Tissue damage and senescence provide critical signals for cellular reprogramming in vivo

Author:

Mosteiro Lluc1,Pantoja Cristina1,Alcazar Noelia1,Marión Rosa M.2,Chondronasiou Dafni1,Rovira Miguel1,Fernandez-Marcos Pablo J.13,Muñoz-Martin Maribel1,Blanco-Aparicio Carmen4,Pastor Joaquin4,Gómez-López Gonzalo5,De Martino Alba6,Blasco Maria A.2,Abad María17,Serrano Manuel1

Affiliation:

1. Tumor Suppression Group, Spanish National Cancer Research Centre (CNIO), Madrid E28029, Spain.

2. Telomeres and Telomerase Group, CNIO, Madrid E28029, Spain.

3. Laboratory of Bioactive Products and Metabolic Syndrome, Madrid Institute for Advanced Studies (IMDEA) in Food, CEI UAM+CSIC, Madrid E28049, Spain.

4. Experimental Therapeutics Programme, CNIO, Madrid E28029, Spain.

5. Bioinformatics Unit, CNIO, Madrid E28029, Spain.

6. Histopathology Unit, CNIO, Madrid E28029, Spain.

7. Cell Plasticity and Cancer Group, Vall d’Hebron Institute of Oncology (VHIO), Barcelona E08035, Spain.

Abstract

For cell reprogramming, context matters Differentiated cells in a culture dish can assume a new identity when manipulated to express four transcription factors. This “reprogramming” process has sparked interest because conceivably it could be harnessed as a therapeutic strategy for tissue regeneration. Mosteiro et al. used a mouse model to study the signals that promote cell reprogramming in vivo. They found that the factors that trigger reprogramming in vitro do the same in vivo; however, they also inflict cell damage. The damaged cells enter a state of senescence and begin secreting certain factors that promote reprogramming, including an inflammatory cytokine called interleukin-6. Thus, in the physiological setting, cell senescence may create a tissue context that favors reprogramming of neighboring cells. Science , this issue p. 10.1126/science.aaf4445

Funder

Spanish Association Against Cancer (AECC)

European Regional Development Fund

European Research Council

European Social Fund

Botin Foundation

Banco Santander

Ramon Areces Foundation

AXA Foundation

Publisher

American Association for the Advancement of Science (AAAS)

Subject

Multidisciplinary

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