Biology subjects

Vieira Braga, F. A.

Publications and source records attributed to Vieira Braga, F. A..

3 recordsLinked to original sources

bioRxiv2026

Single-cell characterization of tumor immune landscapes in colorectal cancer humanized mice

Colorectal cancer (CRC) displays inter-patient heterogeneity in molecular tumor features and immune cell composition, which influence therapy response. Humanized immune system (HIS) mouse models offer a promising in vivo model to study human tumor-immune interactions, yet their ability to recapitulate the CRC tumor immune microenvironment at single-cell resolution remains incompletely defined. Here, we performed single-cell RNA sequencing of systemic and tumor-infiltrating human immune cells in HIS mice bearing human CRC tumors and benchmarked these data against reference datasets of healthy human spleens and primary CRC tumors. Major immune lineages and transcriptional programs characteristic of the human systemic immune compartment were identified, and HIS mouse tumors developed complex, human-like immune infiltrates. Tumor-infiltrating immune cells comprised diverse T cell, myeloid, natural killer, and B cell populations, including exhausted T cell states marked by expression of PDCD1, TIGIT, HAVCR2, LAG3, and CTLA4. We further demonstrate CRC consensus molecular subtype-associated spatial differences in immune infiltration. Collectively, our findings support the use of HIS mice as a relevant model for studying CRC immune landscapes and preclinical evaluation of immunomodulatory therapies.

cancer biology↗

bioRxiv2022

Single-cell transcriptomics reveals subset-specific metabolic profiles underpinning the bronchial epithelial response to flagellin

Respiratory epithelial cells line the airways and represent the first line of defense against respiratory pathogens. The cellular heterogeneity of the airway wall has only recently been recognized by single-cell analyses. Here, we leveraged single-cell RNA sequencing of primary human bronchial epithelial cells growing in air-liquid interface to determine cell-specific changes evoked by flagellin, a protein driving the motility of many mucosal pathogens. We detected seven cell clusters in the human epithelium, including ciliated cells, ionocytes and several states of basal and secretory cells, of which only inflammatory basal cells and inflammatory secretory cells showed a proportional increase in response to flagellin. Only inflammatory secretory cells showed evidence of metabolic reprogramming toward aerobic glycolysis, and inhibition of the mTOR pathway specifically reduced this subset, prevented this metabolic shift, and reduced inflammatory gene transcription in these cells. This study expands our knowledge of the airways immune response to flagellated pathogens to single cell resolution and defines a novel target to modulate mucosal immunity during bacterial infections.

immunology↗

bioRxiv2019

A cellular census of healthy lung and asthmatic airway wall identifies novel cell states in health and disease

Human lungs enable efficient gas exchange, and form an interface with the environment which depends on mucosal immunity for protection against infectious agents. Tightly controlled interactions between structural and immune cells are required to maintain lung homeostasis. Here, we use single cell transcriptomics to chart the cellular landscape of upper and lower airways and lung parenchyma in health. We report location-dependent airway epithelial cell states, and a novel subset of tissue-resident memory T cells. In lower airways of asthma patients, mucous cell hyperplasia is shown to stem from a novel mucous ciliated cell state, as well as goblet cell hyperplasia. We report presence of pathogenic effector Th2 cells in asthma, and find evidence for type-2 cytokines in maintaining the altered epithelial cell states. Unbiased analysis of cell-cell interactions identify a shift from airway structural cell communication in health to a Th2-dominated interactome in asthma.

immunology↗