A5006245775- Developmental Biology and Gene Regulation
- RNA Research and Splicing
- Microtubule and mitosis dynamics
- Cancer-related molecular mechanisms research
- Immunodeficiency and Autoimmune Disorders
- Genomics and Chromatin Dynamics
- Pluripotent Stem Cells Research
- Epigenetics and DNA Methylation
- MicroRNA in disease regulation
- Neurogenesis and neuroplasticity mechanisms
- Neonatal Respiratory Health Research
- Immune Cell Function and Interaction
- Plant Molecular Biology Research
- RNA modifications and cancer
- T-cell and B-cell Immunology
- Natural Antidiabetic Agents Studies
- Latin American Cultural Politics
- interferon and immune responses
- Pancreatic function and diabetes
- Congenital heart defects research
- Extracellular vesicles in disease
- Cancer-related gene regulation
- Cellular Mechanics and Interactions
- Platelet Disorders and Treatments
- Indigenous Cultures and History
University of Lisbon
2018-2024
Instituto Gulbenkian de Ciência
2014-2021
Centro Hospitalar Lisboa Norte
2019
Instituto de Medicina Molecular João Lobo Antunes
2019
Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo
2013
The Gurdon Institute
2007-2012
University of Cambridge
2007-2012
Medical University of Vienna
2009
Wellcome Trust
2007
The proneural transcription factor Ascl1 coordinates gene expression in both proliferating and differentiating progenitors along the neuronal lineage. Here, we used a cellular model of neurogenesis to investigate how interacts with chromatin landscape regulate when promoting differentiation. We find that binding occurs mostly at distal enhancers is associated activation transcription. Surprisingly, accessibility its sites neural stem/progenitor cells remains largely unchanged throughout...
Mutants in the actin nucleators Cappuccino and Spire disrupt polarized microtubule network Drosophila oocyte that defines anterior-posterior axis, suggesting organization depends on actin. Here, we show organize an isotropic mesh of filaments cytoplasm. capu spire mutants lack this mesh, whereas overexpressed truncated stabilizes presence Latrunculin A partially rescues mutants. overexpression cannot rescue mutants, but prevents disassembly at stage 10B blocks late cytoplasmic streaming. We...
Pull Me-No!-Push You The Drosophila dorsal-ventral (DV) axis is polarized by the movement of nucleus from posterior end oocyte to its anterior margin. It has long been assumed that pulled molecular motor dynein along microtubule cytoskeleton defines anterior-posterior (AP) axis. Using live imaging, Zhao et al. (p. 999, published online 12 April; see Perspective Bowerman and O'Rourke ) now demonstrate pushed toward force exerted growing microtubules hitting side. DV polarity thus depends on...
Centrosome asymmetry plays a key role in ensuring the asymmetric division of Drosophila neural stem cells (neuroblasts [NBs]) and male germline (GSCs) [1Rebollo E. Sampaio P. Januschke J. Llamazares S. Varmark H. Gonzalez C. Functionally unequal centrosomes drive spindle orientation asymmetrically dividing cells.Dev. Cell. 2007; 12: 467-474Abstract Full Text PDF PubMed Scopus (234) Google Scholar, 2Yamashita Y.M. Mahowald A.P. Perlin J.R. Fuller M.T. Asymmetric inheritance mother versus...
In the developing mammalian brain, differentiating neurons mature morphologically via neuronal polarity programs. Despite discovery of pathways acting concurrently with differentiation, it's unclear how traverse complex transitions or progenitors delay polarization during development. We report that zinc finger and homeobox transcription factor-1 (Zeb1), a master regulator epithelial polarity, controls differentiation by transcriptionally repressing genes in progenitors....
The generation of neurons from neural stem cells requires large-scale changes in gene expression that are controlled to a large extent by proneural transcription factors, such as Ascl1. While recent studies have characterized the differentiation genes activated less is known on mechanisms suppress progenitor cell identity. Here, we show Ascl1 induces factor MyT1 while promoting neuronal differentiation. We combined functional during neurogenesis with characterization its transcriptional...
