A5052959084- Spaceflight effects on biology
- MicroRNA in disease regulation
- Immune Cell Function and Interaction
- RNA modifications and cancer
- Genetics, Aging, and Longevity in Model Organisms
- RNA Research and Splicing
- Single-cell and spatial transcriptomics
- T-cell and B-cell Immunology
- DNA Repair Mechanisms
- Telomeres, Telomerase, and Senescence
- Space Exploration and Technology
- Developmental Biology and Gene Regulation
- Tissue Engineering and Regenerative Medicine
- Genomics and Chromatin Dynamics
- Space Science and Extraterrestrial Life
- Fungal and yeast genetics research
- Toxin Mechanisms and Immunotoxins
- Cardiovascular Disease and Adiposity
- Congenital heart defects research
- Cancer-related molecular mechanisms research
- Mitochondrial Function and Pathology
- Glycosylation and Glycoproteins Research
- Birth, Development, and Health
- Angiogenesis and VEGF in Cancer
- Protein Kinase Regulation and GTPase Signaling
Spanish National Centre for Cardiovascular Research
2014-2025
Universidad Carlos III de Madrid
2024
Centro de Investigación en Red en Enfermedades Cardiovasculares
2022-2023
Centro Nacional de Investigaciones Científicas
2022
Consejo Superior de Investigaciones Científicas
1990-2015
Universidad Autónoma de Madrid
1996-2015
Instituto de Salud Carlos III
2010-2011
Centro Nacional de Biotecnología
2006-2011
Louisiana State University Health Sciences Center New Orleans
2004
Centro de Investigaciones Biológicas Margarita Salas
2003
In most clinical trials, human mesenchymal stem cells (hMSCs) are expanded in vitro before implantation. The genetic stability of is critical for their use. However, the relationship between stem-cell expansion and poorly understood. Here, we demonstrate that within normal period, hMSC cultures show a high percentage aneuploid progressively increases until senescence. Despite this accumulation, heterogeneous culture senescence-prone subpopulation has lower proliferation potential higher...
Abstract Tissue regeneration requires coordination between resident stem cells and local niche 1,2 . Here we identify that senescent are integral components of the skeletal muscle regenerative repress at all stages life. The technical limitation senescent-cell scarcity 3 was overcome by combining single-cell transcriptomics a enrichment sorting protocol. We identified isolated different cell types from damaged muscles young old mice. Deeper transcriptome, chromatin pathway analyses revealed...
Abstract Aims Epigenetic age is emerging as a personalized and accurate predictor of biological age. The aim this article to assess the association subclinical atherosclerosis with accelerated epigenetic investigate underlying mechanisms mediating association. Methods results Whole blood methylomics, transcriptomics, plasma proteomics were obtained for 391 participants Progression Early Subclinical Atherosclerosis study. was calculated from methylomics data each participant. Its divergence...
The amniote pallium contains sensory circuits that are structurally and functionally equivalent, yet their evolutionary relationship remains unresolved. We used birthdating analysis, single-cell RNA spatial transcriptomics, mathematical modeling to compare the development evolution of known pallial across birds (chick), lizards (gecko), mammals (mouse). reveal neurons within these circuits’ stations generated at varying developmental times brain regions species found an early divergence in...
Cardiac valve formation is crucial for embryonic and adult heart function. Valve malformations constitute the most common congenital cardiac defect, but little known about molecular mechanisms regulating homeostasis. Here, we show that endocardial Notch1 myocardial Bmp2 signal integration establish a valve-forming field between 2 chamber developmental domains. Patterning occurs through activation of epithelial-to-mesenchymal transition (EMT) exclusively in prospective territories. Mice with...
The yeast Saccharomyces cerevisiae has a limited life-span, which is measured by the number of divisions that individual cells complete. Among many changes occur as yeasts age are alterations in chromatin-dependent transcriptional silencing. We have genetically manipulated histone deacetylases to modify chromatin, and we examined effect on longevity. Deletion deacetylase gene RPD3 extended life-span. Its effects chromatin functional state were evidenced enhanced silencing at three known...
The polycystic ovary syndrome (PCOS) is frequently associated with visceral obesity, suggesting that omental adipose tissue might play an important role in the pathogenesis of syndrome.The objective was to study expression profiles fat biopsy samples obtained from morbidly obese women or without PCOS at time bariatric surgery.This a case-control study.We conducted academic hospital.Eight patients and seven nonhyperandrogenic submitted surgery because morbid obesity.Biopsy were during...
