Detecting Cellular Senescence in Reprogramming

  • Coralie Cazin
  • Mathieu von Joest
  • Han LiEmail author
Part of the Methods in Molecular Biology book series (MIMB, volume 1896)


Cellular senescence has been suggested to facilitate tissue regeneration via promoting cellular plasticity. Here, we describe multiple systems, both in vitro and in vivo, to detect senescence in the context of cellular reprogramming.

Key words

Cellular senescence Reprogramming Cellular plasticity SA-β-Gal 


  1. 1.
    Baker DJ, Wijshake T, Tchkonia T, LeBrasseur NK, Childs BG, van de Sluis B, Kirkland JL, van Deursen JM (2011) Clearance of p16Ink4a-positive senescent cells delays ageing-associated disorders. Nature 479(7372):232–236. CrossRefPubMedPubMedCentralGoogle Scholar
  2. 2.
    Munoz-Espin D, Canamero M, Maraver A, Gomez-Lopez G, Contreras J, Murillo-Cuesta S, Rodriguez-Baeza A, Varela-Nieto I, Ruberte J, Collado M, Serrano M (2013) Programmed cell senescence during mammalian embryonic development. Cell 155(5):1104–1118. CrossRefGoogle Scholar
  3. 3.
    Serrano M, Lin AW, McCurrach ME, Beach D, Lowe SW (1997) Oncogenic ras provokes premature cell senescence associated with accumulation of p53 and p16INK4a. Cell 88(5):593–602CrossRefGoogle Scholar
  4. 4.
    Liu D, Hornsby PJ (2007) Senescent human fibroblasts increase the early growth of xenograft tumors via matrix metalloproteinase secretion. Cancer Res 67(7):3117–3126. CrossRefPubMedGoogle Scholar
  5. 5.
    van Deursen JM (2014) The role of senescent cells in ageing. Nature 509(7501):439–446. CrossRefPubMedPubMedCentralGoogle Scholar
  6. 6.
    Demaria M, Ohtani N, Youssef SA, Rodier F, Toussaint W, Mitchell JR, Laberge RM, Vijg J, Van Steeg H, Dolle ME, Hoeijmakers JH, de Bruin A, Hara E, Campisi J (2014) An essential role for senescent cells in optimal wound healing through secretion of PDGF-AA. Dev Cell 31(6):722–733. CrossRefPubMedPubMedCentralGoogle Scholar
  7. 7.
    Yun MH, Davaapil H, Brockes JP (2015) Recurrent turnover of senescent cells during regeneration of a complex structure. Elife 4.
  8. 8.
    Abad M, Mosteiro L, Pantoja C, Canamero M, Rayon T, Ors I, Grana O, Megias D, Dominguez O, Martinez D, Manzanares M, Ortega S, Serrano M (2013) Reprogramming in vivo produces teratomas and iPS cells with totipotency features. Nature 502(7471):340–345. CrossRefPubMedGoogle Scholar
  9. 9.
    Takahashi K, Yamanaka S (2006) Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell 126(4):663–676. CrossRefPubMedGoogle Scholar
  10. 10.
    Li H, Collado M, Villasante A, Strati K, Ortega S, Canamero M, Blasco MA, Serrano M (2009) The Ink4/Arf locus is a barrier for iPS cell reprogramming. Nature 460(7259):1136–1139. CrossRefPubMedPubMedCentralGoogle Scholar
  11. 11.
    Chiche A, Le Roux I, von Joest M, Sakai H, Aguin SB, Cazin C, Salam R, Fiette L, Alegria O, Flamant P, Tajbakhsh S, Li H (2017) Injury-induced senescence enables in vivo reprogramming in skeletal muscle. Cell Stem Cell 20(3):407–414 e404. CrossRefPubMedGoogle Scholar
  12. 12.
    Mosteiro L, Pantoja C, Alcazar N, Marion RM, Chondronasiou D, Rovira M, Fernandez-Marcos PJ, Munoz-Martin M, Blanco-Aparicio C, Pastor J, Gomez-Lopez G, De Martino A, Blasco MA, Abad M, Serrano M (2016) Tissue damage and senescence provide critical signals for cellular reprogramming in vivo. Science 354(6315). CrossRefGoogle Scholar
  13. 13.
    Ritschka B, Storer M, Mas A, Heinzmann F, Ortells MC, Morton JP, Sansom OJ, Zender L, Keyes WM (2017) The senescence-associated secretory phenotype induces cellular plasticity and tissue regeneration. Genes Dev 31(2):172–183. CrossRefPubMedPubMedCentralGoogle Scholar
  14. 14.
    Conner DA (2001) Mouse embryo fibroblast (MEF) feeder cell preparation. Curr Protoc Mol Biol Chapter 23:Unit 23 22.
  15. 15.
    Han L, Strati K, Domínguez V, Martín J, Blasco M, Serrano M, Ortega S (2001) Induced pluripotency: generation of iPS cells from mouse embryonic fibroblasts. ISTT manual Chapter 23. doi: Google Scholar
  16. 16.
    Cazin C, Chiche A, Li H (2017) Evaluation of injury-induced senescence and in vivo reprogramming in the skeletal muscle. J Vis Exp (128).

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Cellular Plasticity and Disease Modeling, Department of Developmental and Stem Cell BiologyCNRS UMR 3738, Institut PasteurParisFrance

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