Single-Cell Characterization of the Frizzled 5 (Fz5) Mutant Mouse and Human Persistent Fetal Vasculature (PFV)
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ABSTRACT:
PROVIDER: PRJNA838602 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR19226234_1.fastq.gz | Fastqsanger.gz | |||
| SRR19226234_2.fastq.gz | Fastqsanger.gz | |||
| SRR19226235_1.fastq.gz | Fastqsanger.gz | |||
| SRR19226235_2.fastq.gz | Fastqsanger.gz | |||
| SRR19226236_1.fastq.gz | Fastqsanger.gz |
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Project description:During early development, a transitory fetal vasculature of the vitreous hyaloid vessels (HV) provides temporary nutrients for the developing lens and retina. HV regresses when the intraretinal vasculature develops to replace its function. Failure in regression of the HV leads to persistent fetal vasculature (PFV), a pathological condition accounting for 4.8% children blindness in the USA. To date, the HV formation and regression as well as the related PFV pathogenesis are largely unknown. In this study, by single-cell RNA sequencing (scRNA-seq) the vitreous cells derived from normal and the Fzd5 mutant mice at two time points, postnatal day 3 (P3) and P6, we collectively defined 10 major cell types, present in both wild type and mutant developing vitreous but with much higher numbers of endothelial cells, macrophages, erythroid-like cells, pericytes, smooth muscle cells, fibroblasts and melanocytes in the P3 mutants. Both mutant and wild type cell types declined to similar sizes at P6 with varied compositions of sub clusters. We further compared gene expression profiles of residual major sub clusters at P6, and showed altered metabolic activities of the mutant cells. Additionally, two macrophage clusters expressed markers for hyalocytes supporting the notion that these cells are of macrophage origin. The melanocytes predominantly existed in the Fzd5 mutants expressing neural crest markers including Pax3 and Sox10, similar to that of choroidal pigment cells. Taken together, these data revealed cell features of normal and pathological hyaloid tissues, which has not been known precedentially.
2023-05-31 | GSE203116 | GEO
Project description:PurposePersistent fetal vasculature (PFV) is a pathological condition accounting for 4.8% of children's blindness in the United States. However, the PFV cell composition and pathogenetic mechanisms are poorly understood. This study aims to characterize PFV cell composition and associated molecular features and attempts to lay a foundation for further understanding the disease.MethodsImmunohistochemistry was conducted to characterize cell types at the tissue level. Single-cell RNA sequencing (sc-RNAseq) was performed on the vitreous cells derived from normal and Fz5 mutant mice at two early postnatal ages and human PFV samples. Bioinformatic tools were used to cluster cells and analyze their molecular features and functions.ResultsThe findings of this study are as follows: (1) a total of 10 defined and one undefined cell types were characterized in both the hyaloid vessel system and PFV by sc-RNAseq and immunohistochemistry; (2) neural crest-derived melanocytes, astrocytes, and fibroblasts were specifically retained in the mutant PFV; (3) Fz5 mutants were found to possess more vitreous cells at early postnatal age 3 but returned to similar levels as the wild type at postnatal age 6; (4) altered phagocytic and proliferation environments and cell-cell interactions were detected in the mutant vitreous; (5) the human PFV samples shared fibroblast, endothelial and macrophage cell types with the mouse, but having distinct immune cells including T cells, NK cells and Neutrophils; and last, (6) some neural crest features were also shared between certain mouse and human vitreous cell types.ConclusionsWe characterized PFV cell composition and associated molecular features in the Fz5 mutant mice and two human PFV samples. The excessively migrated vitreous cells, intrinsic molecular properties of these cells, phagocytic environment, and cell-cell interactions may together contribute to PFV pathogenesis. Human PFV shares certain cell types and molecular features with the mouse.
