Biology subjects

Nieto, J. C.

Publications and source records attributed to Nieto, J. C..

4 recordsLinked to original sources

bioRxiv2023

Quantifying Adaptive Evolution of the Human Immune Cell Landscape

The human immune system is under constant evolutionary pressure, primarily through its role as first line of defence against pathogens. Accordingly, population genomics studies have shown that immune-related genes have a high rate of adaptive evolution. These studies, however, are mainly based on protein-coding genes without cellular context, leaving the adaptive role of cell types and states uncharted. Inferring the rate of protein-coding genes adaptation in developing and adult immune cells at cellular resolution, we found cell types from both the lymphoid and myeloid compartments to harbour significantly increased adaptation rates. Specific cell states, such as foetal Pre-Pro B cells and adult T resident memory CD8+ cells show highly elevated rates of adaptation. We further analysed activated cell states, specifically, iPSC-derived macrophages responding to various challenges, including pro- and anti-inflammatory cytokines or bacterial and viral infections, the latter simulating the evolutionary arms race between humans and pathogens. Here, we found positive selection to be concentrated in early immune responses, suggesting benefits for the host to adapt to early stages of infection to control pathogen numbers and spread. Together, our study reveals spatio-temporal and functional biases in human immune populations with evidence of rapid adaptive evolution and provides a retrospect of forces that shaped the complexity, architecture, and function of the human body.

immunology↗

bioRxiv2023

FixNCut: Single-cell genomics through reversible tissue fixation and dissociation

The use of single-cell technologies for clinical applications requires disconnecting sampling from downstream processing steps. Early sample preservation can further increase robustness and reproducibility by avoiding artifacts introduced during specimen handling. We present FixNCut, a methodology for the reversible fixation of tissue followed by dissociation that overcomes current limitations. We applied FixNCut to human and mouse tissues to demonstrate the preservation of RNA integrity, sequencing library complexity, and cellular composition, while diminishing stress-related artifacts. Besides single-cell RNA sequencing, FixNCut is compatible with multiple single-cell and spatial technologies, making it a versatile tool for robust and flexible study designs.

bioinformatics↗

bioRxiv2023

Multi-organ single-cell transcriptomics of immune cells uncovered organ-specific gene expression and functions

Despite the large number of publicly available single-cell datasets, there is a limited understanding of the distinct resident immune cells and their concomitant features in diverse human organs. To address this, we compiled a dataset of 114,275 CD45+ immune cells from 14 organs from healthy donors. Although the transcriptome of immune cells is constant across organs, organ-specific gene expression changes were detected revealing unique expression in certain organs (GTPX3 in kidney, DNTT and ACVR2B in thymus). These alterations are associated with different transcriptional factor activities and pathways including metabolism. TNF- signaling through the NFkB pathway was found in various organs and immune compartments including distinct expression profiles of NFkB family genes and their target genes such as cytokines indicating their role in cell positioning. Taken together, immune cells not only protect the organs but also adapt to the host organ environment and contribute to its function and homeostasis.

immunology↗

bioRxiv2022

An Atlas of Cells in the Human Tonsil

Palatine tonsils are secondary lymphoid organs representing the first line of immunological defense against inhaled or ingested pathogens. Here, we present a comprehensive census of cell types forming the human tonsil by applying single-cell transcriptome, epigenome, proteome and adaptive immune repertoire sequencing as well as spatial transcriptomics, resulting in an atlas of >357,000 cells. We provide a glossary of 121 annotated cell types and states, and disentangle gene regulatory mechanisms that drive cells through specialized lineage trajectories. Exemplarily, we stratify multiple tonsil-resident myeloid slancyte subtypes, establish a distant BCL6 superenhancer as locally active in both follicle-associated T and B cells, and describe SIX5 as a potentially novel transcriptional regulator of plasma cell maturation. Further, our atlas is a reference map to understand alterations observed in disease. Here, we discover immune-phenotype plasticity in tumoral cells and microenvironment shifts of mantle cell lymphomas (MCL). To facilitate such reference-based analysis, we develop HCATonsilData and SLOcatoR, a computational framework that provides programmatic and modular access to our dataset; and allows the straightforward annotation of future single-cell profiles from secondary lymphoid organs.

immunology↗