Journal article
mTORC1 pathway activity biases cell fate choice
- Abstract:
- Pluripotent stem cells can differentiate into distinct cell types but the intracellular pathways controlling cell fate choice are not well understood. The social amoeba Dictyostelium discoideum is a simplified system to study choice preference as proliferating amoebae enter a developmental cycle upon starvation and differentiate into two major cell types, stalk and spores, organised in a multicellular fruiting body. Factors such as acidic vesicle pH predispose amoebae to one fate. Here we show that the mechanistic target of rapamycin complex 1 (mTORC1) pathway has a role in cell fate bias in Dictyostelium. Inhibiting the mTORC1 pathway activity by disruption of Rheb (activator Ras homolog enriched in brain), or treatment with the mTORC1 inhibitor rapamycin prior to development, biases cells to a spore cell fate. Conversely activation of the pathway favours stalk cell differentiation. The Set1 histone methyltransferase, responsible for histone H3 lysine4 methylation, in Dictyostelium cells regulates transcription at the onset of development. Disruption of Set1 leads to high mTORC1 pathway activity and stalk cell predisposition. The ability of the mTORC1 pathway to regulate cell fate bias of cells undergoing differentiation offers a potential target to increase the efficiency of stem cell differentiation into a particular cell type.
- Publication status:
- Published
- Peer review status:
- Peer reviewed
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(Preview, Version of record, pdf, 2.1MB, Terms of use)
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(Preview, Supplementary materials, pdf, 3.8MB, Terms of use)
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- Publisher copy:
- 10.1038/s41598-024-71298-2
Authors
+ National Centre for the Replacement Refinement and Reduction of Animals in Research
More from this funder
- Funder identifier:
- https://ror.org/02w0kg036
- Publisher:
- Springer Nature
- Journal:
- Scientific Reports More from this journal
- Volume:
- 14
- Issue:
- 1
- Article number:
- 20832
- Publication date:
- 2024-09-06
- Acceptance date:
- 2024-08-27
- DOI:
- EISSN:
-
2045-2322
- Language:
-
English
- Keywords:
- Pubs id:
-
2025805
- Local pid:
-
pubs:2025805
- Source identifiers:
-
2243251
- Deposit date:
-
2024-09-06
Terms of use
- Copyright holder:
- Wang et al.
- Copyright date:
- 2024
- Rights statement:
- © The Author(s) 2024. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.
- Licence:
- CC Attribution (CC BY)
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