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mTORC1 pathway activity biases cell fate choice
Yuntao Wang1, Monika Papayova1, Eleanor Warren1
1Department of Biochemistry, University of Oxford, South Parks Road, Oxford, OX1 3QU, UK.
Scientific Reports
|September 6, 2024
Summary
The mechanistic target of rapamycin complex 1 (mTORC1) pathway influences cell fate decisions in Dictyostelium amoebae. Manipulating mTORC1 activity can bias differentiation towards spore or stalk cell types, offering insights into stem cell differentiation.
Area of Science:
- Cell Biology
- Developmental Biology
- Biochemistry
Background:
- Pluripotent stem cells differentiate into various cell types, but the underlying intracellular pathways governing cell fate are not fully understood.
- The social amoeba Dictyostelium discoideum provides a model system for studying cell fate choice, differentiating into stalk and spore cells during development.
- Factors like acidic vesicle pH can influence cell fate predisposition in Dictyostelium.
Purpose of the Study:
- To investigate the role of the mechanistic target of rapamycin complex 1 (mTORC1) pathway in regulating cell fate bias in Dictyostelium.
- To explore how modulating mTORC1 activity affects the differentiation of amoebae into specific cell types.
- To examine the relationship between Set1 histone methyltransferase activity, mTORC1 signaling, and cell fate determination.
Main Methods:
- Utilizing Dictyostelium discoideum as a model organism for developmental studies.
- Manipulating mTORC1 pathway activity through Rheb disruption and rapamycin treatment.
- Assessing cell fate bias towards spore or stalk differentiation.
- Investigating the function of Set1 histone methyltransferase and its impact on mTORC1 activity and cell fate.
Main Results:
- Inhibition of mTORC1 signaling, via Rheb disruption or rapamycin, resulted in a bias towards spore cell fate.
- Activation of the mTORC1 pathway favored stalk cell differentiation.
- Disruption of Set1 led to elevated mTORC1 activity and a predisposition for stalk cell differentiation.
Conclusions:
- The mTORC1 pathway plays a significant role in determining cell fate bias during Dictyostelium differentiation.
- Modulating mTORC1 activity offers a potential strategy to enhance the efficiency of stem cell differentiation into desired cell types.
- Set1 histone methyltransferase influences cell fate through regulation of mTORC1 pathway activity.
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