TSC-mTOR maintains quiescence and function of hematopoietic stem cells by repressing mitochondrial biogenesis and reactive oxygen species

Chen C, Liu Yu, Liu R, Ikenoue T, Guan KL, Liu Yang, Zheng P · 2008 · Journal of Experimental Medicine · Atlas ID CHE2008

What this study shows

Showed why blood stem cells must keep mTOR LOW. Deleting TSC1 (which unleashes mTOR) drove resting stem cells into rapid division, flooded them with reactive oxygen species, and burned out their ability to self-renew. An antioxidant rescued them. A key link between mTOR, stem-cell exhaustion, and tissue aging.

Abstract

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The tuberous sclerosis complex (TSC)-mammalian target of rapamycin (mTOR) pathway is a key regulator of cellular metabolism. We used conditional deletion of Tsc1 to address how quiescence is associated with the function of hematopoietic stem cells (HSCs). We demonstrate that Tsc1 deletion in the HSCs drives them from quiescence into rapid cycling, with increased mitochondrial biogenesis and elevated levels of reactive oxygen species (ROS).

Read the full abstract on PubMed →

At a glance

Evidence type	A Animal model Marked A because it is an animal intervention or observation study measuring an organismal outcome (model: Mouse (conditional Tsc1 knockout)); the code names the system studied -- animal work can be rigorous and still not be human data.
Study type	4 - Animal Study
Model system	Mouse (conditional Tsc1 knockout)
Journal	Journal of Experimental Medicine
Year	2008
Peer reviewed	Yes
Record last updated	2026-10-01
Source	DOI 10.1084/jem.20081297 · PMID 18809716 · Free full text (PMC2556783)

Extracted findings

These fields were extracted from the paper with AI assistance and have not been checked against the source. Read them as a pointer into the paper, not as curated claims; where they disagree with the curated summary above, the curated summary stands.

Intervention	Genetic (Tsc1 conditional knockout)
Target	TSC-mTOR / mitochondrial biogenesis / ROS
Model	Mouse (conditional Tsc1 KO)
Effect	TSC-mTOR maintains hematopoietic stem cell quiescence and function by repressing mitochondrial biogenesis and ROS
Dose	Mice (6 wk old) treated with polyinosine-polycytidine (pIpC) every other day for 2 wk to induce Tsc1 deletion.
Sample size	Variable, e.g., n=3 to n=10 mice per group depending on the experiment.
Effect size	Tsc1 deletion reduced quiescent LT-HSCs from ~70% to <15% and increased BrdU incorporation nearly fourfold (from 13% to ~60%); resulted in an ~50% reduction in white blood cell counts (P = 0.001).
Limitations	It is unlikely that the HSCs in the spleen are fully functional because HSCs have reduced self-renewal when their niche in BM is disrupted.

In the Atlas

Links in the pathway map

Supports mTORC1 activates Reactive oxygen species

Cite this paper

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Chen, C., Liu Yu, Liu, R., Ikenoue, T., Guan, K. L., Liu Yang, & Zheng, P. (2008). TSC-mTOR maintains quiescence and function of hematopoietic stem cells by repressing mitochondrial biogenesis and reactive oxygen species. Journal of Experimental Medicine. https://doi.org/10.1084/jem.20081297

@article{CHE2008,
  author       = {Chen, C. and Liu Yu and Liu, R. and Ikenoue, T. and Guan, K. L. and Liu Yang and Zheng, P.},
  title        = {{TSC-mTOR maintains quiescence and function of hematopoietic stem cells by repressing mitochondrial biogenesis and reactive oxygen species}},
  journal      = {Journal of Experimental Medicine},
  year         = {2008},
  doi          = {10.1084/jem.20081297},
  note         = {PMID: 18809716},
}

Cite this Atlas record

The record is the Atlas's own work — the evidence label, the extracted findings and the links. It is cited as part of the dataset, not as the paper.

Barton, O. (2026). Oliver's mTOR Atlas (record CHE2008) [Data set]. https://mtor-atlas.org/study/CHE2008/ · Dataset DOI 10.5281/zenodo.22059963

@misc{atlas_CHE2008,
  author       = {Barton, Oliver},
  title        = {{Oliver's mTOR Atlas}, record CHE2008},
  howpublished = {Data set},
  year         = {2026},
  url          = {https://mtor-atlas.org/study/CHE2008/},
  doi          = {10.5281/zenodo.22059963}
}

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