hematopoietic...
Abstract Early during preimplantation development and in heterogeneous mouse embryonic stem cells (mESC) culture, pluripotent are specified towards either the primed epiblast or primitive endoderm (PE) lineage. Canonical Wnt signaling is crucial for safeguarding naive pluripotency embryo implantation, yet role relevance of canonical inhibition early mammalian remains unknown. Here, we demonstrate that transcriptional repression exerted by Wnt/TCF7L1 promotes PE differentiation mESCs inner...
Most studies of cohesin function consider the Stromalin Antigen (STAG/SA) proteins as core complex members given their ubiquitous interaction with ring. Here, we provide functional data to support notion that SA subunit is not a mere passenger in this structure, but instead plays key role localization diverse biological processes and promotes loading at these sites. We show cells acutely depleted for RAD21, remain bound chromatin, cluster 3D interact CTCF, well wide range RNA binding...
Sulfatases are involved in several biological functions such as degradation of macromolecules the lysosomes. In patients with multiple sulfatase deficiency, mutations SUMF1 gene cause a reduction activities because posttranslational modification defect. We have generated mouse line carrying null mutation Sumf1 gene. Sulfatase completely absent Sumf1(-/-) mice, indicating that is indispensable for activation and mammals, differently from bacteria, single system. Similarly to deficiency...
Mucopolysaccharidosis type II (MPSII; Hunter syndrome) is a lysosomal storage disorder caused by deficiency in the enzyme iduronate 2-sulfatase (IDS). At present, therapeutic approaches for MPSII are replacement therapy and bone marrow transplantation, although these therapies have some limitations. The availability of new AAV serotypes that display tissue-specific tropism promote sustained expression transgenes offers possibility AAV-mediated gene systemic treatment diseases, including...
Sulfatases are enzymes that hydrolyse a diverse range of sulfate esters. Deficiency lysosomal sulfatases leads to human diseases characterized by the accumulation either GAGs (glycosaminoglycans) or sulfolipids. The catalytic activity resides in unique formylglycine residue their active site generated post-translational modification highly conserved cysteine residue. This is performed SUMF1 (sulfatase-modifying factor 1), which an essential for sulfatase activities. Mutations gene cause MSD...
Sulfatase modifying factor 1 (SUMF1) encodes for the formylglicine generating enzyme, which activates sulfatases by a key cysteine residue within their catalytic domains. SUMF1 is mutated in patients affected multiple sulfatase deficiency, rare recessive disorder all activities are impaired. Despite absence of canonical retention/retrieval signals, largely retained endoplasmic reticulum (ER), where it exerts its enzymatic activity on nascent sulfatases. Part secreted and paracrinally taken...
Cyclic activation of the Wnt/β-catenin signaling pathway controls cell fusion-mediated somatic reprogramming. TCFs belong to a family transcription factors that, in complex with β-catenin, bind and transcriptionally regulate Wnt target genes. Here, we show that needs be off during early reprogramming phases mouse embryonic fibroblasts (MEFs) into iPSCs. In MEFs undergoing reprogramming, senescence genes are repressed mesenchymal-to-epithelial transition is favored. This correlated repressive...