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Assessment of Selective mRNA Translation in Mammalian Cells by Polysome Profiling
Published on: October 28, 2014
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Ribosome impairment regulates intestinal stem cell identity via ZAKɑ activation.
Joana Silva1, Ferhat Alkan1, Sofia Ramalho1
1Division of Oncogenomics, The Netherlands Cancer Institute, Amsterdam, The Netherlands.
Nature Communications
|August 2, 2022
Summary
Ribosome impairment triggers a shift in intestinal stem cells (ISCs) to a fetal-like state, revealing the ribosome
Area of Science:
- Stem cell biology
- Gastrointestinal physiology
- Molecular mechanisms of cell plasticity
Background:
- Intestinal stem cells (ISCs) maintain the rapidly proliferating small intestine.
- Lgr5-expressing ISCs are crucial, but Lgr5-negative populations also exist.
- The mediators of ISC plasticity remain largely unknown.
Purpose of the Study:
- To investigate the role of ribosome function in ISC plasticity.
- To identify mediators that govern ISC identity changes in response to environmental cues.
Main Methods:
- Utilized intestinal organoid models and mouse models.
- Induced ribosome impairment through Rptor deletion, amino acid starvation, and low-dose cyclohexamide.
- Analyzed metabolic rewiring and molecular signaling pathways.
Main Results:
- Ribosome impairment induced ISCs to acquire an Lgr5-negative, fetal-like identity.
- Observed significant metabolic rewiring in response to ribosome stress.
- Identified ZAKɑ activation, leading to YAP activation via SRC, as a key mechanism.
Conclusions:
- The ribosome functions as a nutrient sensor, mediating ISC responses to the local environment.
- Ribosome dynamics play a central role in maintaining intestinal stem cell identity.
- ZAKɑ activation is a critical mediator of ISC plasticity and identity.
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