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Updated: Jul 9, 2026

Stimulation of Notch Signaling in Mouse Osteoclast Precursors
Published on: February 28, 2017
Nanog inhibits the switch of myogenic cells towards the osteogenic lineage
Bose S Kochupurakkal1, Rachel Sarig, Ora Fuchs
1Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot 76100, Israel.
Abstract:
The homeodomain transcription factor Nanog has been implicated in inhibiting differentiation and controlling pluripotency of embryonic stem (ES) cells. We used ectopic expression of Nanog in the myogenic committed C2 cells to dissect these properties. Expression of Nanog in C2 cells does not alter terminal muscle differentiation but has a profound effect on their switch to differentiate along the osteogenic lineage upon BMP treatment. Gene expression profiling revealed that ERK 1/2 phosphorylation, alkaline-phosphatase activity and osteocalcin expression were induced to much lower extent and remained suppressed even after 96h. in Nanog expressing C2 cells, compared to control C2 cells. Hence, Nanog does not inhibit terminal differentiation of committed cells but it is an inhibitor of trans-differentiation that is dependent on de-novo activation of gene transcription.
Insights
The homeodomain transcription factor Nanog controls pluripotency in embryonic stem cells. Nanog inhibits trans-differentiation of committed cells, not terminal differentiation, by blocking new gene transcription.
Area of Science:
- Stem cell biology
- Developmental biology
- Molecular genetics
Background:
- The homeodomain transcription factor Nanog is crucial for maintaining pluripotency in embryonic stem (ES) cells.
- Nanog's role in differentiation and lineage commitment requires further elucidation.
Purpose of the Study:
- To investigate the specific roles of Nanog in cellular differentiation and lineage plasticity.
- To determine if Nanog inhibits terminal differentiation or trans-differentiation in committed cells.
Main Methods:
- Ectopic expression of Nanog in mouse myogenic C2 cells.
- Assessment of terminal muscle differentiation.
- Induction of osteogenic differentiation using BMP treatment.
- Gene expression profiling and analysis of key differentiation markers (e.g., ERK 1/2 phosphorylation, alkaline phosphatase, osteocalcin).
Main Results:
- Nanog expression did not affect terminal muscle differentiation in C2 cells.
- Nanog significantly inhibited the osteogenic trans-differentiation of C2 cells upon BMP stimulation.
- Key osteogenic markers and signaling pathways (ERK 1/2) showed suppressed induction in Nanog-expressing cells.
Conclusions:
- Nanog acts as an inhibitor of trans-differentiation in committed cells.
- This inhibition is dependent on the de novo activation of gene transcription.
- Nanog's function is context-dependent, affecting lineage plasticity rather than terminal differentiation potential.
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