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A comprehensive investigation of ovarian cancer (OC) progression at the single-cell level is crucial for enhancing our understanding of the disease, as well as for the development of better diagnoses and treatments. Here, over half a million single-cell transcriptome data were collected from 84 OC patients across all clinical stages. Through integrative analysis, we identified heterogeneous epithelial-immune-stromal cellular compartments and their interactions in the OC microenvironment. The epithelial cells displayed clinical subtype features with functional variance. A significant increase in distinct T cell subtypes was identified including Tregs and CD8+ exhausted T cells from stage IC2. Additionally, we discovered antigen-presenting cancer-associated fibroblasts (CAFs), with myofibroblastic CAFs (myCAFs) exhibiting enriched extracellular matrix (ECM) functionality linked to tumor progression at stage IC2. Furthermore, the NECTIN2-TIGIT ligand-receptor pair was identified to mediate T cells communicating with epithelial, fibroblast, endothelial, and other cell types. Knock-out of NECTIN2 using CRISPR/Cas9 inhibited ovarian cancer cell (SKOV3) proliferation, and increased T cell proliferation when co-cultured. These findings shed light on the cellular compartments and functional aspects of OC, providing insights into the molecular mechanisms underlying stage IC2 and potential therapeutic strategies for OC. A single-cell interaction study on ovarian cancer reveals heterogeneous epithelial-immune-stromal cellular compartments and their interactions in shaping the tumor microenvironment, especially through the NECTIN2-TIGIT interaction. [ABSTRACT FROM AUTHOR]

Preeclampsia is a multifactorial and heterogeneous complication of pregnancy. Here, we utilize single-cell RNA sequencing to dissect the involvement of circulating immune cells in preeclampsia. Our findings reveal downregulation of immune response in lymphocyte subsets in preeclampsia, such as reduction in natural killer cells and cytotoxic genes expression, and expansion of regulatory T cells. But the activation of naïve T cell and monocyte subsets, as well as increased MHC-II-mediated pathway in antigen-presenting cells were still observed in preeclampsia. Notably, we identified key monocyte subsets in preeclampsia, with significantly increased expression of angiogenesis pathways and pro-inflammatory S100 family genes in VCAN+ monocytes and IFN+ non-classical monocytes. Furthermore, four cell-type-specific machine-learning models have been developed to identify potential diagnostic indicators of preeclampsia. Collectively, our study demonstrates transcriptomic alternations of circulating immune cells and identifies immune components that could be involved in pathophysiology of preeclampsia. A study profiled transcriptomic characteristic of circulating immune cells in preeclampsia pregnancy by scRNA-seq, then develop cell-type-specific models to identify potential diagnostic indicators of preeclampsia by machine learning. [ABSTRACT FROM AUTHOR]

Background: During pregnancy, mother–child interactions trigger a variety of subtle changes in the maternal body, which may be reflected in the status of peripheral blood mononuclear cells (PBMCs). Although these cells are easy to access and monitor, a PBMC atlas for pregnant women has not yet been constructed. Methods: We applied single‐cell RNA sequencing (scRNA‐seq) to profile 198,356 PBMCs derived from 136 pregnant women (gestation weeks 6 to 40) and a control cohort. We also used scRNA‐seq data to establish a transcriptomic clock and thereby predicted the gestational age of normal pregnancy. Results: We identified reconfiguration of the peripheral immune cell phenotype during pregnancy, including interferon‐stimulated gene upregulation, activation of RNA splicing‐related pathways and immune activity of cell subpopulations. We also developed a cell‐type‐specific model to predict gestational age of normal pregnancy. Conclusions: We constructed a single‐cell atlas of PBMCs in pregnant women spanning the entire gestation period, which should help improve our understanding of PBMC composition turnover in pregnant women. [ABSTRACT FROM AUTHOR]

