Comprehensive phenotyping of endothelial cells using flow cytometry 2: Human

Grant, Dillon; Wanner, Nicholas; Frimel, Matthew; Erzurum, Serpil C.; Asosingh, Kewal

doi:10.1002/cyto.a.24293

Cited by 11 publications

(11 citation statements)

References 113 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…As a molecule responsible for initiating physiologic penile erection, NO catalyzed by endothelial nitric oxide synthase in the blood vessel appears essential for vasodilation of penile arteries via the NO-sGC-cGMP pathway ( 21 , 22 ). In our study, pan-endothelial cell markers and other canonical markers are used to identify ECs in the human corpus cavernosum ( 23 – 25 ). The proportion of ECs was largest in the patient with primary vasculogenic ED (P#1).…”

Section: Discussionmentioning

confidence: 99%

Single-Cell RNA Sequencing of Human Corpus Cavernosum Reveals Cellular Heterogeneity Landscapes in Erectile Dysfunction

et al. 2022

View full text Add to dashboard Cite

PurposeTo assess the diverse cell populations of human corpus cavernosum in patients with severe erectile dysfunction (ED) at the single-cell level.MethodsPenile tissues collected from three patients were subjected to single-cell RNA sequencing using the BD Rhapsody™ platform. Common bioinformatics tools were used to analyze cellular heterogeneity and gene expression profiles from generated raw data, including the packages Seurat, Monocle, and CellPhoneDB.ResultsDisease-related heterogeneity of cell types was determined in the cavernous tissue such as endothelial cells (ECs), smooth muscle cells, fibroblasts, and immune cells. Reclustering analysis of ECs identified an arteriole ECs subcluster and another one with gene signatures of fibroblasts. The proportion of fibroblasts was higher than the other cell populations and had the most significant cellular heterogeneity, in which a distinct subcluster co-expressed endothelial markers. The transition trajectory of differentiation from smooth muscle cells into fibroblasts was depicted using the pseudotime analysis, suggesting that the expansion of corpus cavernosum is possibly compromised as a result of fibrosis. Cell-cell communications among ECs, smooth muscle cells, fibroblasts, and macrophages were robust, which indicated that inflammation may also have a crucial role in the development of ED.ConclusionsOur study has demonstrated a comprehensive single-cell atlas of cellular components in human corpus cavernosum of ED, providing in-depth insights into the pathogenesis. Future research is warranted to explore disease-specific alterations for individualized treatment of ED.

show abstract

Section: Discussionmentioning

confidence: 99%

Single-Cell RNA Sequencing of Human Corpus Cavernosum Reveals Cellular Heterogeneity Landscapes in Erectile Dysfunction

et al. 2022

View full text Add to dashboard Cite

show abstract

“…The debate was somewhat attenuated after a multicenter observational study enrolling 323 patients verified a protocol gating alive and nucleated, CD34 bright /CD45 − /CD146 + cells as the more reliable phenotype for CEC selection ( 50 ), and indeed most studies that utilize flow cytometry to detect CECs from PBMCs do so by a common CD45 depletion step. However, the ongoing variety of protocols utilized in the field ( Table 1 ) argues for further elucidation on the best method to quantify CECs ( 52 , 53 ). An approach targeting the transcriptomic signature of these cells may allow for better insight into CEC identity and function while improving the specificity and sensitivity of CEC detection.…”

Section: Established Methods In Cec Research and The Argument For Tra...mentioning

confidence: 99%

Are circulating endothelial cells the next target for transcriptome-level pathway analysis in ARDS?