| S-EPMC9988703 | biostudies-literature
Project description:ObjectiveTo analyse outcomes in different forms of persistent fetal vasculature (PFV).Methods and analysisRetrospective cohort study at a university-based practice of children presenting with PFV between 2011 and 2020. Exclusion criteria was surgical management outside of our institution and follow-up less than 1 month. Wilcoxon and Student's t-tests were used for statistical analysis.ResultsForty-six eyes of 45 patients presented with PFV at 16.7±31.3 (median 2.8) months old with 32.6±29.8 (median 22.5) months of follow-up. Types of PFV included: mild combined anterior-posterior (23 eyes, 50%), severe combined anterior-posterior (18 eyes, 39%), severe anterior (3 eyes, 7%), mild anterior (1 eye, 2%) and posterior (1 eye, 2%). Thirty-two eyes (70%) underwent PFV surgical correction; lensectomy (13 mild combined), vitrectomy (3 mild combined), sequential lensectomy then vitrectomy (3 severe combined), combined lensectomy-vitrectomy (11 severe anterior or severe combined), laser retinopexy (1 mild combined). Five eyes required additional vitrectomy surgery for retinal detachment, fold or cyclitic membrane. Nine eyes developed glaucoma, six requiring Intraocular pressure (IOP)-lowering surgery. At final follow-up, 32 eyes had at least form vision and 6 eyes were aversive to light. Eight eyes, all which were severe combined, and four that did not undergo PFV surgery, were unable to detect light due to phthisis bulbi (7) and optic nerve hypoplasia (1).ConclusionsClassification of PFV is important in determining surgical approach with severe cases often requiring both lensectomy and vitrectomy for optimal anatomic and functional outcomes.
| S-EPMC8094357 | biostudies-literature
Project description:PurposeTo describe the frequency, characteristics, and treatment outcome of persistent fetal vasculature (PFV) in children undergoing surgery for congenital and infantile cataract in the first 2 years of life.Patients and methodsObservational population-based cohort study with case identification through active surveillance and standardised data collection via a national clinical network, the British Isles Congenital Cataract Interest Group (BCCIG).ResultsThe IoLunder2 cohort comprises 246 children undergoing surgery for bilateral and unilateral congenital and infantile cataract in the first 2 years of life. A total of 58/246 (24%) children had PFV (%): overall, 46/95 (46%) with unilateral cataract, and 12/141 (8%) with bilateral disease. Anterior segment vascular remnants were more common in bilateral than unilateral disease (75 vs 11%, P=0.01). At 1 year after surgery, 20% of children with bilateral PFV and 24% with unilateral had achieved normal vision for age within the operated eye. The prevalence of post-operative glaucoma was 9% (of children with bilateral disease) and 4% (unilateral).ConclusionPFV is significantly more common than previously reported, and outcomes are comparable to that for congenital and infantile cataract overall.
| S-EPMC5023809 | biostudies-literature
Project description:An 11-month-old baby girl presented with white reflex in her left eye. On examination, there was a 6.5×5 mm(2)haemangioma present over her face involving on her lower lip. Systemic examinations were within normal limits. The left eye was small, with an axial length of 16.08 mm and had a cataract. Ultrasonography of the left eye was suggestive of the presence of a vascular stalk, persistent hyperplasia of a primary vitreous, or persistent fetal vasculature with vitreous haemorrhage. On MRI, the left eye was small with vitreous haemorrhage. Left eye lens aspiration was performed and the bleeding vascular stalk behind the lens was cauterised with diathermy. The right eye was normal. The patient was diagnosed as having PHACE syndrome (Posterior fossa malformations, Hemangiomas, Arterial anomalies, Coarctation of the aorta and other cardiac defects, and Eye abnormalities syndrome). On follow-up, she was able to follow light with her left eye.
| S-EPMC4840598 | biostudies-literature
Project description:Adult hematopoietic stem cells (HSCs) respond directly to inflammation and infection, resulting in both acute and persistent changes in quiescence, mobilization, and differentiation. Here we show that fetal HSCs respond to maternal inflammation in utero, and the fetal response drives long-term changes to postnatal hematopoiesis and immunity. Heterogeneous fetal hematopoietic stem and progenitor cells (HSPCs) show divergent responses to maternal immune activation (MIA), including changes in quiescence, expansion, and immune cell output. Single cell transcriptomic analysis of fetal HSPCs reveals specific upregulation of inflammation-responsive genes in discrete populations, in response to upregulated IFNα and IL-1α in the fetal liver cytokine milieu. Postnatally, MIA caused the inappropriate expansion and persistence of transient progenitors, concomitant with increased cellularity and hyper-responsiveness of fetal-derived immune cells. Our investigation demonstrates how inflammation in utero can direct the trajectory of hematopoiesis and immunity by reshaping fetal HSC establishment.
