A5004220955- Single-cell and spatial transcriptomics
- Immune Cell Function and Interaction
- T-cell and B-cell Immunology
- interferon and immune responses
- Immunotherapy and Immune Responses
- RNA Research and Splicing
- IL-33, ST2, and ILC Pathways
- Liver physiology and pathology
- RNA modifications and cancer
- Gut microbiota and health
- Pancreatic and Hepatic Oncology Research
- Neurogenesis and neuroplasticity mechanisms
- RNA regulation and disease
- RNA and protein synthesis mechanisms
- Neuroinflammation and Neurodegeneration Mechanisms
- Congenital gastrointestinal and neural anomalies
- Cancer-related molecular mechanisms research
- Cancer Cells and Metastasis
- Viral Infections and Vectors
- Cancer Genomics and Diagnostics
- CAR-T cell therapy research
- Protist diversity and phylogeny
- Genomics and Phylogenetic Studies
- Parvovirus B19 Infection Studies
- Angiogenesis and VEGF in Cancer
University of Lisbon
2015-2025
ETH Zurich
2021-2024
Wellcome Sanger Institute
2017-2022
Droplet-based single-cell RNA sequencing protocols have dramatically increased the throughput of transcriptomics studies. A key computational challenge when processing these data is to distinguish libraries for real cells from empty droplets. Here, we describe a new statistical method calling droplet-based data, based on detecting significant deviations expression profile ambient solution. Using simulations, demonstrate that EmptyDrops has greater power than existing approaches while...
Despite their crucial role in health and disease, our knowledge of immune cells within human tissues remains limited. We surveyed the compartment 16 from 12 adult donors by single-cell RNA sequencing VDJ generating a dataset ~360,000 cells. To systematically resolve cell heterogeneity across tissues, we developed CellTypist, machine learning tool for rapid precise type annotation. Using this approach, combined with detailed curation, determined tissue distribution finely phenotyped types,...
Transcription is a highly dynamic process. Consequently, we have developed native elongating transcript sequencing technology for mammalian chromatin (mNET-seq), which generates single-nucleotide resolution, nascent transcription profiles. Nascent RNA was detected in the active site of polymerase II (Pol II) along with associated processing intermediates. In particular, 5′splice cleavage by spliceosome, showing that cleaved upstream exon transcripts are Pol CTD phosphorylated on serine 5...
Non-lymphoid tissues (NLTs) harbor a pool of adaptive immune cells with largely unexplored phenotype and development. We used single-cell RNA-seq to characterize 35,000 CD4+ regulatory (Treg) memory (Tmem) T in mouse skin colon, their respective draining lymph nodes (LNs) spleen. In these tissues, we identified Treg cell subpopulations distinct degrees NLT phenotype. Subpopulation pseudotime ordering gene kinetics were consistent recruitment yet the initial NLT-priming LNs final stages...
Human gut development requires the orchestrated interaction of differentiating cell types. Here, we generate an in-depth single-cell map developing human intestine at 6-10 weeks post-conception. Our analysis reveals transcriptional profile cycling epithelial precursor cells; distinct from LGR5-expressing cells. We propose that these cells may contribute to differentiated subsets via generation stem and receive signals surrounding mesenchymal Furthermore, draw parallels between transcriptomes...
T helper type 2 (Th2) cells are important regulators of mammalian adaptive immunity and have relevance for infection, autoimmunity, tumor immunology. Using a newly developed, genome-wide retroviral CRISPR knockout (KO) library, combined with RNA-seq, ATAC-seq, ChIP-seq, we dissected the regulatory circuitry governing activation differentiation these cells. Our experiments distinguish cell versus in quantitative framework. We demonstrate that two processes tightly coupled jointly controlled...
Salamanders are tetrapod models to study brain organization and regeneration; however, the identity evolutionary conservation of cell types largely unknown. We delineated populations in axolotl telencephalon during homeostasis regeneration using single-cell genomic profiling. identified glutamatergic neurons with similarities amniote hippocampus, dorsal lateral cortex, conserved γ-aminobutyric acid-releasing (GABAergic) neuron classes. inferred transcriptional dynamics gene regulatory...
The highly intronic nature of protein coding genes in mammals necessitates a co-transcriptional splicing mechanism as revealed by mNET-seq analysis. Immunoprecipitation MNase-digested chromatin with antibodies against RNA polymerase II (Pol II) shows that active spliceosomes (both snRNA and proteins) are complexed to Pol S5P CTD during elongation splicing. Notably, elongating II-spliceosome complexes form strong interactions nascent transcripts, resulting footprints approximately 60...
The IRE1a-XBP1 pathway is a conserved adaptive mediator of the unfolded protein response. indispensable for development secretory cells by facilitating folding and enhancing capacity. In immune system, it known to function in dendritic cells, plasma eosinophil differentiation, while its role T helper cell unexplored. Here, we investigated regulating activation differentiation type-2 (Th2), major type involved allergy, asthma, helminth infection, pregnancy, tumor immunosuppression.We...
Abstract Several drugs targeting members of the TNF superfamily or receptor (TNFRSF) are widely used in medicine currently being tested therapeutic trials. However, their mechanism action remains poorly understood. Here, we explored effects TNFRSF co‐stimulation on murine Foxp3 + regulatory T cell (Treg) biology, as they pivotal modulators immune responses. We show that engagement TNFR2, 4‐1BB, GITR, and DR3, but not OX40, increases Treg proliferation survival. Triggering these Tregs induces...
Abstract The liver has the remarkable capacity to regenerate. In clinic, regeneration is induced by portal vein embolization, which redirects blood flow, resulting in hypertrophy locations with increased supply, and atrophy of embolized segments. Here, we apply single-cell single-nucleus transcriptomics on healthy, hypertrophied, atrophied patient-derived samples explore cell states regenerating liver. Our data unveils pervasive upregulation genes associated developmental processes, cellular...
Abstract Bats have adapted to pathogens through diverse mechanisms, including increased resistance – rapid pathogen elimination, and tolerance limiting tissue damage following infection. In the Egyptian fruit bat (an important model in comparative immunology) several mechanisms conferring disease were discovered, but underpinning remain poorly understood. Previous studies on other species suggested that elevated basal expression of innate immune genes may lead Here, we test whether such...
Abstract The crucial capability of T cells for discrimination between self and non-self peptides is based on negative selection developing thymocytes by medullary thymic epithelial (mTECs). mTECs purge autoreactive expression cell-type specific genes referred to as tissue-restricted antigens (TRAs). Although the autoimmune regulator (AIRE) protein known promote a subset TRAs, its mechanism action still not fully understood. TRAs that are under control AIRE also needs further...
Plasmacytoid dendritic cells (pDCs) produce type I interferon (IFN-I) and are traditionally defined as being BDCA-2+CD123+. pDCs not readily detectable in healthy human skin, but have been suggested to accumulate wounds. Here, we describe a CD1a-bearing BDCA-2+CD123int DC subset that rapidly infiltrates skin wounds comprises major population. Using single-cell RNA sequencing, show these largely activated DCs acquiring features compatible with lymph node homing antigen presentation,...
Transcriptomics supports that human T reg cells differentiate into mature lymphoid tissue or circulating follicular regulatory cells.
For a future doctor it is essential to know the pathophysiology of diseases that affect their patients, so they perform efficient care and if do not find cure leave least possible damage with best quality life. Although anosmia mild symptom among patients affected by Covid 19, brings consequences on life individual. Even being pathology be clarified in several points despite leads, can lead patient compromise other areas, such as psychological. We must bear mind every human bio-psycho-social...