Biology subjects

De Domenico, E.

Publications and source records attributed to De Domenico, E..

3 recordsLinked to original sources

bioRxiv2025

Molecular determinants of brain-resident CD8+ T cell formation and function

Tissue-resident memory T (Trm) cells are strategically located to provide frontline protection upon antigen re-encounter while possessing tissue-specific transcriptional programs. Whether brain Trm cells similarly adapt to their tissue environment, and to what extent their molecular signature is altered in neuropathology, remains unclear. Here we profile brain Trm cells under homeostasis and in the contexts of aging, beta-amyloidosis, and systemic viral infection. From these studies, a tissue-specific CD8+ T cell landscape emerged, defined by the expression of the transcription factor TCF-1 and the inhibitory receptor PD-1. TCF-1 was critical for the formation and phenotypic maturation of brain CD8+ Trm cells, while PD-1 signaling was necessary for robust effector function and antigen-specific recall response. In addition, the cytokine transforming growth factor (TGF)-{beta} was required for the differentiation of brain CD8+ Trm cells and restricted their transition into effector-like cells upon antigenic rechallenge. These findings highlight common as well as tissue-specific features of brain CD8+ Trm cells and provide insights into the molecular mechanisms governing their formation and function.

immunology↗

bioRxiv2024

Characterizing human CMV-specific CD8+ T cells using multi-layer single-cell omics

In this study we established a comprehensive workflow to collect multi-omics single-cell data using a commercially available micro-well based platform. This included whole transcriptome, cell surface markers (targeted sequencing-based cell surface proteomics), T cell specificities, adaptive immune receptor repertoire (AIRR) profiles and sample multiplexing. With this technique we identified novel paired T cell receptor sequences for three prominent human CMV epitopes. In addition, we review the ability of dCODE dextramers to detect antigen-specific T cells at low frequencies by estimating sensitivities and specificities when used as reagents for single-cell multi-omics. MotivationIn this study, we report the first five-layer multi-omics dataset using the BD Rhapsody single-cell platform for the characterization of human antigen-specific T cells. Modalities include whole transcriptome, T cell receptor (TCR) sequences, T cell antigen specificity measured by dCODE dextramers, surface marker proteins and combinatorial sample multiplexing combining two distinct hashing approaches.

genomics↗

bioRxiv2024

Dysregulation of gene expression during gastrulation results in impaired primitive erythropoiesis and vascular development in Trim71-KO embryos

The transition of an embryo from gastrulation to organogenesis requires precisely coordinated changes in gene expression. The RNA-binding protein Trim71 is essential for embryonic survival, but its exact role in mammalian development in vivo remains poorly defined. Here we show that murine Trim71-KO embryos appear normal until embryonic day (E)8.5 but display severe defects in primitive erythropoiesis, yolk sac vasculature and heart function during the onset of organogenesis at E9.5 and E10.5. This led to an impaired vascular translocation of yolk sac-derived macrophage progenitors to the embryo head, independent of Trim71 expression in erythro-myeloid progenitors. The cardiovascular and erythropoiesis defects explain the embryonic lethality upon global Trim71-KO. Targeting Trim71 in hematoendothelial progenitors did not induce strong developmental defects, indicating an earlier developmental origin of these phenotypes in Trim71-KO embryos. ScRNA-seq of E7.5 Trim71-KO embryos revealed that transcriptomic changes arise already at gastrulation, showing a strong upregulation of the transcription factor Eomes. We identify Eomes as a direct target of Trim71-mediated mRNA repression via the NHL domain, demonstrating a functional link of Trim71 to a key regulator of mesodermal development. Taken together, our data suggest that Trim71-dependent control of gene expression at gastrulation establishes a framework for proper development during organogenesis.

developmental biology↗