The characteristics of vessel lining cells in normal spleens and their role in the pathobiology of myelofibrosis

Abstract

Key Points• SVECs support the development of hematopoiesis in MF.• LCs and SVECs each have distinct properties and functions that differ between normal and MF spleens.

Single-Cell Transcriptome Atlas of Murine Endothelial Cells

“…For instance, consistent with their known blood-tissue barrier to secure strict homeostasis of the microenvironment and tight control of trans-endothelial cellular migration and solute transport (Su et al, 2011;Sweeney et al, 2019), brain and testis ECs highly expressed genes involved in transport processes. ECs from liver and spleen upregulated genes involved in scavenging and immuno-regulation, in agreement with their known role in scavenging pathogens, dead cells, and molecules (Qiu et al, 2018;Seternes et al, 2002) and the fact that the spleen regulates immune responses against pathogens (Bronte and Pittet, 2013), and the liver is under constant threat of an invasion by intestinal pathogens into the circulation (Poisson et al, 2017). ECs from especially the lung highly expressed MHC class II genes, suggesting a role in immune surveillance (Goveia et al, 2020).…”

The scavenger receptor SCARA5 is an endocytic receptor for von Willebrand factor expressed by littoral cells in the human spleen

“…Here, we observed that SCARA5 was expressed predominantly in the white pulp of the human spleen, but also expressed by CD31‐positive endothelial cells in the splenic red pulp, but not by CD68‐expressing macrophages (Figure ). In a systematic characterization of CD45‐depleted and FACs purified human splenic microvascular endothelial cells, CD31 + CD34 − CD8α + littoral cells, have been previously demonstrated to express a series of scavenger receptors including stabilin‐1, stabilin‐2, the macrophage mannose receptor CD206, and SCARA5 by mRNA analysis . Consistent with this observation, both VWF and SCARA5 colocalized with CD8α expressing cells within the red pulp of the spleen in sinusoidal‐like structures (Figure A).…”

“…Although the human IHC analysis cannot definitively demonstrate if VWF/SCARA5 coexpressing cells are producing and/or clearing this VWF, our VWF infusion data suggest that at least a portion of the VWF observed in these cells has been endocytosed. Moreover, a previously published microarray analysis of total RNA from FACS‐isolated littoral cells did not identify VWF expression as being either significantly upregulated or downregulated when compared with a reference pool . It is therefore plausible that along with stabilin‐2 and possibly other receptors, expression of SCARA5 in the splenic sinusoids contributes to the clearance of VWF in humans.…”

“…Previously, the mRNA expression of SCARA5 in splenic littoral (CD31 + CD34 − CD8α + ) but not splenic vascular endothelial cells (CD31 + CD34 + CD8α − ) has been reported . Using the same CD8α and CD34 antibodies that have been previously validated for the isolation of these two cell populations by FACs, we performed IHC on human spleen samples and costained for SCARA5 and VWF.…”

“…In mice, SCARA5 is expressed by epithelial cells and fibroblasts in the testis, heart, brain, and spleen . In contrast, the expression pattern of SCARA5 in human tissues is largely uncharacterized, although SCARA5 mRNA is expressed in CD31 + CD34 − CD8α + littoral cells, a subtype of splenic sinusoidal endothelial cells . In this report, we describe the ability of SCARA5 to bind and/or internalize VWF using cell expression and solid phase‐binding assays.…”