Identification of a novel gene signature of ES cells self-renewal fluctuation through system-wide analysis

Luigi Cerulo, Daniela Tagliaferri, Pina Marotta, Pietro Zoppoli, Filomena Russo, Claudia Mazio, Mario DeFelice, Michele Ceccarelli, Geppino Falco

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9 Citations (Scopus)

Abstract

Embryonic Stem cells (ESCs) can be differentiated into ectoderm, endoderm, and mesoderm derivatives, producing the majority of cell types. In regular culture conditions, ESCs' self-renewal is maintained through molecules that inhibit spontaneous differentiation enabling long-term cellular expansion. This undifferentiating condition is characterized by multiple metastable states that fluctuate between self-renewal and differentiation balance. Here, we aim to characterize the high-pluripotent ESC metastate marked by the expression of Zscan4 through a supervised machine learning framework based on an ensemble of support vector machine (SVM) classifiers. Our study revealed a leukaemia inhibitor factor (Lif) dependent not-canonical pluripotency signature (AF067063, BC061212, Dub1, Eif1a, Gm12794, Gm13871, Gm4340, Gm4850, Tcstv1/3, and Zfp352), that specifically marks Zscan4 ESCs' fluctuation. This novel ESC metastate is enhanced by highpluripotency culture conditions obtained through Extracellular signal Regulated-Kinase (ERK) and Glycogen synthase kinase- 3 (Gsk-3) signaling inhibition (2i). Significantly, we reported that the conditional ablation of the novel ESC metastate marked by the expression of Gm12794 is required for ESCs self-renewal maintenance. In conclusion, we extend the comprehension of ESCs biology through the identification of a novel molecular signature associated to pluripotency programming. Copyright:

Original languageEnglish
Article number0083235
JournalPloS one
Volume9
Issue number1
DOIs
Publication statusPublished - 2 Jan 2014

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ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • General

Cite this

Cerulo, L., Tagliaferri, D., Marotta, P., Zoppoli, P., Russo, F., Mazio, C., DeFelice, M., Ceccarelli, M., & Falco, G. (2014). Identification of a novel gene signature of ES cells self-renewal fluctuation through system-wide analysis. PloS one, 9(1), [0083235]. https://doi.org/10.1371/journal.pone.0083235