Monteiro

Matthay

2023

American Journal of Physiology-Lung Cellular and Molecular Phys

View full text Add to dashboard Cite

Acute Respiratory Distress Syndrome (ARDS) has had no mortality-improving pharmacological intervention despite 50 years of high-caliber research due to its heterogeneity.(1) For the field to advance, better definitions for ARDS subgroups that more uniformly respond to therapies are needed.(2-6) A plethora of high quality clinical research has uncovered the next generation of soluble biomarkers that provide the predictive enrichment necessary for trial recruitment, however plasma-soluble markers do not specify the damaged organ of origin nor do they provide insight into disease mechanisms. In this Perspective, we make the case for querying the transcriptome of circulating endothelial cells (CECs), which when shed from vessels after inflammatory insult, become heralds of site-specific inflammatory damage. We review the application of CEC quantification to multiple disease phenotypes (including myocardial infarction, vasculitides, cancer and ARDS), in each case supporting the association of CEC number with disease severity. We also argue for the utility of single-cell RNA transcriptomics to the understanding of cell-specific contributions to disease pathophysiology, and its potential to uncover novel insight on signals contributing to CEC shedding in ARDS.

show abstract

“…As such, it is necessary to understand endothelial phenotype and phenotype determination to build a multiscale model of developmental vascular remodelling. Recent advance in experimental techniques, such as single-cell RNA sequencing, have rapidly extended our understanding of the mechanisms controlling phenotype determination and network organisation [1,46]. Although there is still much left to understand, from recent studies, it is clear that a range of genetic factors and cellular signalling factors are the primary mechanisms regulating phenotype determination, while blood flow provides an auxiliary role [47][48][49][50][51].…”

Section: Vascular Identity Determinationmentioning

confidence: 99%

“…Coupling multicellular and subcellular scales: Endothelial cells behaviour is governed by processes occurring at the subcellular level. Existing models of remodelling at the multicellular scale (Section 4) assume that the endothelial population responds in a spatially and temporally uniform manner [52,78,79]; however, experimental studies show endothelial behaviour can vary significantly both within and between populations [45,46,[112][113][114][115]. Integrating the subcellular processes occurring within each cell with a larger cell-based model will be critical in providing a rigorous description of remodelling.…”

Section: Coupling Vessel and Multicellular Scalesmentioning

confidence: 99%

Mathematical models of developmental vascular remodelling: A review

Crawshaw¹,

Flegg²,

Bernabéu³

et al. 2023

PLoS Comput Biol

View full text Add to dashboard Cite

Over the past 40 years, there has been a strong focus on the development of mathematical models of angiogenesis, while developmental remodelling has received little such attention from the mathematical community. Sprouting angiogenesis can be seen as a very crude way of laying out a primitive vessel network (the raw material), while remodelling (understood as pruning of redundant vessels, diameter control, and the establishment of vessel identity and hierarchy) is the key to turning that primitive network into a functional network. This multiscale problem is of prime importance in the development of a functional vasculature. In addition, defective remodelling (either during developmental remodelling or due to a reactivation of the remodelling programme caused by an injury) is associated with a significant number of diseases. In this review, we discuss existing mathematical models of developmental remodelling and explore the important contributions that these models have made to the field of vascular development. These mathematical models are effectively used to investigate and predict vascular development and are able to reproduce experimentally observable results. Moreover, these models provide a useful means of hypothesis generation and can explain the underlying mechanisms driving the observed structural and functional network development. However, developmental vascular remodelling is still a relatively new area in mathematical biology, and many biological questions remain unanswered. In this review, we present the existing modelling paradigms and define the key challenges for the field.

show abstract

Comprehensive phenotyping of endothelial cells using flow cytometry 2: Human

Cited by 11 publications

References 113 publications

Single-Cell RNA Sequencing of Human Corpus Cavernosum Reveals Cellular Heterogeneity Landscapes in Erectile Dysfunction

Single-Cell RNA Sequencing of Human Corpus Cavernosum Reveals Cellular Heterogeneity Landscapes in Erectile Dysfunction

Are circulating endothelial cells the next target for transcriptome-level pathway analysis in ARDS?

Mathematical models of developmental vascular remodelling: A review

Contact Info

Product

Resources

About