Bulk and single-cell gene expression analyses reveal aging human choriocapillaris has pro-inflammatory phenotype

Voigt, Andrew P.; Whitmore, S. Scott; Mulfaul, Kelly; Chirco, Kathleen R.; Giacalone, Joseph C.; Flamme-Wiese, Miles J.; Stockman, Adam; Stone, Edwin M.; Tucker, Budd A.; Scheetz, Todd E.; Mullins, Robert F.

doi:10.1016/j.mvr.2020.104031

Cited by 40 publications

(31 citation statements)

References 57 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This project can provide the link between the known human DNA code and the individual cells that are responsible for function. Within the eye, single cell RNA sequencing has already been used to great effect in the study of the human retina (133), trabecular meshwork and uveoscleral aqueous outflow route (134, 135) and corneal limbus (136), but of the uveal tract only the choroid (in conjunction with the RPE) has so far been examined in this way (104,107). Voigt et al show a number of cell clusters within the combined RPE/choroid analysis, including the interesting finding of T-cells which need to be further defined.…”

Section: Discussionmentioning

confidence: 99%

“…Work applying single cell transcriptomics to the human choriocapillaris also suggests age dependent changes in the transcriptome of endothelial cells. For instance, endothelial cells from older donors exhibit enriched gene expression in pathways associated with trans-endothelial leukocyte migration compared to tissue from younger individuals, with the caveat that some of the tissue from the older donor cohort came from patients with changes consistent with age related macular degeneration (107).…”

Section: Choroidmentioning

confidence: 99%

See 1 more Smart Citation

The Cellular Composition of the Uveal Immune Environment

et al. 2021

View full text Add to dashboard Cite

The uveal tract consists of the iris, the ciliary body and the choroid; these three distinct tissues form a continuous layer within the eye. Uveitis refers to inflammation of any region of the uveal tract. Despite being grouped together anatomically, the iris, ciliary body and choroid are distinct functionally, and inflammatory diseases may affect only one part and not the others. Cellular structure of tissues direct their function, and understanding the cellular basis of the immune environment of a tissue in health, the “steady state” on which the perturbations of disease are superimposed, is vital to understanding the pathogenesis of those diseases. A contemporary understanding of the immune system accepts that haematopoietic and yolk sac derived leukocytes, though vital, are not the only players of importance. An array of stromal cells, connective tissue cells such as fibroblasts and endothelial cells, may also have a role in the inflammatory reaction seen in several immune-mediated diseases. In this review we summarise what is known about the cellular composition of the uveal tract and the roles these disparate cell types have to play in immune homeostasis. We also discuss some unanswered questions surrounding the constituents of the resident leukocyte population of the different uveal tissues, and we look ahead to the new understanding that modern investigative techniques such as single cell transcriptomics, multi-omic data integration and highly-multiplexed imaging techniques may bring to the study of the uvea and uveitis, as they already have to other immune mediated inflammatory diseases.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Choroidmentioning

confidence: 99%

The Cellular Composition of the Uveal Immune Environment

et al. 2021

View full text Add to dashboard Cite

show abstract

“…Human single cell transcriptome data from the scEiaD resource at plae.nei.nih.gov was searched for machine predicted RPE cells from fovea or peripheral punches. We found 217 cells, 159 from the fovea and 58 from the periphery, across four studies [26][27][28][29][30]. The Seurat object was downloaded on 2022-01-14 from plae.nei.nih.gov and subsetted to these 217 cells.…”

Section: Rna Extractionmentioning

confidence: 99%

Transcriptional mapping of the macaque retina and RPE-choroid reveals conserved inter-tissue transcription drivers and signaling pathways

Mungales

McGaughey

Zhang

et al. 2022

Preprint

View full text Add to dashboard Cite

Purpose: The macula and fovea comprise a highly sensitive visual detection tissue that is susceptible to common disease processes like age-related macular degeneration (AMD). Our understanding of the molecular determinants of high acuity vision remains unclear, as few model organisms possess a human-like fovea. We explore transcription factor networks and receptor-ligand interactions to elucidate tissue interactions in the macula and peripheral retina and concomitant changes in the underlying retinal pigment epithelium (RPE)/choroid. Methods: Poly-A selected, 100 bp paired-end RNA-sequencing (RNA-seq) was performed across the macular/foveal, perimacular, and temporal peripheral regions of the neural retina and RPE/choroid tissues of four adult Rhesus macaque eyes to characterize region- and tissue-specific gene expression. RNA-seq reads were mapped to both the macaque and human genomes for maximum alignment and analyzed for differential expression and Gene Ontology (GO) enrichment. Results: Comparison of the neural retina and RPE/choroid tissues indicated distinct, contiguously changing gene expression profiles from fovea through perimacula to periphery. Top GO enrichment of differentially expressed genes in the RPE/choroid included cell junction organization and epithelial cell development. Expression of transcriptional regulators and various disease-associated genes show distinct location-specific preference and retina-RPE/choroid tissue-tissue interactions. Conclusions: Regional gene expression changes in the macaque retina and RPE/choroid is greater than that found in previously published transcriptome analysis of the human retina and RPE/choroid. Further, conservation of human macula-specific transcription factor profiles and gene expression in macaque tissues suggest a conservation of programs required for retina and RPE/choroid function and disease susceptibility.

show abstract

“…Among the changes in cellular composition detected in endometriosis, we found endothelial cells (EC) to be markedly increased in peritoneal lesions, suggesting a possible role for angiogenesis. We identified components of the vascular system: four mural and seven endothelial cell subpopulations, according to careful analysis of previously described marker gene expression 5,6,[8][9][10] (Fig. 2a-c).…”

Section: Active Vascular Remodeling and Immune Cell-trafficking Prevail In Endometriosis Peritoneal Lesionsmentioning

confidence: 99%

Single cell analysis of endometriosis reveals a coordinated transcriptional program driving immunotolerance and angiogenesis across eutopic and ectopic tissues

Tan

Flynn

Sivajothi

et al. 2021

Preprint

View full text Add to dashboard Cite

Endometriosis is characterized by growth of endometrial-like tissue outside of the uterus affecting many women in their reproductive age, causing years of pelvic pain and potential infertility. Its pathophysiology remains largely unknown, limiting diagnosis and treatment. We characterized peritoneal and ovarian lesions at single-cell transcriptome resolution and compared to matched eutopic endometrium, control endometrium, and organoids derived from these tissues, generating data on over 100,000 cells across 12 individuals. We spatially localized many of the cell types using imaging mass cytometry. We identify a perivascular mural cell unique to the peritoneal lesions with dual roles in angiogenesis promotion and immune cell trafficking. We define an immunotolerant peritoneal niche, fundamental differences in eutopic endometrium and between lesions microenvironments, and a novel progenitor-like epithelial cell subpopulation. Altogether, this study provides a holistic view of the endometriosis microenvironment representing the first comprehensive cell atlas of the disease, essential information for advancing therapeutics and diagnostics.

show abstract

Bulk and single-cell gene expression analyses reveal aging human choriocapillaris has pro-inflammatory phenotype

Cited by 40 publications

References 57 publications

The Cellular Composition of the Uveal Immune Environment

The Cellular Composition of the Uveal Immune Environment

Transcriptional mapping of the macaque retina and RPE-choroid reveals conserved inter-tissue transcription drivers and signaling pathways

Single cell analysis of endometriosis reveals a coordinated transcriptional program driving immunotolerance and angiogenesis across eutopic and ectopic tissues

Contact Info

Product

Resources

About