Screening and identification of muscle pericyte-selective markers
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ABSTRACT:
PROVIDER: PRJNA1290998 | ENA |
REPOSITORIES: ENA
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Project description:Pericytes, which share markers with smooth muscle cells (SMCs), are heterogenous cells. Pericytes in the brain and skeletal muscle have different embryonic origins, representing distinct subpopulations. One challenge in the field is that there are no subpopulation-specific pericyte markers. Here, we compared the transcriptomes of muscle pericytes and SMCs, and identified 741 muscle pericyte-enriched genes and 564 muscle SMC-enriched genes. Gene ontology analysis uncovered distinct biological processes and molecular functions in muscle pericytes and SMCs. Interestingly, the Venn diagram revealed only one gene shared by brain and muscle pericytes, suggesting that they are indeed distinct subpopulations with different transcriptional profiles. We further validated that GSN co-localized with PDGFRβ+SMA- cells in small and large blood vessels but not PDGFRβ+SMA+ cells, indicating that GSN predominantly marks pericytes and fibroblasts rather than SMCs in skeletal muscle. Negligible levels of GSN were detected in the brain. These findings indicate that GSN may serve as a selective marker for muscle pericytes.
2025-07-16 | GSE302448 | GEO
Project description:BackgroundPericytes, a type of mural cells, exert important functions in the CNS. One major challenge in pericyte research is the lack of pericyte-specific and subpopulation-specific markers.MethodsTo address this knowledge gap, we first generated a novel transgenic mouse line in which vascular smooth muscle cells (vSMCs) are permanently labeled with tdTomato. Next, we isolated PDGFRβ+tdTomato- pericytes and PDGFRβ+tdTomato+ vSMCs from the brains of these mice and subsequently performed RNAseq analysis to identify pericyte-enriched genes.ResultsUsing this approach, we successfully identified 40 pericyte-enriched genes and 158 vSMC-enriched genes, which are involved in different biological processes and molecular functions. Using ISH/IHC analysis, we found that Pla1a and Cox4i2 were predominantly enriched in subpopulations of brain pericytes, although they also marked some non-vascular parenchymal cells.ConclusionsThese findings suggest that Pla1a and Cox4i2 preferably label subpopulations of pericytes in the brain compared to vSMCs, and thus, they may be useful in distinguishing these populations.
| S-EPMC11799917 | biostudies-literature
Project description:Integrated molecular analysis identifies new developmental pericyte markers in zebrafish
| PRJNA734950 | ENA
Project description:Genomewide screening for pectoral fin MN specific markers
| PRJNA414974 | ENA
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:We performed single cell and bulk RNA-seq analyses on pdgfrb-positive cells to identify candidate pericyte-expressed genes. For bulk RNA-seq, we used wild type pdgfrb-positive samples from Series GSE152759 (GEO ID: GSM4625924, GSM4625925, GSM4625926) for comparison to mutant pdgfrb-positive cells in this Series. These cells had originally been isolated in parallel.
2021-11-10 | GSE176129 | GEO
Project description:Pericytes are intrinsic components of vessels that regulate vascular stability and permeability. Aberrant vascularization is a hallmark of cancer, although the contribution of pericytes to this process is poorly understood. Here, we undertook a combined computational and experimental strategy to identify the molecular reprogramming of prostate pericytes during cancer pathogenesis and progression. Analysis of human prostate cancer and murine mouse models showed that prostate tumors exhibit a disequilibrium between endothelial and pericyte content with prognostic potential. Deeper molecular analysis revealed that there is no overt loss of pericytes in prostate tumors, but rather a disfunction that is concomitant with altered expression of a subset of cellular markers. We translate this finding into a simplified signature that discriminates pericyte abundance versus function. Leveraging single-cell RNA sequencing data, we find that TGFβ governs the molecular changes that underlie pericyte disfunction in tumors. This mechanism is associated with reduced pericyte contractility, enlargement of vascular lumen and increased permeability in prostate cancer. Altogether, this study revisits the paradigm of reduced number of pericyte in favor of their disfunction in tumors, and the importance of paracrine signaling in this process.
2025-10-03 | GSE278801 | 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:Brain pericytes are one of the critical cell types that regulate endothelial barrier function and activity, thus ensuring adequate blood flow to the brain. The genetic pathways guiding undifferentiated cells into mature pericytes are not well understood. We show here that pericyte precursor populations from both neural crest and head mesoderm of zebrafish express the transcription factor nkx3.1 develop into brain pericytes. We identify the gene signature of these precursors and show that an nkx3.1-, foxf2a-, and cxcl12b-expressing pericyte precursor population is present around the basilar artery prior to artery formation and pericyte recruitment. The precursors later spread throughout the brain and differentiate to express canonical pericyte markers. Cxcl12b-Cxcr4 signaling is required for pericyte attachment and differentiation. Further, both nkx3.1 and cxcl12b are necessary and sufficient in regulating pericyte number as loss inhibits and gain increases pericyte number. Through genetic experiments, we have defined a precursor population for brain pericytes and identified genes critical for their differentiation. This SuperSeries is composed of the SubSeries listed below.
2024-02-25 | GSE232763 | GEO
Project description:The efficacy of T cell-based immunotherapies is limited by the immune-suppressive tumor environment mediated by hypoxia, arising from dysfunctional blood vessels. Normalizing the tumor vascular bed can translate into an immune-supportive microenvironment. Here, we show that targeting pericytes to achieve durable vessel normalization can improve immunotherapy outcomes. Specifically, we identified regulator of G protein signaling 5 (RGS5) as a master regulator of tumor pericyte differentiation. Loss of RGS5 function changes the tumor microenvironment by inducing pericyte quiescence and maturity via Rho kinase activation and expression of contractile proteins. The mature pericyte state affords highly sustained vascular changes, which profoundly facilitates anti-tumor immune activity. Importantly, we show that selective low dose therapeutics can induce pericyte maturity and contractility, which mimics genetic RGS5 loss in both mouse and human tumors. Low dose drug therapy durably changes the tumor microenvironment without inducing adaptive resistance, rendering malignant cells more sensitive to immunotherapies. Our findings create a new approach with highly translatable opportunities to improve the outcomes of immune combination therapies.
2024-08-23 | GSE271508 | GEO