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

Christina M Termini; Amara Pang; Destiny M Batton; John P Chute

doi:10.1016/j.exphem.2021.01.005

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

Exp Hematol. 2021 Apr:96:44-51. doi: 10.1016/j.exphem.2021.01.005. Epub 2021 Jan 27.

Authors

Christina M Termini¹, Amara Pang², Destiny M Batton³, John P Chute⁴

Affiliations

¹ Division of Hematology/Oncology, Department of Medicine, University of California at Los Angeles, Los Angeles, CA; Department of Orthopaedic Surgery, University of California at Los Angeles, Los Angeles, CA; Department of Medicine, Cedars Sinai Medical Center, Los Angeles, CA.
² Division of Hematology/Oncology, Department of Medicine, University of California at Los Angeles, Los Angeles, CA; Department of Medicine, Cedars Sinai Medical Center, Los Angeles, CA.
³ Division of Hematology/Oncology, Department of Medicine, University of California at Los Angeles, Los Angeles, CA.
⁴ Division of Hematology/Oncology, Department of Medicine, University of California at Los Angeles, Los Angeles, CA; Department of Orthopaedic Surgery, University of California at Los Angeles, Los Angeles, CA; Department of Medicine, Cedars Sinai Medical Center, Los Angeles, CA; Broad Stem Cell Research Center, University of California at Los Angeles, Los Angeles, CA; Jonsson Comprehensive Cancer Center, University of California at Los Angeles, Los Angeles, CA. Electronic address: john.chute@cshs.org.

Abstract

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.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

Animals
Cells, Cultured
Cytoskeletal Proteins / metabolism
Hematopoietic Stem Cells / cytology
Hematopoietic Stem Cells / metabolism*
Mice
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

Substances

Cytoskeletal Proteins
Proteoglycans
Sdc2 protein, mouse
ezrin
Syndecan-2
Ptprs protein, mouse
Receptor-Like Protein Tyrosine Phosphatases, Class 2

Abstract

Publication types

MeSH terms

Substances

Grants and funding