PERICYTE-LIKE CELLS UNDERGO TRANSCRIPTIONAL REPROGRAMMING AND DISTINCT FUNCTIONAL ADAPTATIONS IN ACUTE LUNG INJURY
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ABSTRACT:
PROVIDER: PRJNA565238 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR10107700_1.fastq.gz | Fastqsanger.gz | |||
| SRR10107700_2.fastq.gz | Fastqsanger.gz | |||
| SRR10107701_1.fastq.gz | Fastqsanger.gz | |||
| SRR10107701_2.fastq.gz | Fastqsanger.gz | |||
| SRR10107702_1.fastq.gz | Fastqsanger.gz |
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Project description:Background: We previously reported on the role of pericyte-like cells as functional sentinel immune cells in lung injury. However, much about the biology of pericytes in lung injury remains unknown. Lung pericyte-like cells are well-positioned to sense disruption to the epithelial barrier and coordinate local inflammatory responses due to their anatomic niche within the alveoli. In this report, we characterized transcriptional responses and functional changes in pericyte-like cells following activation by alveolar components from injured and uninjured lungs. Methods: We purified pericyte-like cells from lung digests using PDGFR_ as a selection marker and expanded them in culture as previously described (1). We induced sterile acute lung injury in mice with recombinant human Fas ligand (rhFasL) instillation followed by mechanical ventilation (1). We then collected bronchoalveolar lavage fluid (BALF) from injured and uninjured mice. Purified pericyte-like cells in culture were exposed to growth media only (control), BALF from uninjured mice, and BALF from injured mice for 6 and 24 h. RNA collected from pericyte-like cells for each of these treatment conditions underwent genome-wide sequencing using RNA-seq. Targets of interest identified by bioinformatics analysis of RNA-seq data were validated using in vitro and in vivo assays. Results: We observed robust global transcriptional changes in pericyte-like cells following treatment with uninjured and injured BALF at 6 h, but this response persisted for 24 h only after exposure to injured BALF. Functional enrichment analysis of pericytes treated with injured BALF revealed activation of immuno-inflammatory, cell migration and angiogenesis-related pathways, whereas processes associated with tissue development and remodeling were down-regulated. We validated select targets in the inflammatory, angiogenesis-related, and cell migratory pathways using functional assays in vitro and in vivo. Conclusion: Lung pericyte-like cells are highly responsive to alveolar compartment content from both uninjured and injured lungs, but injured BALF elicits a more sustained response. The inflammatory, angiogenic, and migratory changes exhibited by activated pericyte-like cells underscore the phenotypic plasticity of these specialized stromal cells in the setting of acute lung injury.
2020-10-31 | GSE137363 | GEO
Project description:We previously reported on the role of pericyte-like cells as functional sentinel immune cells in lung injury. However, much about the biological role of pericytes in lung injury remains unknown. Lung pericyte-like cells are well-positioned to sense disruption to the epithelial barrier and coordinate local inflammatory responses due to their anatomic niche within the alveoli. In this report, we characterized transcriptional responses and functional changes in pericyte-like cells following activation by alveolar components from injured and uninjured lungs in a mouse model of acute lung injury (ALI). Purified pericyte-like cells from lung digests using PDGFRβ as a selection marker were expanded in culture as previously described (1). We induced sterile acute lung injury in mice with recombinant human Fas ligand (rhFasL) instillation followed by mechanical ventilation (1). We then collected bronchoalveolar lavage fluid (BALF) from injured and uninjured mice. Purified pericyte-like cells in culture were exposed to growth media only (control), BALF from uninjured mice, and BALF from injured mice for 6 and 24 hours. RNA collected from these treatment conditions were processed for RNAseq. Targets of interest identified by pathway analysis were validated using in vitro and in vivo assays. We observed robust global transcriptional changes in pericyte-like cells following treatment with uninjured and injured BALF at 6 hours, but this response persisted for 24 hours only after exposure to injured BALF. Functional enrichment analysis of pericytes treated with injured BALF revealed the activation of pro-inflammatory, cell migration, and angiogenesis-related pathways, whereas processes associated with tissue development and cell differentiation were down-regulated. We validated select upregulated targets in the inflammatory, angiogenic, and cell migratory pathways using functional biological assays in vitro and in vivo. We conclude that lung pericyte-like cells are highly responsive to alveolar compartment content from both uninjured and injured lungs, but injured BALF elicits a more sustained response. The inflammatory, angiogenic, and migratory changes exhibited by activated pericyte-like cells underscore the phenotypic plasticity of these specialized stromal cells in the setting of acute lung injury.
| S-EPMC10115144 | biostudies-literature
Project description:Increasing evidence shows that brain pericytes can acquire multipotency to produce multi-lineage cells following injury. However, pericytes are a heterogenous population and it remains unknown whether there are different potencies from different subsets of pericytes in response to injury. Here, using single-cell RNA-sequencing (scRNA-seq) and immunohistochemistry analysis following ischemic stroke, we showed that NG2+ pericyte subset expressed very strong neural reprogramming potential to produce newborn neurons, while Tbx18+ pericytes displayed strong multipotency to produce endothelial cells, fibroblasts, and microglia but with minimal neural reprogramming potency. In addition, we mimicked ischemic stroke in vitro and developed an NG2+ pericyte neural reprogramming culture model. Here we discovered that AMP-dependent kinase (AMPK) modulators facilitated pericyte to neuron conversion by modulating Ser436 phosphorylation status of CREB-binding protein (Cbp), a histone acetyltransferase, which coordinated an acetylation shift between the non-histone substrate (Sox2) and the histone substrate (H2B) and modulated Sox2 nuclear-cytoplasmic trafficking during reprogramming/differentiation process. Finally, we identified that sequential treatment of compound C (CpdC) and metformin, AMPK inhibitor and activator respectively through reprogramming/differentiation process, robustly facilitated the conversion of human pericyte into functional neurons via transient pericyte-derived neural stem cell population.