Activation-induced deaminase (AID) initiates antibody diversification in germinal center (GC) B cells through the deamination of cytosines on immunoglobulin genes. AID can also target other regions genome, triggering mutations or chromosome translocations, with major implications for oncogenic transformation. However, understanding specificity has proved extremely challenging. We have sequenced at very high depth >1,500 genomic from GC and identified 275 genes targeted by AID,...
Abstract Here we explored the role of interleukin-1β (IL-1β) repressor cytokine, IL-1 receptor antagonist (IL-1rn), in both healthy and abnormal hematopoiesis. Low IL-1RN is frequent acute myeloid leukemia (AML) patients represents a prognostic marker reduced survival. Treatments with IL-1β monoclonal antibody canakinumab reduce expansion leukemic cells, including CD34 + progenitors, AML xenografts. In vivo deletion IL-1rn induces hematopoietic stem cell (HSC) differentiation into lineage...
Mitochondrial dysfunction induces a signaling pathway, which culminates in changes the expression of many nuclear genes. This retrograde response, as it is called, extends yeast replicative life span. It also results marked increase cellular content extrachromosomal ribosomal DNA circles (ERCs), can cause demise cell. We have resolved conundrum how these two molecular mechanisms longevity operate tandem. About 50% life-span extension elicited by response involves processes other than those...
Infection with Mycobacterium tuberculosis (Mtb) can produce a wide spectrum of clinical manifestations, ranging from active (TB) to asymptomatic latent infection. Although CD4 T-cells are key immune effectors control TB, early after infection, the innate response must play role in tackling disease. Here, we performed in-depth analyses acute MTBVAC, candidate vaccine engineered Mtb aim protecting adults pulmonary TB disease, still major global challenge. scRNA-seq shows expansion CD4+ and...
We demonstrate in this report that the epidermal growth factor (EGF) receptor from rat liver can be isolated by calmodulin affinity chromatography binding presence of Ca2+ and elution with a Ca(2+)-chelating agent. The bulk EGF is not eluted NaCl gradient Ca2+. ascertained identity immunoblot immunoprecipitation using polyclonal antibody against an human origin. purified autophosphorylated tyrosine residues EGF-stimulated manner, EGF-dependent phosphorylation serine was also detected. Both...
We have reported that in vitro culture (IVC) of preimplantation mouse embryos the presence FCS produces long-term effects (LTE) on development, growth and behaviour offspring at adult age. To analyse mechanisms underlying this phenomenon, we examined development global alterations gene expression blastocysts produced FCS, conditions known to be suboptimal generate LTE. Embryos cultured KSOM KSOM+FCS had a reduced number cells inner cell mass blastocyst stage compared with vivo derived...
Methotrexate (MTX) functions as an antiproliferative agent in cancer and anti-inflammatory drug rheumatoid arthritis (RA). Although macrophages critically contribute to RA pathology, their response MTX remains unknown. As a means identify markers, we have explored its transcriptional effect on polarised by GM-CSF (GM-MØ) or M-CSF (M-MØ), which resemble proinflammatory found normal joints, respectively.The transcriptomic profile of both human macrophage subtypes exposed 50 nM under long-term...
Hutchinson-Gilford progeria syndrome (HGPS) is an extremely rare disease caused by the expression of progerin, aberrant protein produced a point mutation in LMNA gene. HGPS patients show accelerated aging and die prematurely mainly from complications atherosclerosis such as myocardial infarction, heart failure, or stroke. However, mechanisms underlying vascular pathology remain ill defined. We used single-cell RNA sequencing to characterize aorta progerin-expressing LmnaG609G/G609G mice...
Genome-wide transcriptional profiling shows that reducing gravity levels during Drosophila metamorphosis in the International Space Station (ISS) causes important alterations gene expression: a large set of differentially expressed genes (DEGs) are observed compared to 1g controls. However, preparation procedures for spaceflight and nonideal environmental conditions on board ISS subject organisms additional stresses demonstrably affect expression. Simulated microgravity experiments performed...
The ING family of tumor suppressor proteins controls several cellular functions relevant to antitumor protection, such as cell cycle control, apoptosis, senescence, or migration. are functionally linked the p53 pathway, and they participate in transcriptional control via recognition histone marks recruitment protein complexes with chromatin-modifying activity specific promoters. Here, we have investigated global effect ING1 gene regulation through genome-wide analysis expression profiles...