A5078408489- CRISPR and Genetic Engineering
- Pluripotent Stem Cells Research
- Animal Genetics and Reproduction
- Epigenetics and DNA Methylation
- Genetics and Neurodevelopmental Disorders
- Single-cell and spatial transcriptomics
- Genetic and Clinical Aspects of Sex Determination and Chromosomal Abnormalities
- Renal and related cancers
- Genomics and Chromatin Dynamics
- Silk-based biomaterials and applications
- Wound Healing and Treatments
- Pancreatic function and diabetes
- Periodontal Regeneration and Treatments
- Immune cells in cancer
- RNA Interference and Gene Delivery
- Genetic Syndromes and Imprinting
- Amyloidosis: Diagnosis, Treatment, Outcomes
- Virus-based gene therapy research
- Evolutionary Algorithms and Applications
- Trace Elements in Health
- Cancer Cells and Metastasis
- Reproductive Biology and Fertility
- Chromosomal and Genetic Variations
- Genetic and Kidney Cyst Diseases
- Research on Leishmaniasis Studies
KU Leuven
2018-2023
IMEC
2021
Stem Cell Institute
2019-2020
Medical University of Silesia
2015-2016
A hallmark of primate postimplantation embryogenesis is the specification extraembryonic mesoderm (EXM) before gastrulation, in contrast to rodents where this tissue formed only after gastrulation. Here, we discover that naive human pluripotent stem cells (hPSCs) are competent differentiate into EXM (EXMCs). EXMCs specified by inhibition Nodal signaling and GSK3B, maintained mTOR BMP4 activity, their transcriptome epigenome closely resemble monkey embryo EXM. mesenchymal, can arise from an...
Human naive pluripotent stem cells have unrestricted lineage potential. Underpinning this property, are thought to lack chromatin-based barriers. However, assumption has not been tested. Here we define the chromatin-associated proteome, histone post-translational modifications and transcriptome of human primed cells. Our integrated analysis reveals differences in relative abundance activities distinct chromatin modules. We identify a strong enrichment polycomb repressive complex 2...
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...
Induction and reversal of chromatin silencing is critical for successful development, tissue homeostasis, the derivation induced pluripotent stem cells (iPSCs). X-Chromosome inactivation (XCI) reactivation (XCR) in female represent chromosome-wide transitions between active inactive states. Although XCI has long been studied, providing important insights into gene regulation, dynamics mechanisms underlying stable X-linked genes are much less understood. Here, we use allele-specific...
Significance The pituitary is our master endocrine gland. Local damage and aging present important threats. We started to decrypt the ill-defined regulation of gland’s stem cells, typically dormant but acutely activated upon damage. Single-cell transcriptomics uncovered interleukin-6 as a cell activator local damage, corroborated in vivo vitro using cell–derived organoids. This competence extinguishes at aging, concurrent with raised inflammatory state older gland (inflammaging). However,...
Abstract Defective cell migration causes delayed wound healing (WH) and chronic skin lesions. Autologous micrograft (AMG) therapies have recently emerged as a new effective affordable treatment able to improve capacity. However, the precise molecular mechanism through which AMG exhibits its beneficial effects remains unrevealed. Herein we show that improves re-epithelialization by accelerating of fibroblasts keratinocytes. More specifically, AMG-treated wounds showed improvement...
Highlights•X-chromosome dosage modulates the pluripotent chromatin accessibility landscape•Increased X-chromosome slows down growth•Dusp9 heterozygous female ESCs display pluripotency exit delaySummaryReprogramming mouse somatic cells into induced stem (iPSCs) leads to reactivation. The extent which increased (X-dosage) in iPSCs compared with male differences properties of is still unclear. We show that modulated by X-dosage. Specific sets transcriptional regulator motifs are enriched XX or...
Abstract Background Precise gene dosage of the X chromosomes is critical for normal development and cellular function. In mice, XX female somatic cells show transcriptional chromosome upregulation their single active chromosome, while other inactive. Moreover, inactive reactivated during in inner cell mass germ through reactivation, which can be studied vitro by reprogramming to pluripotency. How chromatin processes regulatory networks evolved regulate state reactivation remains unclear....
