Identifying the functions of two biomarkers in human oligodendrocyte progenitor cell development

Haipeng Zhou,Xiaohua Wang,Ke Li,Zhaoyan Wang,Ying He,Qian Wang,Caiyan Hu,Zuo Luan,Yinxiang Yang,Siliang Lu

doi:10.1186/s12967-021-02857-8

Abstract

BackgroundHuman oligodendrocyte precursor cells (hOPCs) are an important source of myelinating cells for cell transplantation to treat demyelinating diseases. Myelin oligodendrocytes develop from migratory and proliferative hOPCs. It is well known that NG2 and A2B5 are important biological markers of hOPCs. However, the functional differences between the cell populations represented by these two biomarkers have not been well studied in depth.ObjectiveTo study the difference between NG2 and A2B5 cells in the development of human oligodendrocyte progenitor cells.MethodsUsing cell sorting technology, we obtained NG2+/−, A2B5+/− cells. Further research was then conducted via in vitro cell proliferation and migration assays, single-cell sequencing, mRNA sequencing, and cell transplantation into shiverer mice.ResultsThe proportion of PDGFR-α + cells in the negative cell population was higher than that in the positive cell population. The migration ability of the NG2+/−, A2B5+/− cells was inversely proportional to their myelination ability. The migration, proliferation, and myelination capacities of the negative cell population were stronger than those of the positive cell population. The ability of cell migration and proliferation of the four groups of cells from high to low was: A2B5− > NG2− > NG2+ > A2B5+. The content of PDGFR-α+ cells and the ability of cell differentiation from high to low was: NG2− > A2B5− > A2B5+ > NG2+.ConclusionIn summary, NG2+ and A2B5+ cells have poor myelination ability due to low levels of PDGFR-α+ cells. Therefore, hOPCs with a higher content of PDGFR-α+ cells may have a better effect in the cell transplantation treatment of demyelinating diseases.

Highlights

Human oligodendrocyte precursor cells are an important source of myelinating cells for cell transplantation to treat demyelinating diseases
HOPCs with a higher content of Platelet-derived growth factor receptor alpha (PDGFR-α)+ cells may have a better effect in the cell transplantation treatment of demyelinating diseases
In this study we investigated the differences in the proliferation, migration, and myelination ability of Chondroitin sulphate proteoglycan 4 (NG2)+/− and A2B5+/− cells during the development of Human oligodendrocyte precursor cells (hOPCs), and found that the migration ability of hOPCs may be inversely proportional to their myelination ability

Summary

Introduction

Human oligodendrocyte precursor cells (hOPCs) are an important source of myelinating cells for cell transplantation to treat demyelinating diseases. Current clinical methods for the treatment of demyelinating disease, in addition to more mature immunotherapy, focus on cell transplantation therapies. The transplanted cell types consist mainly of human oligodendrocyte progenitor cells (hOPCs) and mature human oligodendrocytes (OLs). These cells may be obtained directly from foetal and adult brain tissues [2,3,4] or through induced embryonic stem cells (ESCs) [5, 6] or induced pluripotent stem cells (iPSCs) [7, 8]. It is necessary to select a cell population that is most conducive to myelin regeneration after transplantation

Methods

Results

Discussion

Conclusion