Blood: Endotopic mesh-related degradation maintains the static and self-renewal of hematopoietic stem cells by limiting mTOR activity

Hematopoietic stem cells (HSCs) can be self-renewed to maintain stem cell bank and can differentiate to produce various types of blood cells.
hematopoietic stem cells remain stationary to maintain their long-term self-renewal potential.
is not clear whether still stem cells need protein quality control when RNA content, protein synthesis, and metabolic activity are significantly reduced.
recently, the latest issue of "ER associated degradation preserves hematopoietic stem cell quiescence and self-renewal by restricting mTOR activity" reported that the protein quality controlled by endosperm-related degradation (ERAD) regulates the function of resting hematopoietic stem cells (HSCs).
Sel1L/Hrd1 ERAD gene is rich in stationary and inactive hematopoietic stem cells in stationary and inactive hematopoietic stem cells, Sel1L/Hrd1 ERAD gene is rich, and conditional knock-out of Sel1L in hematopoietic tissue can lead to excessive proliferation of HSC, resulting in the complete loss of HSC self-renewal capacity, resulting in HSC depletion.
the absence of Sel1L leads to excessive proliferation and activation of HSC on the mechanism, by knocking out the Sel1L gene leads to ERAD defects, which in turn activates the mTOR signal.
addition, the researchers found that the mTOR activator Rheb is a new protein substrate of Sel1L/Hrd1 ERAD, which accumulates when Sel1L is missing and HSC is activated.
important, inhibiting mTOR or Rheb can save the Sel1L gene from knocking out HSC defects in mice.
above, protein quality control via ERAD is a key checkpoint that regulates the stillness and self-renewal of HSC through Therb-mediated mTOR activity limits.