2024-10-01 | GSE250597 | GEO
Project description:A subpopulation of pericytes expressing the Glast-CreERT2 transgene (Type A pericytes) has recently been identified as the main source of stromal scar tissue that forms after SCI. Identification of molecules associated with pericyte-derived scarring may offer new therapeutic targets to facilitate axon regeneration following central nervous system (CNS) injury. We conducted genome-wide RNA sequencing of (i) uninjured spinal cord segments and (ii) lesion sites presenting full or attenuated pericyte-derived scarring 14 days after SCI.
2018-02-27 | GSE93976 | GEO
Project description:Background: Pericytes regulate vessel stabilization and function and their loss is associated with diseases such as diabetic retinopathy or cancer. Despite their physiological importance, pericyte function and molecular regulation during angiogenesis remain poorly understood. Methods: To decipher the transcriptomic programs of pericytes during angiogenesis, we crossed the Pdgfrb(BAC)-CreERT2 into the RiboTagflox/flox mice. Pericyte morphological changes were assessed in mural cell-specific R26-mTmG reporter mice, in which low doses of tamoxifen allowed labeling of single cell pericytes at high resolution. To study the role of phosphoinositide 3-kinase (PI3K) signaling in pericyte biology during angiogenesis, we used genetic mouse models which allow selective inactivation of PI3Kα and PI3Kβ isoforms and their negative regulator PTEN (phosphate and tensin homologue deleted on chromosome ten, PTEN) in mural cells. Results: At the onset of angiogenesis, pericytes exhibit molecular traits of cell proliferation and activated PI3K signaling, whereas during vascular remodeling pericytes upregulate genes involved in mature pericyte cell function, together with a remarkable decrease in PI3K signaling. Immature pericytes showed stellate shape and high proliferation, and mature pericytes were quiescent and elongated. Unexpectedly, we demonstrate that the PI3Kβ, but not PI3Kα, regulates pericyte proliferation and maturation during vessel formation. Genetic PI3Kβ inactivation in pericytes triggered early pericyte maturation. Conversely, unleashing PI3K signaling by means of PTEN deletion delayed pericyte maturation. Pericyte maturation was necessary to undergo vessel remodeling during angiogenesis. Conclusions: Our results identify new molecular and morphological traits associated to pericyte maturation and uncover PI3Kβ activity as a checkpoint to ensure appropriate vessel formation. In turn, our results may open new therapeutic opportunities to regulate angiogenesis in pathological processes through the manipulation of pericyte PI3Kβ activity.
2020-06-03 | GSE131534 | GEO
Project description:Primary somatosensory neurons specialize in transmitting distinct types of sensory information through differences in cell size, myelination, and the expression of various receptors and ion channels, which together define their transcriptional and functional identity. By profiling sensory ganglia at single-cell resolution, we find that the different somatosensory neuronal subtypes undergo a similar transcriptional response to peripheral nerve injury that both promotes axonal regeneration and suppresses cell identity. This transcriptional reprogramming, which is not observed in non-neuronal cells from sensory ganglia, resolves over a similar time course as target reinnervation and is associated with the restoration of original cell identity. Injury-induced transcriptional reprogramming requires ATF3, a transcription factor which is induced rapidly after injury and necessary for axonal regeneration and functional recovery. Our findings suggest that the transcription factors induced early after peripheral sensory neuron injury promote their transcriptional and functional metamorphosis, analogous to their known roles in reprogramming cell fate.
2020-07-22 | GSE154659 | GEO
Project description:Proteomics analysis can reveal the differences of protein expression between mural cells (known as pericytes) from normal adjacent tissues (NPC) and tumors (TPC), implying the effectiveness of pericyte to tumor.
2021-08-24 | PXD026963 | Pride
Project description:Adult stem cells undergo circadian reprogramming during ageing
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Project description:NG2+ and Tbx18+ pericyte subtypes exhibit distinct reprogramming potency following ischemic stroke
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Project description:Toll-like receptor (TLR) agonists induce metabolic reprogramming, which is required for immune activation. We have investigated mechanisms that regulate metabolic adaptation upon TLR-stimulation in human blood DC subsets, CD1c+ myeloid DCs (mDCs) and plasmacytoid DCs (pDCs). We show that TLR-stimulation changes expression of genes regulating oxidative phosphorylation (OXPHOS) and glutamine metabolism in pDC. TLR-stimulation increases mitochondrial content and intracellular glutamine in an autophagy-dependent manner in pDC. TLR-induced glutaminolysis fuels OXPHOS in pDCs. Notably, inhibition of glutaminolysis and OXPHOS prevents pDC activation. Conversely, TLR-stimulation reduces mitochondrial content, OXPHOS activity and induces glycolysis in CD1c+ mDC. Inhibition of mitochondrial fragmentation or promotion of mitochondrial fusion impairs TLR-stimulation induced glycolysis and activation of CD1c+ mDCs. TLR-stimulation triggers BNIP3-dependent mitophagy, which regulates transcriptional activity of AMPKα1. BNIP3-dependent mitophagy is required for induction of glycolysis and activation of CD1c+ mDCs. Our findings reveal that TLR stimulation differentially regulates mitochondrial dynamics in distinct human DC subsets, which contributes to their activation.
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