Erythroid Lineage Cells in the Liver: Novel Immune Regulators and Beyond

Abstract

The lineage of the erythroid cell has been revisited in recent years. Instead of being classified as simply inert oxygen carriers, emerging evidence has shown that they are a tightly regulated in immune potent population with potential developmental plasticity for lineage crossing. Erythroid cells have been reported to exert immune regulatory function through secreted cytokines, or cell-cell contact, depending on the conditions of the microenvironment and disease models. In this review, we explain the natural history of erythroid cells in the liver through a developmental lens, as it offers perspectives into newly recognized roles of this lineage in liver biology. Here, we review the known immune roles of erythroid cells and discuss the mechanisms in the context of disease models and stages. Then, we explore the capability of erythroid lineage as a cell source for regenerative medicine. We propose that the versatile lineage of erythroid cells provides an underappreciated and potentially promising area for basic and translational research in the field of liver disease.

Generation of Red Blood Cells from Human Pluripotent Stem Cells—An Update

“…The erythroid lineage cells represent erythroblasts to erythrocytes. These cells express transferrin receptor (TFRC; CD71), solute carrier family 4 member 1 (SLC4A1; BND3), and glycophorin A (GYPA; CD235A) [13] (Figure 3). In addition to these conventional RBC markers, CD36 and CD44 have been also used to distinguish erythroblasts from TFRC + cells in different developmental stages [14].…”

A single-nucleus and spatial transcriptomic atlas of the COVID-19 liver reveals topological, functional, and regenerative organ disruption in patients

“…Moreover, erythrocyte precursors (ERY-P) were detected almost exclusively in the COVID-19 liver (FDR=2.37×10 −6 , OR=12.554, Binomial GLMM), expressing a combination of hemoglobin and glycophorin genes, proliferation genes, and additional genes not present in mature red blood cells, such as CD71/ TFRC , which are rarely encountered outside the bone marrow in adults. These cells may be responsible for extramedullary hematopoiesis in the setting of hypoxia, modulate immune response in virus infection, and participate in hepatogenesis as shown in fetal liver 38,39 .…”