Thymically committed regulatory CD4 T cells (tTregs) are essential for immune homeostasis and self-tolerance. We established the human tTreg Expression Signature by comparing genome-wide transcriptomic profiles between tTregs their conventional counterparts (tTconvs). further exploited high sequencing depth of our bulk RNA-seq data to identify a subset 250 genes significantly expressed in with neglectable expression tTconvs, defined as below levels IL2RA , that we named thymic Treg “private”...
Neurons of the mammalian neocortex are produced by proliferating cells located in ventricular zone (VZ) lining lateral ventricles. This is a complex and sequential process, requiring precise control cell cycle progression, fate commitment differentiation. We have analyzed publicly available databases from mouse human to identify candidate genes that potentially involved regulating early neocortical development neurogenesis. used situ hybridization dataset (The Allen Institute for Brain...
Abstract Background Loss of β ‐cell function hastens deterioration metabolic control in type 2 diabetes patients. Besides amyloid deposit and glucolipotoxicity, advanced glycation end products (AGEs) acting through their receptors (RAGE) seem to contribute this process by promoting islet apoptosis. In order investigate the role AGEs deterioration, we evaluated temporal dose effects AGE compounds on apoptosis rate, reactive oxygen species generation expression pro‐apoptotic anti‐apoptotic...
Computational strategies to extract meaningful biological information from multiomics data are in great demand for effective clinical use, particularly complex immune-mediated disorders. Regulatory T cells (Tregs) essential immune homeostasis and self-tolerance, controlling inflammatory autoimmune processes many diseases with a multigenic basis. Here, we quantify the Transcription Factor (TF) differential occupancy landscape uncover Gene Modules governing lineage-committed Tregs human...
Monozygotic twins provide a unique opportunity to better understand complex genetic diseases and the relative contribution of heritable factors in shaping immune system throughout life. Common Variable Immunodeficiency Disorders (CVID) are primary antibody defects displaying wide phenotypic heterogeneity, with monogenic transmission accounting for only minority cases. Here, we report pair monozygotic concordant CVID without family history immunodeficiency. They featured remarkably similar...
The spinal cord dorsal horn is a major station for integration and relay of somatosensory information comprises both excitatory inhibitory neuronal populations. homeobox gene Tlx3 acts as selector to control the development late-born (dILB) neurons by specifying glutamatergic transmitter fate in cord. However, since direct transcriptional targets remain largely unknown, it remains be uncovered how functions promote cell fate. Here we combined genomics approach based on chromatin...
Adaptation to breathing is a critical step in lung function and it crucial for organismal survival. Alveoli are the gas exchange units their development, from late embryonic early postnatal stages, requires feedbacks between multiple cell types. However, how crosstalk alveolar types modulated anticipate adaptation still unclear. Here, we uncovered synchronous alternative splicing switch genes developing mouse lungs at transition birth, identified hnRNP A1, Cpeb4, Elavl2/HuB as putative...
ABTRACT Computational strategies to extract meaningful biological information from multiomics data are in great demand for effective clinical use. This is most relevant immune-mediated disorders, where the combined impact of multiple variants difficult determine. Regulatory T cells (Tregs), particularly those lineage-committed thymus, essential immune homeostasis and self-tolerance, controlling inflammatory autoimmune processes many diseases with a multigenic basis. Here, we quantify...
Citrullination, the deimination of arginine residues into citrulline, has been implicated in aetiology several diseases. In multiple sclerosis (MS), citrullination is thought to be a major driver pathology, through hypercitrullination and destabilization myelin. As such, inhibition suggested as therapeutic strategy for MS. Here, contrast, we show by peptidylarginine deiminase 2 (PADI2) required normal oligodendrocyte differentiation, myelination motor function. We identify targets PADI2,...
Abstract Gas exchanges are ensured by lung alveoli, which mainly composed epithelial alveolar type 1 (AT1), 2 (AT2) and capillary endothelial cells (ECs). Alveologenesis starts during late embryonic development continues after birth relies on extensive biochemical crosstalk between these cell types. How this is modulated to anticipate accommodate the radical changes occurring at still unclear. We investigated alternative splicing (AS) postnatal transition performing RNAseq of mouse lungs...