2023-01-27 | GSE161926 | GEO
Project description:Adult hematopoietic stem cells (HSCs) respond directly to inflammation and infection, resulting in both acute and persistent changes in quiescence, mobilization, and differentiation. Here we show that fetal HSCs respond to maternal inflammation in utero, and the fetal response drives long-term changes to postnatal hematopoiesis and immunity. Heterogeneous fetal hematopoietic stem and progenitor cells (HSPCs) show divergent responses to maternal immune activation (MIA), including changes in quiescence, expansion, and immune cell output. Single cell transcriptomic analysis of fetal HSPCs reveals specific upregulation of inflammation-responsive genes in discrete populations, in response to upregulated IFNα and IL-1α in the fetal liver cytokine milieu. Postnatally, MIA caused the inappropriate expansion and persistence of transient progenitors, concomitant with increased cellularity and hyper-responsiveness of fetal-derived immune cells. Our investigation demonstrates how inflammation in utero can direct the trajectory of hematopoiesis and immunity by reshaping fetal HSC establishment.
2023-01-27 | GSE161925 | GEO
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Project description:A broad range of brain pathologies critically relies on the vasculature, and cerebrovascular disease is a leading cause of death worldwide. However, the cellular and molecular architecture of the human brain vasculature remains incompletely understood. Here, we performed single-cell RNA sequencing of 606,380 freshly isolated endothelial, perivascular and other tissue-derived cells from 117 samples, from 68 human fetuses and adult patients to construct a molecular atlas of the developing fetal, adult control and diseased human brain vasculature. We uncover extensive molecular heterogeneity of the vasculature of healthy fetal and adult human brains and across eight vascular-dependent Central Nervous System (CNS) pathologies including brain tumors and brain vascular malformations. We identify alteration of arteriovenous differentiation and reactivated fetal as well as conserved dysregulated genes and pathways in the diseased vasculature. Pathological endothelial cells display a loss of CNS-specific properties and reveal an upregulation of MHC class II molecules, indicating atypical features of CNS endothelial cells. Cell-cell interaction analyses predict numerous endothelial-to-perivascular cell ligand-receptor crosstalk including immune-related and angiogenic pathways, thereby unraveling a central role for the endothelium within brain neurovascular unit signaling networks. Our single-cell brain atlas provides insight into the molecular architecture and heterogeneity of the developing, adult/control and diseased human brain vasculature and serves as a powerful reference for future studies
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Project description:A broad range of brain pathologies critically relies on the vasculature, and cerebrovascular disease is a leading cause of death worldwide. However, the cellular and molecular architecture of the human brain vasculature remains incompletely understood. Here, we performed single-cell RNA sequencing of 606,380 freshly isolated endothelial, perivascular and other tissue-derived cells from 117 samples, from 68 human fetuses and adult patients to construct a molecular atlas of the developing fetal, adult control and diseased human brain vasculature. We uncover extensive molecular heterogeneity of the vasculature of healthy fetal and adult human brains and across eight vascular-dependent Central Nervous System (CNS) pathologies including brain tumors and brain vascular malformations. We identify alteration of arteriovenous differentiation and reactivated fetal as well as conserved dysregulated genes and pathways in the diseased vasculature. Pathological endothelial cells display a loss of CNS-specific properties and reveal an upregulation of MHC class II molecules, indicating atypical features of CNS endothelial cells. Cell-cell interaction analyses predict numerous endothelial-to-perivascular cell ligand-receptor crosstalk including immune-related and angiogenic pathways, thereby unraveling a central role for the endothelium within brain neurovascular unit signaling networks. Our single-cell brain atlas provides insight into the molecular architecture and heterogeneity of the developing, adult/control and diseased human brain vasculature and serves as a powerful reference for future studies
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