Proteoglycans regulate protein tyrosine phosphatase receptor σ organization on hematopoietic stem/progenitor cells

Protein tyrosine phosphatase receptor o- (PTPo-) is highly expressed by murine and human hematopoietic stem cells (HSCs) and negatively regulates HSC self-renewal and regeneration. Previous studies of the nervous system suggest that heparan sulfate proteoglycans can inactivate PTPo- by clustering PTPo- receptors on neurons, but this finding has yet to be visually verified with adequate resolution. Here, we sought to visualize and quantify how heparan sulfate proteoglycans regulate the organization and activation of PTPo- in hematopoietic stem/progenitor cells (HSPCs). Our study illustrates that syndecan-2 promotes PTPo- clustering, which sustains phospho-tyrosine and phospho-ezrin levels in association with augmentation of hematopoietic colony formation. Strategies that promote clustering of PTPo- on HSPCs may serve to powerfully augment hematopoietic function. ? 2021 Published by Elsevier Inc. on behalf of ISEH ? Society for Hematology and Stem Cells.

Automated summary

PTPo- is highly expressed by HSCs and negatively regulates their self-renewal and regeneration. Syndecan-2 promotes PTPo- clustering, leading to increased levels of phospho-tyrosine and phospho-ezrin in HSPCs and enhancing hematopoietic colony formation. Strategies that promote PTPo- clustering on HSPCs may have the potential to significantly boost hematopoietic function.