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Publication

mTORC1 Activation during Repeated Regeneration Impairs Somatic Stem Cell Maintenance.

Cell stem cell | 2017

The balance between self-renewal and differentiation ensures long-term maintenance of stem cell (SC) pools in regenerating epithelial tissues. This balance is challenged during periods of high regenerative pressure and is often compromised in aged animals. Here, we show that target of rapamycin (TOR) signaling is a key regulator of SC loss during repeated regenerative episodes. In response to regenerative stimuli, SCs in the intestinal epithelium of the fly and in the tracheal epithelium of mice exhibit transient activation of TOR signaling. Although this activation is required for SCs to rapidly proliferate in response to damage, repeated rounds of damage lead to SC loss. Consistently, age-related SC loss in the mouse trachea and in muscle can be prevented by pharmacologic or genetic inhibition, respectively, of mammalian target of rapamycin complex 1 (mTORC1) signaling. These findings highlight an evolutionarily conserved role of TOR signaling in SC function and identify repeated rounds of mTORC1 activation as a driver of age-related SC decline.

Pubmed ID: 29220665 RIS Download

Research resources used in this publication

None found

Additional research tools detected in this publication

Fiji (RRID:SCR_002285)

Antibodies used in this publication

Associated grants

Agency: NIDDK NIH HHS, United States
Id: R01 DK100342
Agency: NIA NIH HHS, United States
Id: K99 AG041764
Agency: NIA NIH HHS, United States
Id: R01 AG047820
Agency: NIA NIH HHS, United States
Id: R01 AG047497
Agency: NIA NIH HHS, United States
Id: P01 AG036695
Agency: NHLBI NIH HHS, United States
Id: R01 HL132996
Agency: NIA NIH HHS, United States
Id: R00 AG041764
Agency: BLRD VA, United States
Id: I01 BX002324
Agency: NIDDK NIH HHS, United States
Id: R01 DK113144

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This is a list of tools and resources that we have found mentioned in this publication.

Fiji (tool)

RRID:SCR_002285

Software package as distribution of ImageJ and ImageJ2 together with Java, Java3D and plugins organized into coherent menu structure. Used to assist research in life sciences.

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Monoclonal Anti-alpha-Tubulin antibody produced in mouse (antibody)

RRID:AB_477579

This monoclonal targets α-tubulin

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Cleaved Caspase-3 (Asp175) Antibody (antibody)

RRID:AB_2341188

This polyclonal targets Cleaved Caspase-3 (Asp175)

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Rat Anti-Laminin alpha-2 Monoclonal antibody, Unconjugated, Clone 4h8-2 (antibody)

RRID:AB_784266

This monoclonal targets LAMA2

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Pax7 antibody - Kawakami, A.; Tokyo Institute of Technology (antibody)

RRID:AB_528428

This monoclonal targets Pax7

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Acetylated Tubulin (antibody)

RRID:AB_609894

This monoclonal targets derived from the hybridoma 6-11B-1 produced by the fusion of mouse myeloma cells and splenocytes from a mouse immunized with acetylated tubulin from the outer arm of Strongylocentrotus purpuratus (sea urchin).

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