The availability of viral entry factors is a prerequisite for the cross-species transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Large-scale single-cell screening of animal cells could reveal the expression patterns of viral entry genes in different hosts. However, such exploration for SARS-CoV-2 remains limited. Here, we perform single-nucleus RNA sequencing for 11 non-model species, including pets (cat, dog, hamster, and lizard), livestock (goat and rabbit), poultry (duck and pigeon), and wildlife (pangolin, tiger, and deer), and investigated the co-expression of ACE2 and TMPRSS2. Furthermore, cross-species analysis of the lung cell atlas of the studied mammals, reptiles, and birds reveals core developmental programs, critical connectomes, and conserved regulatory circuits among these evolutionarily distant species. Overall, our work provides a compendium of gene expression profiles for non-model animals, which could be employed to identify potential SARS-CoV-2 target cells and putative zoonotic reservoirs. Here the authors report single-nucleus RNA sequencing for several anatomical locations in 11 species, including cat, dog, hamster, lizard, goat, rabbit, duck, pigeon, pangolin, tiger, and deer, highlighting coexpression of SARS-CoV-2 entry factors ACE2 and TMPRSS2. [ABSTRACT FROM AUTHOR]

Purpose: Critically ill COVID-19 patients have significantly increased risk of death. Although several circulating biomarkers are thought to be related to COVID-19 severity, few studies have focused on the characteristics of critically ill patients with different outcomes. The objective of this study was to perform a longitudinal investigation of the potential mechanisms affecting the prognosis of critically ill COVID-19 patients. Methods: In addition to clinical data, 113 whole blood samples and 85 serum samples were collected from 33 severe and critical COVID-19 patients without selected comorbidities. Multi-omics analysis was then performed using longitudinal samples. Results: Obvious transcriptional transitions were more frequent in critical survivors than in critical non-survivors, indicating that phase transition may be related to survival. Based on analysis of differentially expressed genes during transition, the erythrocyte differentiation pathway was significantly enriched. Furthermore, clinical data indicated that red blood cell counts showed greater fluctuation in survivors than in non-survivors. Moreover, declining red blood cell counts and hemoglobin levels were validated as prognostic markers of poor outcome in an independent cohort of 114 critical COVID-19 patients. Protein–metabolite–lipid network analysis indicated that tryptophan metabolism and melatonin may contribute to molecular transitions in critical COVID-19 patients with different outcomes. Conclusions: This study systematically and comprehensively depicted the longitudinal hallmarks of critical COVID-19 patients and indicated that multi-omics transition may impact the prognosis. Take home message: Frequent transcriptional phase transitions may contribute to outcome in critically ill COVID-19 patients. Furthermore, fluctuation in red blood cell and hemoglobin levels may relate to poor prognosis. The biological function of melatonin was suppressed in COVID-19 non-survivors, which may provide a potential theoretical basis for clinical administration. [ABSTRACT FROM AUTHOR]

Vertebrate evolution was accompanied by two rounds of whole-genome duplication followed by functional divergence in terms of regulatory circuits and gene expression patterns. As a basal and slow-evolving chordate species, amphioxus is an ideal paradigm for exploring the origin and evolution of vertebrates. Single-cell sequencing has been widely used to construct the developmental cell atlas of several representative species of vertebrates (human, mouse, zebrafish, and frog) and tunicates (sea squirts). Here, we perform single-nucleus RNA sequencing (snRNA-seq) and single-cell assay for transposase accessible chromatin sequencing (scATAC-seq) for different stages of amphioxus (covering embryogenesis and adult tissues). With the datasets generated, we constructed a developmental tree for amphioxus cell fate commitment and lineage specification and characterize the underlying key regulators and genetic regulatory networks. The data are publicly available on the online platform AmphioxusAtlas. [Display omitted] • A snRNA-seq atlas of amphioxus developmental embryos and multiple adult tissues • A scATAC-seq atlas of amphioxus developmental embryos • A developmental tree for amphioxus cell fate commitment and lineage specification • Computational identification and validation of lineage-specific markers Ma et al. conduct a joint profiling of gene expression and chromatin accessibility during amphioxus embryogenesis at single-cell resolution. With the datasets generated, a developmental tree for amphioxus cell fate commitment and lineage specification is constructed, and multiple markers for each lineage are identified and validated. [ABSTRACT FROM AUTHOR]