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

Research output: Contribution to journalArticle

8 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
Externally publishedYes

Fingerprint

embryonic stem cells
Embryonic Stem Cells
Stem cells
Genes
genes
cells
Cell culture
Cytology
Glycogen Synthase Kinase 3
Pluripotent Stem Cells
Endoderm
Ectoderm
Cell Self Renewal
artificial intelligence
Extracellular Signal-Regulated MAP Kinases
Mesoderm
Ablation
leukemia
mitogen-activated protein kinase
cell biology

ASJC Scopus subject areas

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

Cite this

Cerulo, L., Tagliaferri, D., Marotta, P., Zoppoli, P., Russo, F., Mazio, C., ... 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

Identification of a novel gene signature of ES cells self-renewal fluctuation through system-wide analysis. / Cerulo, Luigi; Tagliaferri, Daniela; Marotta, Pina; Zoppoli, Pietro; Russo, Filomena; Mazio, Claudia; DeFelice, Mario; Ceccarelli, Michele; Falco, Geppino.

In: PLoS One, Vol. 9, No. 1, 0083235, 02.01.2014.

Research output: Contribution to journalArticle

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, vol. 9, no. 1, 0083235. https://doi.org/10.1371/journal.pone.0083235
Cerulo, Luigi ; Tagliaferri, Daniela ; Marotta, Pina ; Zoppoli, Pietro ; Russo, Filomena ; Mazio, Claudia ; DeFelice, Mario ; Ceccarelli, Michele ; Falco, Geppino. / Identification of a novel gene signature of ES cells self-renewal fluctuation through system-wide analysis. In: PLoS One. 2014 ; Vol. 9, No. 1.
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