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Single-cell multiomics reveals stage of differentiation and trajectory-dependent immunity-related gene expression patterns in human erythroid cells

ABSTRACT: Erythroid cells, serving as progenitors and precursors to erythrocytes responsible for oxygen transport, exhibit a notable immunosuppressive and immunoregulatory phenotype. The present study CITE-seq reveals that erythroid cells have stage of differentiation-dependent immunity-related gene expression patterns. We also found that Erythroid cell differentiation is not linear and there is a bifurcation of polychromatophilic erythroblasts into ARG1 expressing polychromatophilic erythroblasts and orthochromatophilic erythroblasts. ARG1 expressing polychromatophilic erythroblasts account for almost all immunosuppressive ARG1 gene expression among erythroid cells. Thus, we infer the stepwise erythroid cells differentiation trajectory that has a branch that forms immunosuppressive erythroid cell population.

ORGANISM(S): Homo sapiens

PROVIDER: GSE261733 | GEO | 2024/03/20

REPOSITORIES: GEO

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Project description:It is unclear how epigenetic changes regulate the induction of erythroid-specific genes during terminal erythropoiesis. Here we use global mRNA sequencing (mRNA-seq) and chromatin immunoprecipitation coupled to high-throughput sequencing (CHIP-seq) to investigate the changes that occur in mRNA levels, RNA Polymerase II (Pol II) occupancy and multiple post-translational histone modifications when erythroid progenitors differentiate into late erythroblasts. Among genes induced during this developmental transition, there was an increase in the occupancy of Pol II, the activation marks H3K4me2, H3K4me3, H3K9Ac and H4K16Ac, and the elongation methylation mark H3K79me2. In contrast, genes that were repressed during differentiation showed relative decreases in H3K79me2 levels yet had levels of Pol II binding and active histone marks similar to those in erythroid progenitors. We also found that relative changes in histone modification levels-in particular, H3K79me2 and H4K16ac-were most predictive of gene expression patterns. Our results suggest that in terminal erythropoiesis both promoter and elongation-associated marks contribute to the induction of erythroid genes, while gene repression is marked by changes in histone modifications mediating Pol II elongation. Our data maps the epigenetic landscape of terminal erythropoiesis and suggests that control of transcription elongation regulates gene expression during terminal erythroid differentiation. Mouse fetal liver cells are double-labeled for erythroid-specific TER119 and non erythroid-specific transferrin receptor (CD71) and then sorted by flow-cytometry. E14.5 fetal livers contain at least five distinct populations of cells (R1 through R5); as they progressively differentiate they gain TER119 and then gain and subsequently lose CD71. CFU-E cells and proerythroblasts make up the R1 population; R2 consists of proerythroblasts and early basophilic erythroblasts; R3 includes early and late basophilic erythroblasts; R4 is mostly polychromatophilic and orthochromatophilic erythroblasts; and R5 is comprised of late orthochromatophilic erythroblasts and reticulocytes. We have sorted for R2-R5 cells for RNA-seq experiment.