Profiling of H3K4me1 positioning in primary erythroid cells by CUT&RUN
Ontology highlight
ABSTRACT: The chromatin landscape of developing erythroblasts changes dramatically during differentiation. We have profiled the localisation of H3K4me1 in primary erythroid cells entering terminal differentiation using CUT&RUN.
Project description:The chromatin landscape of developing erythroblasts changes dramatically during differentiation. We have profiled the localisation of H3K4me3 in primary erythroid cells entering terminal differentiation using CUT&RUN.
Project description:The chromatin landscape of developing erythroblasts changes dramatically during differentiation. We have profiled the localisation of H3K27me3 in primary erythroid cells entering terminal differentiation using CUT&RUN.
Project description:The chromatin landscape of developing erythroblasts changes dramatically during differentiation. We have profiled the change in Gata1 binding in primary erythroid cells entering terminal differentiation using CUT&RUN.
Project description:The chromatin landscape of developing erythroblasts changes dramatically during differentiation. We have profiled the change in Gata2 binding in primary erythroid cells entering terminal differentiation using CUT&RUN.
Project description:The chromatin landscape of developing erythroblasts changes dramatically during differentiation. We have profiled the change in Nf-e2 binding in primary erythroid cells entering terminal differentiation using CUT&RUN.
Project description:Schneider RK, Schenone M, Kramann R, Ferreira MV, Joyce CE, Hartigan C, Beier F, Brümmendorf TH, Gehrming U, Platzbecker U, Buesche G, Chen MC, Waters CS, Chen E, Chu LP, Novina CD, Lindsley RC, Carr SA, Ebert BL. Nat Med, 2016.
Heterozygous deletion of RPS14 occurs in del(5q) MDS and has been linked to impaired erythropoiesis, characteristic of this disease subtype. We generated a murine model with conditional inactivation of Rps14 and demonstrated a p53-dependent erythroid differentiation defect with apoptosis at the transition from polychromatic to orthochromatic erythroblasts resulting in age-dependent progressive anemia, megakaryocyte dysplasia, and loss of hematopoietic stem cell (HSC) quiescence. Using quantitative proteomics, we identified significantly increased expression of proteins involved in innate immune signaling, particularly the heterodimeric S100A8/S100A9 proteins in purified erythroblasts. S100A8 expression was significantly increased in erythroblasts, monocytes and macrophages and recombinant S100A8 was sufficient to induce an erythroid differentiation defect in wild-type cells. We rescued the erythroid differentiation defect in Rps14 haploinsufficient HSCs by genetic inactivation of S100a8 expression. Our data link Rps14 haploinsufficiency to activation of the innate immune system via induction of S100A8/A9 and the p53-dependant erythroid differentiation defect in del(5q) MDS.
Project description:Nuclear receptor binding SET domain protein 1 (NSD1) is recurrently mutated in human cancers including acute leukemia. We found that NSD1 knockdown altered erythroid clonogenic growth of human CD34+ hematopoietic cells. Ablation of Nsd1 in the hematopoietic system induced a transplantable erythroleukemia in mice. Despite abundant expression of the transcriptional master regulator GATA1, in vitro differentiation of Nsd1-/- erythroblasts was majorly impaired associated with reduced activation of GATA1-induced targets, while GATA1-repressed target genes were less affected. Retroviral expression of wildtype Nsd1, but not a catalytically-inactive Nsd1N1918Q SET-domain mutant induced terminal maturation of Nsd1-/- erythroblasts. Despite similar GATA1 levels, exogenous Nsd1 but not Nsd1N1918Q significantly increased GATA1 chromatin occupancy and target gene activation. Notably, Nsd1 expression reduced the association of GATA1 with the co-repressor SKI, and knockdown of SKI induced differentiation of Nsd1-/- erythroblasts. Collectively, we identified the NSD1 methyltransferase as a novel regulator of GATA1-controlled erythroid differentiation and leukemogenesis.
Project description: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.
Project description:To gain the whole picture of terminal erythroid differentiation, bone marrow erythroblasts of different maturation stages including proerythroblasts (Pro),basophilic erythroblasts (Baso), polychromatic erythroblasts (Poly) and orthochromatic erythroblasts (Ortho) were isolated and sorted.Transcriptomic analysis of these four stages of cells was performed.