55 documents found, page 1 of 6
Will Spatial Transcriptomics Transform Pathology?
Cristovão, Miguel; Carmo-Fonseca, Maria; Alves-Vale, CatarinaSpatial transcriptomics (ST) is an emerging technology that maps gene expression directly onto tissue architecture. As it moves toward clinical adoption, ST is poised to become an integral tool in precision diagnostics. Here, we discuss its potential to complement and enhance traditional morphological assessment, reinforcing the pathologist’s central role in the molecular era.; A transcriptómica espacial (TE) é...
Generation of induced pluripotent stem cell lines from two unrelated individual...
Ribeiro, Marta; Martins, Sandra; Carvalho, Teresa; Furtado, Marta; Cabral, Joaquim M.S.; Brito, Dulce; Carmo-Fonseca, Maria; da Rocha, Simão T.Familial hypertrophic cardiomyopathy (HCM) is the most common inherited heart condition. HCM patients show left ventricle hypertrophy without any associated loading conditions, being at risk for heart failure and sudden cardiac death. Two induced pluripotent stem cell (iPSC) lines were generated from peripheral blood mononuclear cells obtained from two unrelated individuals, a 54-year-old male (F81) and a 44-ye...
Genetic modulation of RNA splicing rescues BRCA2 function in mutant cells
Lima, Beatriz Anjo; Pais, Ana Carolina; Dupont, Juliette; Dias, Patrícia; Custódio, Noélia; Sousa, Ana Berta; Carmo-Fonseca, Maria; Carvalho, CéliaVariants in the hereditary cancer-associated BRCA1 and BRCA2 genes can alter RNA splicing, producing transcripts that encode internally truncated yet potentially functional proteins. However, few studies have quantitatively analyzed variant-specific splicing isoforms. Here, we investigated cells heterozygous and homozygous for the BRCA2:c.681+5G>C variant. Using droplet digital RT-PCR, we identified two variant...
RP-10 LESSONS FROM THE COVID-19 PANDEMIC: STUDENT EVALUATION OF A NEWLY IMPLEME...
Velha, António; Custódio, Noélia; Carmo-Fonseca, Maria; Patrício, MadalenaIntroduction and goal As the COVID-19 pandemic flooded the world throughout the first half of 2020, medical schools were faced with a choice: swim or die – learning shifted radically online as countries went into lockdown. With the easing of restrictions, the Molecular and Cellular Biology (MCB) course at FMUL introduced a flipped classroom approach during semester I, based on pre-recorded lectures followed by ...
A twist to splicing regulation in haematopoiesis
Carmo-Fonseca, MariaDNMT3A is best known for its de novo DNA methyltransferase activity. But a new study shows that the protein also has a role in RNA splicing during activation of embryonic and haematopoietic stem cells. This introduces a new perspective for approaching diseases associated with DNMT3A mutations.
Sweet splicing
Carmo-Fonseca, MariaGlucose is the main source of energy for cells. In this issue of Cell, a study now shows that glucose has additional non-energetic functions, acting as a biomolecular cue that regulates alternative splicing during epidermal differentiation. As keratinocytes differentiate, glucose associates with RNA-binding protein DDX21 and modulates its interaction properties, which modifies splicing decisions.
Expression profiling in ovarian cancer reveals coordinated regulation of BRCA1/...
Custódio, Noélia; Savisaar, Rosina; Carvalho, Célia; Bak-Gordon, Pedro; Ribeiro, Maria I.; Almeida-Tavares, Joana; Nunes, Paula B.; Peixoto, CarolinaPredictive biomarkers are crucial in clarifying the best strategy to use poly(ADP-ribose) polymerase inhibitors (PARPi) for the greatest benefit to ovarian cancer patients. PARPi are specifically lethal to cancer cells that cannot repair DNA damage by homologous recombination (HR), and HR deficiency is frequently associated with BRCA1/2 mutations. Genetic tests for BRCA1/2 mutations are currently used in the cl...
Comprehensive genomic profiling of cell-free circulating tumor DNA detects resp...
Silveira, Catarina; Sousa, Ana Carla; Corredeira, Patrícia; Martins, Marta; Sousa, Ana Rita; Da Cruz Paula, Arnaud; Selenica, Pier; Brown, David N.Analysis of cell-free circulating tumor DNA obtained by liquid biopsy is a non-invasive approach that may provide clinically actionable information when conventional tissue biopsy is inaccessible or infeasible. Here, we followed a patient with hormone receptor-positive and human epidermal growth factor receptor (HER) 2-negative breast cancer who developed bone metastases seven years after mastectomy. We analyze...
Smaug1 membrane-less organelles respond to AMPK and mTOR and affect mitochondri...
Fernández-Alvarez, Ana J.; Gabriela Thomas, María; Pascual, Malena L.; Habif, Martín; Pimentel, Jerónimo; Corbat, Agustín A.; Pessoa, JoãoSmaug is a conserved translational regulator that binds numerous mRNAs, including nuclear transcripts that encode mitochondrial enzymes. Smaug orthologs form cytosolic membrane-less organelles (MLOs) in several organisms and cell types. We have performed single-molecule fluorescence in situ hybridization (FISH) assays that revealed that SDHB and UQCRC1 mRNAs associate with Smaug1 bodies in U2OS cells. Loss of f...
Transcription and splicing dynamics during early Drosophila development
Prudêncio, Pedro; Savisaar, Rosina; Rebelo, Kenny; Martinho, Rui Goncalo; Carmo-Fonseca, MariaWidespread cotranscriptional splicing has been demonstrated from yeast to human. However, most studies to date addressing the kinetics of splicing relative to transcription used either Saccharomyces cerevisiae or metazoan cultured cell lines. Here, we adapted native elongating transcript sequencing technology (NET-seq) to measure cotranscriptional splicing dynamics during the early developmental stages of Droso...