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Updated: Feb 17, 2026
Optimized Quantitative Assessment of Enhancer RNA Stability in Mouse Embryonic Stem Cells
Published on: November 21, 2025
Genome-wide RNA-Seq identifies Fas/FasL-mediated tumoricidal activity of embryonic stem cells
Yatong Li1,2,3, Yongna Fan2, Jing Xu1,2
1Department of General Surgery, Peking Union Medical College Hospital, Beijing, 100730, China.
Abstract:
The discovery of tumor tropism of stem cells revealed the intimate relationship between stem cells and tumor cells, but the functional role of stem cells in tumorigenesis is poorly understood. To investigate embryonic stem cell (ESC) and tumor cell interactions, we co-cultured mouse ESCs with mouse melanoma B16-F10 cells or mouse pancreatic tumor Pan02 cells, and found that ESCs significantly inhibited tumor cell proliferation. Coculture of ESCs and tumor cells resulted in significant inhibition of tumorigenesis in vivo. Histological analyses indicated that ESCs encircled apoptotic tumor cells. We carried out time course RNA-Seq analyses of ESC and tumor cell co-cultures, and identified Fas/FasL signaling as a major pathway involved in ESC-mediated apoptosis of tumor cells. We further generated FADD-deficient tumor cells by CRISPR/Cas9-mediated gene editing, and demonstrated that FADD-deficient tumor cells were obviously resistant to ESC-mediated inhibition of tumor cell proliferation. Our results indicate the Fas/FasL signaling pathway plays a critical role in ESCs-mediated tumoricidal activity.
Insights
Embryonic stem cells (ESCs) can inhibit tumor growth by inducing cancer cell death. This study identifies the Fas/FasL signaling pathway as crucial for this tumoricidal activity, offering new insights into stem cell-based cancer therapies.
Area of Science:
- Oncology
- Stem Cell Biology
- Molecular Biology
Background:
- Stem cells exhibit tumor tropism, suggesting a link between stem cells and cancer.
- The precise role of stem cells in tumorigenesis remains unclear.
Purpose of the Study:
- To investigate the interaction between embryonic stem cells (ESCs) and tumor cells.
- To elucidate the mechanisms underlying ESC-mediated inhibition of tumor growth.
Main Methods:
- Co-culture of mouse ESCs with melanoma and pancreatic tumor cells.
- In vivo tumorigenesis inhibition assays.
- Time-course RNA-Seq analysis.
- CRISPR/Cas9 gene editing to generate FADD-deficient tumor cells.
Main Results:
- ESCs significantly inhibited tumor cell proliferation in vitro and suppressed tumorigenesis in vivo.
- Histological analysis revealed ESCs surrounding apoptotic tumor cells.
- RNA-Seq identified Fas/FasL signaling as a key pathway.
- FADD-deficient tumor cells showed resistance to ESC-mediated growth inhibition.
Conclusions:
- Embryonic stem cells possess tumoricidal activity against melanoma and pancreatic tumors.
- The Fas/FasL signaling pathway is critical for ESC-mediated apoptosis of tumor cells.
- Targeting the Fas/FasL pathway could enhance stem cell-based cancer therapies.