ABSTRACT Reprogramming to induced pluripotency induces the switch of somatic cell identity pluripotent stem cells (iPSCs). However, mediators and mechanisms reprogramming remain largely unclear. To elucidate reprogramming, we used a siRNA-mediated knockdown approach for selected candidate genes during conversion into iPSCs. We identified Tox4 as novel factor that modulates fate through an assay determined efficiency iPSC reprogramming. found is needed early in efficiently generate...
Reprogramming somatic cells into induced pluripotent stem (iPSCs) involves the reactivation of endogenous pluripotency genes and global DNA demethylation, but temporal resolution these events using existing markers is limited. Here, we generate murine transgenic lines harboring reporters for 5-methylcytosine dioxygenase Tet1 Oct4. By monitoring dual reporter fluorescence during entry, identify a sequential order Oct4 activation by proximal distal regulatory elements. Full marks an...
Abstract Cellular identity during development is under the control of transcription factors that form gene regulatory networks. However, and networks underlying cellular in human adult pancreas remain largely unexplored. Here, we integrate multiple single-cell RNA-sequencing datasets pancreas, totaling 7393 cells, comprehensively reconstruct We show a network 142 forms distinct modules characterize pancreatic cell types. present evidence our approach identifies regulators states pancreas....
ABSTRACT Background Induction and reversal of chromatin silencing is critical for successful development, tissue homeostasis the derivation induced pluripotent stem cells (iPSCs). X-chromosome inactivation (XCI) reactivation (XCR) in female represent chromosome-wide transitions between active inactive states. While XCI has long been studied provided important insights into gene regulation, dynamics mechanisms underlying stable X-linked genes are much less understood. Here, we use...
SUMMARY Cellular identity during development is under the control of transcription factors that form gene regulatory networks. However, and networks underlying cellular in human adult pancreas remain largely unexplored. Here, we integrate multiple single-cell RNA-sequencing datasets pancreas, totaling 7393 cells, comprehensively reconstruct We show a network 142 forms distinct modules characterize pancreatic cell types. present evidence our approach identifies regulators pancreas. predict...
Abstract Defective fibroblast migration causes delayed wound healing (WH) and chronic skin lesions. Autologous micrograft (AMG) therapies have recently emerged as a new effective treatment able to improve capacity. However, the molecular mechanisms connecting their beneficial outcomes with process are still unrevealed. Here, we show that AMG modulates primary accelerates re-epithelialization without affecting cell proliferation. We demonstrate is enriched in pool of WH-associated growth...
ABSTRACT During early mammalian development, the two X-chromosomes in female cells are active. Dosage compensation between XX and XY male is then achieved by X-chromosome inactivation cells. Reprogramming mouse somatic into induced pluripotent stem (iPSCs) leads to reactivation. The extent which increased dosage (X-dosage) iPSCs differences molecular cellular properties of still unclear. We show that chromatin accessibility modulated X-dosage. Specific sets transcriptional regulator motifs...
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...
Abstract The generation of induced pluripotent stem cells (iPSCs) involves activation the endogenous pluripotency circuitry and global DNA demethylation late in reprogramming, but temporal resolution these events using existing markers is insufficient. Here, we generated murine transgenic lines harboring dual fluorescent reporters reflecting cell-state specific expression master factor Oct4 5-methylcytosine dioxygenase Tet1 . By assessing reprogramming intermediates based on reporter...
The generation of induced pluripotent stem cells (iPSCs) involves activation the endogenous pluripotency circuitry and global DNA demethylation late in reprogramming, but temporal resolution these events using existing markers is insufficient. Here, we generated murine transgenic lines harboring dual fluorescent reporters reflecting cell-state specific expression master factor Oct4 5-methylcytosine dioxygenase Tet1. By assessing reprogramming intermediates based on reporter patterns,...