Ganglioside expression delineates human mesenchymal stem/stromal cell populations derived from different tissue...

Area of Science:

• Cell Biology
• Glycobiology
• Stem Cell Biology

Background:

• Human embryonic stem cells differ from other mammals via glycosphingolipid (GSL) expression.
• Mesenchymal stem/stromal cells (MSCs) from bone marrow (BM-MSCs) and adipose tissue (A-MSCs) are promising for therapeutics.
• No surface markers currently distinguish culture-expanded BM-MSCs from A-MSCs.

Purpose of the Study:

• To investigate if GSL display can phenotypically define subsets of human adult stem cell populations.
• To characterize and compare GSL profiles of BM-MSCs and A-MSCs.

Main Methods:

• Isolation and mass spectrometry analysis (MALDI-QIT-TOF) of GSLs from BM-MSCs and A-MSCs.
• Flow cytometry to assess glycan determinant expression levels.
• RT-qPCR to measure gene expression of key enzymes in GSL biosynthesis.

Main Results:

• Neither BM-MSCs nor A-MSCs express significant lacto-series or neolacto-series GSLs.
• BM-MSCs, but not A-MSCs, dominantly express ganglio-series GSLs GD3 and GD2, and globo-series GSL SSEA-4.
• Differential expression of GD3 synthase, GM2/GD2 synthase, and Gb5 synthase genes underlies these GSL differences.
• GD3, GD2, and SSEA-4 expression is cell-intrinsic to BM-MSCs and diminishes upon differentiation.

Conclusions:

• GSL profiles stratify human MSCs based on tissue source, defining distinct "glycosignatures".
• Expression of GD3, GD2, and SSEA-4 is a cell-intrinsic, lineage-specific feature of BM-MSCs.
• Understanding MSC glycosignatures can inform cytotherapeutic strategies.