Project #13848
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#13848 : Secretome Analysis of OIS IL6KO SASP
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Name of Applicant : Mathieu von Joest
Date of application : 17-09-2019
Unit : Cellular Plasticity And Disease Modelling
Location : Monod-1st floor-Room 07D
Phone : 0145683940
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Project context and summary :

Cellular senescence is a stable cell cycle arrest that can be triggered by various biological stresses. Importantly, senescent cells remain metabolically active and secrete numerous molecules, such as cytokines, chemokines, proteases and growth factors. This secretome is called SASP (senescence associated secretory phenotype). Senescence plays a role in several processes, most notably in cancer, where it acts as an intrinsic tumor suppressor mechanism by inhibiting cell growth of premalignant cells. More recently, senescence has been shown to be involved in other biological responses, notably in tissue repair and aging. We recently showed that senescence upon tissue damage was promoting cellular reprogramming and cellular plasticity, notably via SASP. More precisely, we showed that IL-6 was an important mediator of SASP effect. Blocking IL-6 abolished beneficial effect of the SASP on reprogramming. Nonetheless, we speculate that other factors may be important for reprogramming. Indeed SASP factors have been previously shown to play redundant roles, notably in mediating senescence. Therefore we performed mass spectrometry analysis to identify other SASP factors in collaboration with proteomic platform of Institut Pasteur. We already identified promising candidates but we would also like to have a better global understanding of SASP complexity and which pathways it could activate in recipient cells. Thus, to investigate SASP effects more in details, we collaborate with C3BI platform of Institut Pasteur. Finally, understanding how SASP impact cellular plasticity in the context to tissue regeneration is essential for devising new strategies based on in vivo reprogramming.

Related team publications :
Chiche A, Le Roux I, von Joest M, Sakai H, AguĂ­n SB, Cazin C, Salam R, Fiette L, Alegria O, Flamant P, Tajbakhsh S, Li H, Injury-Induced Senescence Enables In Vivo Reprogramming in Skeletal Muscle, Cell Stem Cell 2017 03;20(3):407-414.e4.
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Project Type : Short
Status : In Progress

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