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

• Published in: Experimental hematology Vol. 96; pp. 44 - 51
• Main Authors: Termini, Christina M., Pang, Amara, Batton, Destiny M., Chute, John P.
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier Inc 01.04.2021
• Subjects: Animals; Cells, Cultured; Cytoskeletal Proteins - metabolism; Hematopoietic Stem Cells - cytology; Hematopoietic Stem Cells - metabolism; Mice, Inbred C57BL; Proteoglycans - analysis; Proteoglycans - metabolism; Receptor-Like Protein Tyrosine Phosphatases, Class 2 - analysis; Receptor-Like Protein Tyrosine Phosphatases, Class 2 - metabolism; Syndecan-2 - analysis; Syndecan-2 - metabolism
• ISSN: 0301-472X; 1873-2399
• DOI: 10.1016/j.exphem.2021.01.005

•Syndecan-2 promotes clustering of PTPσ on hematopoietic stem/progenitor cells.•STED microscopy allows molecular co-localization in HSPCs.•Syndecan-2 promotes ezrin activation and HSPC growth. Protein tyrosine phosphatase receptor σ (PTPσ) 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 PTPσ by clustering PTPσ 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 PTPσ in hematopoietic stem/progenitor cells (HSPCs). Our study illustrates that syndecan-2 promotes PTPσ clustering, which sustains phospho-tyrosine and phospho-ezrin levels in association with augmentation of hematopoietic colony formation. Strategies that promote clustering of PTPσ on HSPCs may serve to powerfully augment hematopoietic function. [Display omitted]