Pluto Biosciences, Inc

GSE120379: Deep proteomic analysis of murine erythroid differentiation

Bulk RNA sequencing

Deciphering cellular proteomes is critical for our understanding of erythropoiesis. To better comprehend commonly used models of erythropoiesis, we obtained absolute quantification of proteins expressed in cultured primary murine bone-marrow derived erythroblasts throughout erythroid differentiation. These data were compared to proteomes from Friend murine erythroleukemia (MEL), G1ER, and MEDEP cells. Overall, more than 7200 proteins were quantified in at least one of these models of murine erythropoiesis. Protein expression during differentiation of MEDEP cells was most similar to that of differentiating primary murine erythroid cells, while proteomes of Friend MEL and G1ER cells were more distantly related. Comparison of the proteomes of murine and human erythroblasts revealed species-linked variability, but these differences were not as dramatic as those observed comparing human and murine transcriptomes during erythroid differentiation. To functionally validate the differences between transcriptional and translational control, heme synthesis was inhibited in MEDEP cells and the effects on the transcriptome and the proteome examined. While heme deficiency had minimal global effect on the cellular proteome, globin proteins were significantly down regulated, supporting observations heme regulation of globin synthesis is tightly regulated at the protein level to avoid deleterious over production of globin chains. As predicted, heme deficiency led to up regulation of -aminolevulinic acid synthase 2 (Alas2) protein. Interestingly, Alas1 was upregulated at both the transcriptional and protein levels. Characterization of cellular proteomes during erythropoiesis has potential to yield insight into mechanistic principles of human disease, as well as reveal novel therapeutic targets. SOURCE: Vince Schulz (vincent.schulz@yale.edu) - Gallagher Yale University

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