A5026203926- Epigenetics and DNA Methylation
- Pluripotent Stem Cells Research
- CRISPR and Genetic Engineering
- RNA modifications and cancer
- Cancer-related gene regulation
- Atherosclerosis and Cardiovascular Diseases
- Renal and related cancers
- Tissue Engineering and Regenerative Medicine
- T-cell and B-cell Immunology
- Nitric Oxide and Endothelin Effects
- Acute Myeloid Leukemia Research
- Cancer-related molecular mechanisms research
- Genomics and Chromatin Dynamics
- Renin-Angiotensin System Studies
- Pelvic floor disorders treatments
- Genetic Syndromes and Imprinting
- Wnt/β-catenin signaling in development and cancer
- Genetics and Neurodevelopmental Disorders
- Urological Disorders and Treatments
- Cancer Cells and Metastasis
- Nerve injury and regeneration
- Single-cell and spatial transcriptomics
- Innovation Policy and R&D
- Myeloproliferative Neoplasms: Diagnosis and Treatment
- Cell Adhesion Molecules Research
KU Leuven
2015-2025
Baylor College of Medicine
2023-2024
Harvard University
2009-2013
University of California, Los Angeles
2013
Boston Children's Hospital
2010-2013
New York University
2010
University School
2010
Target (United States)
2010
National University Hospital
2007
Yale University
2004-2006
Methylation Mediation of cytosine bases, 5-methylcytosine (5mC), in DNA plays an important regulatory role mammalian genomes. patterns are often inherited across generations, but they can also be dynamic, suggesting that active demethylation pathways exist. One such pathway, best characterized plants, involves the removal 5mC base, and its replacement by C, via a repair mechanism. Kriaucionis Heintz (p. 929 , published online 16 April) now show that, as well genomes, there significant...
Rhabdomyosarcoma (RMS), the most common pediatric soft tissue sarcoma, arises in skeletal muscle and remains an undifferentiated state due to transcriptional post-transcriptional regulators. Among its subtypes, fusion-negative RMS (FN-RMS) accounts for majority of diagnoses population. MicroRNAs (miRNAs) are non-coding RNAs that modulate cell identity via regulation messenger (mRNAs). In this study, we identify miRNAs impacting FN-RMS identity, revealing miR-449a miR-340 as major regulators...
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...
Allograft vascular dysfunction predisposes to arteriosclerosis and graft loss. We examined how develops in transplanted human arteries response circulating allogeneic T cells vivo using immunodeficient murine hosts. Within 7–9 days, developed endothelial cell (EC) but remained sensitive exogenous NO. By 2 weeks, the grafts impaired contractility desensitization NO, both signs of VSMC dysfunction. These cell–dependent changes correlated with loss eNOS expression iNOS — latter predominantly...
The forkhead, winged-helix transcription factor FOXP3 is preferentially expressed in T regulatory (Treg) cells and critical for their immunosuppressive function. Mutations that abolish function lead to systemic autoimmunity mice humans. However, the manner by which recognizes cognate DNA elements unclear. Here we identify an vitro optimized sequence assess binding electrophoretic mobility shift assay (EMSA). contains two tandem copies of a core element resembling, but not identical to,...
The Tet 5-methylcytosine dioxygenases catalyze DNA demethylation by producing 5-hydroxymethylcytosine and further oxidized products. Tet1 Tet2 are highly expressed in mouse pluripotent cells downregulated to different extents somatic cells, but the transcriptional mechanisms unclear. Here we defined promoter enhancer domains Tet2. Within a 15-kb "superenhancer" of Tet1, there two transcription start sites (TSSs) with activation patterns during development. A 6-kb region upstream distal TSS...
Triple-Negative Breast Cancer (TNBC) is the most aggressive breast cancer subtype, characterized by limited treatment options and higher relapse rates than hormone-receptor-positive cancers. Chemotherapy remains mainstay for TNBC, platinum salts have been explored as a therapeutic alternative in neo-adjuvant metastatic settings. However, primary acquired resistance to chemotherapy general platinum-based regimens specifically strongly hampers TNBC management. In this study, we used...
In early mouse pre-implantation development, primitive endoderm (PrE) precursors are platelet-derived growth factor receptor alpha (PDGFRα) positive. Here, we demonstrated that cultured embryonic stem cells (mESCs) express PDGFRα heterogeneously, fluctuating between a PDGFRα+ (PrE-primed) and platelet endothelial cell adhesion molecule 1 (PECAM1)-positive state (epiblast-primed). The two surface markers can be co-detected on third subpopulation, expressing epiblast PrE determinants...
Abstract Gastrulation begins when the epiblast forms primitive streak or becomes definitive ectoderm. During this lineage bifurcation, DNA dioxygenase TET1 has bipartite functions in transcriptional activation and repression, but mechanisms remain unclear. By converting mouse embryonic stem cells (ESCs) into neuroprogenitors, we defined how Tet1–/– switch from neuroectoderm fate to form mesoderm endoderm. We identified Wnt repressor Tcf7l1 as a target that suppresses Wnt/β-catenin Nodal...
Background. Chronic allograft dysfunction may result from arterial injury, manifest as transplant arteriosclerosis (TA). This represents an important factor limiting long-term outcomes after heart and kidney transplantation; a relationship between acute injury TA has been suggested. We have used SCID/bg mice bearing transplanted human artery, inoculated with allogeneic PBMC to study arteriopathy in vessels. Earlier work demonstrated similar that observed clinically, identified interferon-γ...
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...
The etiology of neural tube defects (NTDs) involves complex gene-environmental interactions. Folic acid (FA) prevents NTDs, but the mechanisms remain poorly understood and at least 30% human NTDs resist beneficial effects FA supplementation. Here, we identify DNA demethylase TET1 as a nexus folate-dependent one-carbon metabolism genetic risk factors post-neural closure. We determine that cranial in
Gastrulation in the early postimplantation stage mammalian embryo begins when epiblast cells ingress to form primitive streak or develop as embryonic ectoderm. The DNA dioxygenase Tet1 is highly expressed and yet continues regulate lineage specification during gastrulation its expression diminished. Here, we show how plays a pivotal role upstream of germ layer bifurcation. During transition from naive pluripotency priming, global reconfiguration redistributes Oct4-cobound promoters distal...
Abstract Vaginal birth causes pelvic floor injury which may lead to urinary incontinence. Cell therapy has been proposed assist in functional recovery. We aim assess if intra-arterial injection of rat mesoangioblasts (MABs) and stable Vascular Endothelial Growth Factor (VEGF)-expressing MABs, improve recovery urethral vaginal function following simulated delivery (SVD). Female rats (n = 86) were assigned either saline (control), allogeneic-MABs (MABs allo ), autologous-MABs auto ) or...
Terminally differentiated cells are commonly regarded as the most stable cell state in adult organisms, characterized by growth arrest while fulfilling their specialized functions. A better understanding of mechanisms involved promoting cycle exit will improve ability to differentiate pluripotent into mature tissues for both pharmacological and therapeutic use. Here, it demonstrates that a hyperosmolar environment enforces protective p53-independent quiescent immature hepatoma stem...