Biology subjects

Denadai-Souza, A.

Publications and source records attributed to Denadai-Souza, A..

3 recordsLinked to original sources

bioRxiv2026

The Human Gut Cell Atlas v1.0: A Unified, Community-BuiltReference of Cellular Diversity Across the Gut

Single-cell RNA-sequencing (scRNA-seq) studies have transformed our understanding of cellular diversity in the human intestine, but differences in anatomical sampling, experimental processing and cell-type nomenclature limit comparison across datasets. Here, we present the Human Gut Cell Atlas (HGCA) V1, a community-curated reference of 944,390 healthy and disease-adjacent intestinal cells from 502 samples, 265 donors and 24 landmark studies, linked to detailed anatomical, clinical, and technical metadata. As this metadata is of critical importance to human biology, we developed MetaManager, an open source data management framework for standardized metadata collection and tracking. A five-level consensus taxonomy resolves 94 homeostatic cell identities and enables transferrable, high-resolution annotation of new gut datasets. By assembling cell identity, sampling metadata, and independent spatial validation, intestinal segment and radial tissue depth were revealed to systematically shape cellular composition and transcriptional state, enabling inference of the presence of sampling-dependent tissue niches, including lymphoid follicles. Reference mapping accurately and rapidly recovered cohort-level Crohn's disease and treatment signatures without de novo annotation, while mapping human intestinal organoids quantified cell-type-specific identity, regional specification, maturation, and transcriptional fidelity to native tissue. The HGCA V1 provides a standardized cellular, anatomical coordinate, and metadata system for reproducible, high-quality analysis of intestinal biology across healthy tissue, disease-associated remodelling, and experimental models, providing a continuously evolving community reference for cumulative discovery in human intestinal biology.

systems biology↗

bioRxiv2026

Cirrhosis-associated immune dysfunction presents with preserved circulating lymphocyte function and altered intestinal intraepithelial lymphocyte profile

Bacterial infections are major drivers of decompensation and mortality in cirrhosis, yet the mechanisms underlying cirrhosis-associated immune dysfunction remain incompletely understood. Although current models frequently invoke adaptive immune exhaustion, intestinal intraepithelial lymphocytes (IELs), a central barrier immune compartment responsible for epithelial surveillance and microbial containment, have remained largely unexplored in cirrhosis. Here, we performed integrated immune profiling of paired duodenal biopsies and peripheral blood from healthy volunteers and patients with compensated or decompensated cirrhosis using spectral flow cytometry, plasma proteomics, immunofluorescence, and single-cell RNA sequencing. The healthy duodenal epithelium was dominated by CD8{beta} IELs, whereas cirrhosis was associated with marked depletion of these cells together with expansion of innate cytotoxic populations. Residual IELs exhibited attenuation of antimicrobial transcriptional programs alongside enrichment of innate-like cytotoxic pathways. Loss of CD8{beta} IELs was associated with coordinated reduction of CCR9 surface expression across circulating and mucosal CD8 T-cell compartments together with persistent systemic elevation of CCL25. In contrast, circulating lymphocytes retained functional competence and lacked enrichment of canonical exhaustion markers despite progressive inflammatory remodeling. Collectively, these findings identify defective intestinal IEL compartmentalization as a central feature of cirrhosis-associated immune dysfunction and implicate dysregulation of the CCL25-CCR9 axis in impaired mucosal immune surveillance. HighlightsO_LICirrhosis-associated immune dysfunction reflects defective mucosal immune compartmentalization rather than global adaptive immune paralysis C_LIO_LICirculating lymphocytes retain effector function and do not exhibit canonical exhaustion phenotypes C_LIO_LICD8{beta} intraepithelial lymphocytes are selectively depleted from the duodenal epithelium in cirrhosis C_LIO_LIPersistent systemic CCL25 elevation is associated with coordinated CCR9 loss across mucosal and circulating CD8 T-cell compartments C_LI

immunology↗

bioRxiv2022

Spatially resolved transcriptomic profiling of degraded and challenging fresh frozen samples

Spatially resolved transcriptomics (SRT) has enabled precise genome-wide mRNA expression profiling within tissue sections. The performance of unbiased SRT methods targeting the polyA tail of mRNA, relies on the availability of specimens with high RNA quality. Moreover, the high cost of currently available SRT assays requires a careful sample screening process to increase the chance of obtaining high-quality data. Indeed, the upfront analysis of RNA quality can show considerable variability due to sample handling, storage, and/or intrinsic factors. We present RNA-Rescue Spatial Transcriptomics (RRST), an SRT workflow designed to improve mRNA recovery from fresh frozen (FF) specimens with moderate to low RNA quality. First, we provide a benchmark of RRST against the standard Visium spatial gene expression protocol on high RNA quality samples represented by mouse brain and prostate cancer samples. Then, we demonstrate the RRST protocol on tissue sections collected from 5 challenging tissue types, including: human lung, colon, small intestine, pediatric brain tumor, and mouse bone/cartilage. In total, we analyzed 52 tissue sections and our results demonstrate that RRST is a versatile, powerful, and reproducible protocol for FF specimens of different qualities and origins.

genomics↗