Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

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PROS1 released by lung basal cells limits inflammation in epithelial and monocytes during SARS-CoV-2 infection

ABSTRACT: The data here represent two Single-Cell experiments performed to understand the roles of PROS1 in bronchial epithelial cells and monocytes, infected by SARS-CoV-2. The CVR EXP5 contains epithelial cultures grown on Air-Liquid Interface as mock or infected by the delta variant of SARS-CoV-2 (Delta B.1.617.2), and cocultures of mock or infected epithelium with CD14 monocytes. Some of these cultures were also supplemented with PROS1, to study the effects of the protein during infection. The CVR EXP1 contains cultures of PBMCs cultured in presence of SARS-CoV-2 variant (BetaCoV/England/02/2020/EPI_ISL_407073 ), with or without PROS1 supplementation. CVR EXP5 libraries were prepared using the Whole transcriptome Analysis and Sample Tag library Preparation kit (BD 633801), as per manufacture’s protocol (2019 version). CVR EXP1 libraries of 399 genes were prepared using BD Rhapsody Targeted mRNA and the Tag Amplification Kit (no. 633774) and primers from the BD Rhapsody Immune response Panel Hs (399 genes, BD 633750), as per manufacture’s protocol.

INSTRUMENT(S): NextSeq 500

ORGANISM(S): Homo sapiens

SUBMITTER: Theodoros Simakou

PROVIDER: E-MTAB-14405 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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PROS1 released by lung basal cells limits inflammation in epithelial and monocytes during SARS-CoV-2 infection.

Simakou Theodoros T Szemiel Agnieszka M AM MacDonald Lucy L Kerr Karen K Somma Domenico D Diallo Katy K Frew Jack J Hardy Olympia M OM Doohan Marcus M Elmesmari Aziza A McSharry Charles C Alivernini Stefano S Otto Thomas D TD Patel Arvind H AH Kurowska-Stolarska Mariola M

Discovery immunology 20250827 1

<h4>Introduction</h4>Factors regulating the severity of pneumonitis during viral infections remain unresolved. We previously found higher expression of protein S (PROS1) in lung epithelium of mild compared to severe coronavirus disease 2019 (COVID-19) patients. We hypothesized that PROS1 may protect the upper airways by regulating epithelial and myeloid cell responses during severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection.<h4>Methods</h4>To test this, <i>in vitro</i> air-l ...[more]

PMID: 40980495

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Project description:We employed CITE-Seq profiling of 62 277 high-quality FACS-enriched human bone marrow hematopoietic stem and progenitor cells (HSPCs) from 15 healthy donors representing young, mid and old age groups, using the BD Rhapsody platform. Our targeted gene panel consisting of 596 genes was supplemented with 46 cell-surface proteins to cover the most relevant markers of early HSPC differentiation and cell cycle status. We demonstrate a molecular map of early human hematopoietic stem cell (HSC) differentiation and provide evidence of early branching points into lineage trajectories across different age groups. Our data shows that the HSC branched into two main lineages, with the first branching point giving rise to megakaryocytic and erythroid progenitors (MKP/ERP), followed by lymphoid and myeloid progenitors (LMP/MDP). As expected, the most immature HSCs were defined by high expression of CD34, CD90, CRHBP, HOPX, HLF, MLLT3. Re-clustering and trajectory analysis of the most immature HSPCs confirmed early lineage commitment, suggesting that an MKP/ERP development does not include myeloid or lymphoid progenitors. A similar pattern was observed for all age groups. Interestingly, we observed increased expression of novel marker genes (HLA-E, DLK1, ADGRG6, and MMRN1) and the surface protein CD273/PD-L2 in the most immature HSCs. Besides a gradual upregulation of CD38 along differentiation, differentiated cells showed lower CD45 levels. tradeSeq analysis defined the continuous single cell expression changes in genes upon early differentiation and lineage commitment, allowing the detection of decision-making gene networks. Our data adds further evidence to a structured hierarchical organization of human hematopoiesis with a sequential loss of lineage potential, with the first branching point into the MEK/ERY lineage, and not an early commitment of uni-lineage restricted precursors. We report on the upregulation of ADGRG6, DLK1, HLA-E, MMRN1 and CD273 in the most immature HSCs. Functional experiments confirmed that CD273+ HSCs displayed the most quiescent profile with a high stemness signature as well as the immune-modulatory function of CD273+ on HSPCs in regulating T cell activation and cytokine release.

Dataset Information

PROS1 released by lung basal cells limits inflammation in epithelial and monocytes during SARS-CoV-2 infection

Publications

PROS1 released by lung basal cells limits inflammation in epithelial and monocytes during SARS-CoV-2 infection.

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