Interactions in CSF1-Driven Tenosynovial Giant Cell Tumors

Area of Science:

• Oncology
• Cell Biology
• Genomics

Background:

• Tenosynovial giant cell tumor (TGCT) involves neoplastic cells overproducing CSF1, stimulating bystander macrophages.
• An autocrine loop via CSF1R on neoplastic cells was hypothesized but unconfirmed.

Purpose of the Study:

• Investigate cellular interactions in TGCT using single-cell RNA sequencing (scRNA-seq).
• Characterize neoplastic cell populations and their molecular profiles.
• Identify potential therapeutic targets in TGCT.

Main Methods:

• scRNA-seq on 18,788 cells from TGCT and GCTB samples.
• Long-read RNA sequencing for TGCT samples.
• Immunofluorescence and immunohistochemistry (IHC) for validation.

Main Results:

• Identified two neoplastic cell populations in TGCT, similar to nonneoplastic synoviocytes.
• Discovered GFPT2 as a marker for TGCT neoplastic cells.
• Confirmed neoplastic cells lack CSF1R expression, challenging the autocrine loop hypothesis.

Conclusions:

• TGCT neoplastic cells are similar to synoviocytes and may not respond to CSF1R-targeted therapies.
• High GFPT2 expression correlates with YAP1/TAZ pathway activation.
• Platelet-derived growth factor receptor expression suggests novel therapeutic avenues.