Proteomic dissection of human erythropoiesis reveals critical roles of kinases

ABSTRACT: Human erythropoiesis is exquisitely controlled at multiple levels and its dysregulation leads to anemias and many other diseases. We apply mass spectrometry (MS)-based proteomics to comprehensively investigate the protein and signaling dynamics of this process. Mapping the proteomes and phosphoproteomes of five defined stages from progenitors to erythrocytes, quantifies more than 7,400 protein groups and 27,000 distinct phosphorylation sites. Integration with a transcriptomic dataset reveals discordances that are biologically meaningful. Solute carriers are drastically remodeled and provide new stage-specific markers. Our data reveal an orchestrated network of erythropoietic kinases involving erythropoietin receptor and downstream MAPK signaling. A subsequent CRIPR screen verified their functional roles in state specific transitions. In particular, the PIM1 kinase maintains proliferative capacity of erythroid progenitors and prevents premature differentiation. Our comprehensive resource thus provides conceptual insights into an important developmental process and a plethora of starting points for mechanistic studies in health and disease.

INSTRUMENT(S): Q Exactive HF

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Erythrocyte, Cell Culture, Blood

SUBMITTER: Mario Oroshi  

LAB HEAD: Matthias Mann

PROVIDER: PXD017276 | Pride | 2020-10-20

REPOSITORIES: pride