Single-Cell RNA Sequencing Reveals Novel Genes Regulated by Hypoxia in the Lung Vasculature

Thomas, Shelby; Manivannan, Sathiyanarayanan; Garg, Vidu; Lilly, Brenda

doi:10.1159/000522340

Cited by 8 publications

(5 citation statements)

References 52 publications

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“…ECs were analyzed as one cluster in this study. Similarly, a lung scRNAseq study by Thomas et al [6] in the chronic hypoxic mouse model (4-week hypoxia; n = 1/group) also analyzed ECs as one cluster in which they identified a migratory and proliferative phenotype in response to hypoxia, consistent with prior observations. However, a challenge of analyzing lung ECs in scRNAseq is to subcluster ECs into those that originate from arteries, veins, or capillaries from either the pulmonary or systemic circulation.…”

Section: Endothelial Cells (Artery)supporting

confidence: 77%

Charting the cellular landscape of pulmonary arterial hypertension through single-cell omics

Tang,

Vadgama,

Redmann

et al. 2024

Respir Res

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This review examines how single-cell omics technologies, particularly single-cell RNA sequencing (scRNAseq), enhance our understanding of pulmonary arterial hypertension (PAH). PAH is a multifaceted disorder marked by pulmonary vascular remodeling, leading to high morbidity and mortality. The cellular pathobiology of this heterogeneous disease, involving various vascular and non-vascular cell types, is not fully understood. Traditional PAH studies have struggled to resolve the complexity of pathogenic cell populations. scRNAseq offers a refined perspective by detailing cellular diversity within PAH, identifying unique cell subsets, gene networks, and molecular pathways that drive the disease. We discuss significant findings from recent literature, summarizing how scRNAseq has shifted our understanding of PAH in human, rat, and mouse models. This review highlights the insights gained into cellular phenotypes, gene expression patterns, and novel molecular targets, and contemplates the challenges and prospective paths for research. We propose ways in which single-cell omics could inform future research and translational efforts to combat PAH.

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Section: Endothelial Cells (Artery)supporting

confidence: 77%

Charting the cellular landscape of pulmonary arterial hypertension through single-cell omics

Tang,

Vadgama,

Redmann

et al. 2024

Respir Res

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“…Single-cell suspension was achieved by enzymatically dissociation and depletion of CD45 + CD326+ cells after Miltenyi AUTOMACS sorting. To better resolve differences between heterogeneity of cells using unsupervised graph clustering partitioned cells into groups, we combined a published data set of hypoxic and normxic lung cells with ours (Thomas et al, 2022 ; Data ref: Lilly et al, 2022 ) and visualized all of them using uniform manifold approximation and projection (UMAP; Fig. 3A ).…”

Section: Resultsmentioning

confidence: 99%

Pericytes contribute to pulmonary vascular remodeling via HIF2α signaling

Kim,

Liu,

Kim

et al. 2024

EMBO Rep

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Vascular remodeling is the process of structural alteration and cell rearrangement of blood vessels in response to injury and is the cause of many of the world’s most afflicted cardiovascular conditions, including pulmonary arterial hypertension (PAH). Many studies have focused on the effects of vascular endothelial cells and smooth muscle cells (SMCs) during vascular remodeling, but pericytes, an indispensable cell population residing largely in capillaries, are ignored in this maladaptive process. Here, we report that hypoxia-inducible factor 2α (HIF2α) expression is increased in the lung tissues of PAH patients, and HIF2α overexpressed pericytes result in greater contractility and an impaired endothelial-pericyte interaction. Using single-cell RNAseq and hypoxia-induced pulmonary hypertension (PH) models, we show that HIF2α is a major molecular regulator for the transformation of pericytes into SMC-like cells. Pericyte-selective HIF2α overexpression in mice exacerbates PH and right ventricular hypertrophy. Temporal cellular lineage tracing shows that HIF2α overexpressing reporter NG2+ cells (pericyte-selective) relocate from capillaries to arterioles and co-express SMA. This novel insight into the crucial role of NG2+ pericytes in pulmonary vascular remodeling via HIF2α signaling suggests a potential drug target for PH.

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“…Hence, we chose two typical conditions of hypoxia exposure, T_30 and T_60, to understand well the temporal switching of hypoxia-inducible genes. They investigated the role of Notch 3 genes by employing single-cell RNA sequencing to compare lung cells of wild-type (Wt) mice exposed to 28 days of hypoxia against those of control mice in normoxic conditions [33]. Additionally, hypoxia, a hallmark of cancers, was examined using single-cell sequencing in a study by Yanru Zhang.…”

Section: Discussionmentioning

confidence: 99%

Single Cell sequencing reveals heterogenicity of differential gene-expression and altered interactome in post ischemic mice brain cells

Lu,

Hou,

Wang

et al. 2024

Arch Med Sci

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IntroductionIschemia, resulting from reduced blood supply due to arterial constriction or blockages, leads to oxygen and nutrient deprivation, impacting various body systems and contributing to numerous diseases. Despite extensive research on ischemia, molecular studies with spatial and temporal specificity are limited. Our study utilized single-cell genomics to investigate hypoxia-induced changes in the mouse brain at 30 and 60 minutes of exposure, aiming to map cellular trajectories, ontologies, and expression patterns in a cell-specific manner.Material and methodsWe developed a mouse model of hypoxia using the thread-plug method. Experimental groups were exposed to hypoxia for 30 minutes (T_30) and 60 minutes (T_60), with a sham surgery group as control. After excising the cerebral cortex, we performed nuclear isolation and library construction for spatio-temporal analysis of cortical cells. Data analysis included differential gene expression, trajectory analysis, examination of gene regulatory networks, and hallmark analysis.ResultsSingle-cell genomics analysis revealed 12 distinct cell populations with different transcriptomic profiles. Spatio-temporal distinctions in cell signaling were observed, showing a switch from Ras GTPase signaling to calmodulin and calcium-dependent signaling between the two hypoxia levels. In the T_30 group, distal axons and growth cones were transcriptionally active, while in the T_60 group, cell edges and post-synaptic areas were more active. The synaptic vesicle cycle was implicated in transcriptional changes across the T_30 and T_60 groups.ConclusionsOur single-cell genomics study provides new insights into cellular dynamics during hypoxia. The identified cell populations and molecular pathways highlight potential targets for further research and the development of targeted therapies for ischemia.

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Single-Cell RNA Sequencing Reveals Novel Genes Regulated by Hypoxia in the Lung Vasculature

Cited by 8 publications

References 52 publications

Charting the cellular landscape of pulmonary arterial hypertension through single-cell omics

Charting the cellular landscape of pulmonary arterial hypertension through single-cell omics

Pericytes contribute to pulmonary vascular remodeling via HIF2α signaling

Single Cell sequencing reveals heterogenicity of differential gene-expression and altered interactome in post ischemic mice brain cells

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