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.
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.
Exp Hematol. 2021 Apr;96:44-51. doi: 10.1016/j.exphem.2021.01.005. Epub 2021 Jan 27.
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.
蛋白酪氨酸磷酸酯酶受体 σ（PTPσ）在鼠类和人类造血干细胞（HSCs）中高度表达，并负调控 HSC 自我更新和再生。先前对神经系统的研究表明，硫酸乙酰肝素蛋白聚糖可通过在神经元上聚集 PTPσ 受体来使 PTPσ 失活，但这一发现尚未用足够高的分辨率进行可视化验证。在这里，我们试图可视化和量化硫酸乙酰肝素蛋白聚糖如何调节造血干细胞/祖细胞（HSPCs）中 PTPσ 的组织和激活。我们的研究表明，连接蛋白-2 促进 PTPσ 聚集，从而维持磷酸酪氨酸和磷酸埃兹蛋白的水平，同时增强造血集落形成。促进 PTPσ 在 HSPCs 上聚集的策略可能会有力地增强造血功能。
